Phase 1 study designed to evaluate the relative bioavailability of a single dose of a test formulation, DSM265-TPGS 34% SDD powder in comparison with a reference DSM265 25% SDD powder formulation used in early clinical trials.

Start Date03 Oct 2018

Sponsor / Collaborator

MMV Medicines for Malaria Venture

[+1]

PACTR201712002879427 / SuspendedNot ApplicableIIT

Randomized, placebo-controlled, double-blind, three-arm, clinical trial to assess safety, tolerability and protective efficacy of PfSPZ-CVac and PfSPZ Vaccine in 1-12 years old African children naturally exposed to malaria parasites

Start Date01 Mar 2018

Sponsor / Collaborator-

NCT03083847 / CompletedPhase 1IIT

Sanaria PfSPZ Challenge With Pyrimethamine Chemoprophylaxis (PfSPZ-CVac Approach): Phase 1 Dose Escalation Trial to Determine Safety and Development of Protective Efficacy After Exposure to Only Pre-erythrocytic Stages of Plasmodium Falciparum

Background:
People get malaria from bites from infected mosquitos. Researchers are studying a vaccine strategy. They will give people malaria parasites by injecting them with live infectious malaria parasites with antimalarial medications and then see if this strategy prevents malaria infection while off antimalarial medications.
Objective:
To see if combining a high dose of live, infectious malaria parasites (known as Sanaria PfSPZ Challenge) and two FDA approved drugs that kill malaria parasites (pyrimethamine [PYR] OR chloroquine [CQ]) is safe and can provide people protection against malaria.
Eligibility:
Healthy adults ages 18-50 who:
are not pregnant or breastfeeding or planning on becoming pregnant while in the study
are not infected with HIV, Hepatitis B or Hepatitis C
have reliable early morning access to the NIH Clinical Center
are able to come to the outpatient clinic frequently, sometimes daily
have not been diagnosed with malaria within the past 10 years
Design:
Participants will be screened with medical history and physical exam. They will have heart, blood, and urine tests.
Participants will have blood drawn for tests at most visits.
Participants will keep track of their temperature and symptoms during some sections of the study.
Participants will join one part of the study.
Part 1 is one month:
Participants will get the parasites by an injection into a vein on day 1 and receive antimalarial medications.
They will have daily visits on days 7-14
They will take another antimalarial at visits on days 15-17.
The final visit will be on day 29.
Part 2 is seven months:
For the first 3 months, participants will get the parasite injection into a vein for 3 injections in total. Each injection will occur once per month while taking an antimalarial drug.
They will have daily visits on days 7-14 after the first injection, and on days 7-11 after the second and third injection.
They will have a final (fourth) injection around month 6 without any antimalarial medication.
After this fourth injection, participants may have up to 21 daily visits from day 7 after injection until end of study.
Part 3 is one month:
Participants will get the parasites by injection into a vein on day 1 without antimalarial medications.
They will have visits almost every day starting day 7 from injection.
They will take an antimalarial medication when they are diagnosed with malaria
They will return for final end of study visit on days 27-29.

Start Date05 Jun 2017

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

[+1]

100 Clinical Results associated with DSM-265

100 Translational Medicine associated with DSM-265

100 Patents (Medical) associated with DSM-265

133

Literatures (Medical) associated with DSM-265

01 Dec 2024·LANCET INFECTIOUS DISEASES

Safety and efficacy of PfSPZ Vaccine against malaria in healthy adults and women anticipating pregnancy in Mali: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials

Article

Author: Issiaka, Djibrilla ; Dicko, Alassane ; Doan, Viyada ; Doritchamou, Justin Y A ; Wang, Jing ; Richie, Thomas L ; Rausch, Kelly M ; Hoffman, Stephen L ; Soumbounou, Ibrahim H ; Kc, Natasha ; Billingsley, Peter F ; Traore, Seydou ; Dolo, Amagana ; Mwakingwe-Omari, Agnes ; Gaoussou, Santara ; Fried, Michal ; Duffy, Patrick E ; Mahamar, Almahamoudou ; Sim, B Kim Lee ; Murshedkar, Tooba ; Attaher, Oumar ; Hu, Zonghui ; Diawara, Halimatou ; Healy, Sara A ; Diallo, Aye ; Morrison, Robert D ; Zaidi, Irfan ; Zeguime, Amatigue ; Mohan, Rathy ; Wylie, Blair J

BACKGROUND:

Plasmodium falciparum parasitaemia during pregnancy causes maternal, fetal, and infant mortality. Poor pregnancy outcomes are related to blood-stage parasite sequestration and the ensuing inflammatory response in the placenta, which decreases over successive pregnancies. A radiation-attenuated, non-replicating, whole-organism vaccine based on P falciparum sporozoites (PfSPZ Vaccine) has shown efficacy at preventing infection in African adults. Here, we aimed to examine vaccine safety and efficacy of the PfSPZ Vaccine in adults and women who anticipated conception.

METHODS:

Two randomised, double-blind, placebo-controlled trials (phase 1 MLSPZV3 and phase 2 MLSPZV4) were conducted at a clinical research centre in Mali. MLSPZV3 included adults aged 18-35 years and MLSPZV4 included non-pregnant women aged 18-38 years who anticipated conception within a year of enrolment. In MLSPZV3, participants were stratified by village and randomly assigned (2:1) using block randomisation to receive three doses of 9 × 10⁵ PfSPZ Vaccine or saline placebo at weeks 0, 1, and 4 (4-week schedule) or at weeks 0, 8, and 16 (16-week schedule) and a booster dose around 1 year later. In MLSPZV4, women received presumptive artemether-lumefantrine twice per day for 3 days 2 weeks before dose one and were randomly assigned (1:1:1) using block randomisation to receive three doses of 9 × 10⁵ or 1·8 × 10⁶ PfSPZ Vaccine or saline placebo all administered at weeks 0, 1, and 4 (4-week schedule). Participants in both studies received artemether-lumefantrine 2 weeks before dose three and additionally 2 weeks before dose four (booster dose) in MLSPZV3. Investigators and participants were masked to group assignment. The primary outcome, assessed in the as-treated population, was PfSPZ Vaccine safety and tolerability within 7 days after each dose. The secondary outcome, assessed in the modified intention-to-treat population, was vaccine efficacy against P falciparum parasitaemia (defined as the time-to-first positive blood smear) from dose three until the end of transmission season. In exploratory analyses, MLSPZV4 evaluated incidence of maternal obstetric and neonatal outcomes as safety outcomes, and vaccine efficacy against P falciparum parasitaemia during pregnancy (defined as time-to-first positive blood smear post-conception). In MLSPZV4, women were followed at least once a month with human chorionic gonadotropin testing, and those who became pregnant received standard of care (including intermittent presumptive sulfadoxine-pyrimethamine antimalarial drugs after the first trimester) during routine antenatal visits. These studies are registered with ClinicalTrials.gov, NCT03510481 and NCT03989102.

FINDINGS:

Participants were enrolled for vaccination during the onset of malaria seasons for two sequential studies conducted from 2018 to 2019 for MLSPZV3 and from 2019 to 2021 for MLSPZV4, with follow-up during malaria seasons across 2 years. In MLSPZV3, 478 adults were assessed for eligibility, of whom 220 were enrolled between May 30 and June 12, 2018, and then between Aug 13 and Aug 18, 2018, and 210 received dose one. 66 (96%) of 69 participants who received the 16-week schedule and 68 (97%) of 70 who received the 4-week schedule of the 9 × 10⁵ PfSPZ Vaccine and 70 (99%) of 71 who received saline completed all three doses in year 1. In MLSPZV4, 407 women were assessed for eligibility, of whom 324 were enrolled from July 3 to July 27, 2019, and 320 received dose one of presumptive artemether-lumefantrine. 300 women were randomly assigned with 100 per group (PfSPZ Vaccine 9 × 10⁵, 1·8 × 10⁶, or saline) receiving dose one. First trimester miscarriages were the most commonly reported serious adverse event but occurred at a similar rate across study groups (eight [15%] of 54 with 9 × 10⁵ PfSPZ Vaccine, 12 [21%] of 58 with 1·8 × 10⁶ PfSPZ Vaccine, and five [12%] of 43 with saline). One unrelated maternal death occurred 425 days after the last vaccine dose in the 1·8 × 10⁶ PfSPZ Vaccine group due to peritonitis shortly after childbirth. Most related adverse events reported in MLSPZV3 and MLSPZV4 were mild (grade 1) and frequency of adverse events in the PfSPZ Vaccine groups did not differ from that in the saline group. Two unrelated serious adverse events occurred in MLSPZV3 (one participant had appendicitis in the 9 × 10⁵ PfSPZ Vaccine group and the other in the saline group died due to a road traffic accident). In MLSPZV3, the 9 × 10⁵ PfSPZ Vaccine did not show vaccine efficacy against parasitaemia with the 4-week (27% [95% CI -18 to 55] in year 1 and 42% [-5 to 68] in year 2) and 16-week schedules (16% [-34 to 48] in year 1 and -14% [-95 to 33] in year 2); efficacies were similar or worse against clinical malaria compared with saline. In MLSPZV4, the PfSPZ Vaccine showed significant efficacy against parasitaemia at doses 9 × 10⁵ (41% [15 to 59]; p=0·0069 in year 1 and 61% [36 to 77]; p=0·0011 in year 2) and 1·8 × 10⁶ (54% [34 to 69]; p<0·0001 in year 1 and 45% [13 to 65]; p=0·029 in year 2); and against clinical malaria at doses 9 × 10⁵ (47% [20 to 65]; p=0·0045 in year 1 and 56% [22 to 75]; p=0·0081 in year 2) and 1·8 × 10⁶ (48% [22 to 65]; p=0·0013 in year 1 and 40% [2 to 64]; p=0·069 in year 2). Vaccine efficacy against post-conception P falciparum parasitaemia during first pregnancies that arose in the 2-year follow-up was 57% (14 to 78; p=0·017) in the 9 × 10⁵ PfSPZ Vaccine group versus 49% (3 to 73; p=0·042) in the 1·8 × 10⁶ PfSPZ Vaccine group. Among 55 women who became pregnant within 24 weeks after dose three, vaccine efficacy against parasitaemia was 65% (23 to 84; p=0·0088) with the 9 × 10⁵ PfSPZ Vaccine and 86% (64 to 94; p<0·0001) with the 1·8 × 10⁶ PfSPZ Vaccine. When combined in a post-hoc analysis, women in the PfSPZ Vaccine groups had a non-significantly reduced time-to-first pregnancy after dose one compared with those in the saline group (log-rank test p=0·056). Exploratory maternal obstetric and neonatal outcomes did not differ significantly between vaccine groups and saline.

INTERPRETATION:

PfSPZ Vaccine was safe and well tolerated in adults in Mali. The 9 × 10⁵ and 1·8 × 10⁶ doses of PfSPZ Vaccine administered as per the 4-week schedule, which incorporated presumptive antimalarial treatment before the first vaccine dose, showed significant efficacy against P falciparum parasitaemia and clinical malaria for two malaria transmission seasons in women of childbearing age and against pregnancy malaria. PfSPZ Vaccine without presumptive antimalarial treatment before the first vaccine dose did not show efficacy.

FUNDING:

National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Sanaria.

01 Oct 2024·JOURNAL OF INFECTION

Antibodies to PfEMP1 and variant surface antigens: Protection after controlled human malaria infection in semi-immune Kenyan adults

Article

Author: Kapulu, Melissa C. ; Abdi, Abdirahman I ; Kinyanjui, Samson M. ; Andisi, Cheryl ; Kapulu, Melissa C ; Kapulu, Melisa C. ; Kinyua, Ann W ; Kimingi, Hannah W ; Sim, B Kim Lee ; Turner, Louise ; Lavstsen, Thomas ; Bejon, Philip ; Kinyanjui, Samson M ; Mwai, Kennedy ; Sim, B. Kim Lee ; Abdi, Abdirahman I. ; Mwikali, Kioko ; Kimingi, Hannah W. ; Kinyua, Ann W.

OBJECTIVES:

Acquisition of antibodies to Plasmodium falciparum variant surface antigens (VSA) expressed on infected red blood cells (iRBCs) is associated with naturally acquired immunity to malaria. We have previously shown that antibodies to VSA on iRBCs are associated with protection against parasite growth in the context of controlled human malaria infection (CHMI). This study explored whether antibodies to recombinant antigens derived from PfEMP1 domains were independently associated with protection during CHMI in semi-immune Kenyan adults.

METHODS:

We used a multiplex bead assay to measure levels of IgG antibody against a panel of 27 recombinant PfEMP1 antigens derived from the PfEMP1 repertoire of the 3D7 parasite clone. We measured IgG levels in plasma samples collected from the CHMI participants before inoculation with Sanaria® PfSPZ Challenge, on the day of diagnosis, and 35 days post-inoculation. Univariable and multivariable Cox regression analysis was used to evaluate the relationship between the levels of antibodies to the antigens and CHMI outcome. We also adjusted for previous data including antibodies to VSA on iRBCs, and we assessed the kinetics of antibody acquisition to the different PfEMP1 recombinant antigens over time.

RESULTS:

All study participants had detectable antibodies to multiple PfEMP1 proteins before inoculation. All PfEMP1 antigens were associated with protection against parasite growth to the threshold criteria for treatment in CHMI, albeit with substantial collinearity. However, individual PfEMP1 antigens were not independently associated with protection following adjustment for breadth of reactivity to VSA on iRBCs and schizont extract. In addition, antibodies to PfEMP1 antigens derived from group B PfEMP1 were induced and sustained in the participants who could not control parasite growth.

CONCLUSION:

This study shows that the breadth of antibody response to VSA on iRBCs, and not to specific PfEMP1 antigens, is predictive of protection against malaria in CHMI.

10 Jun 2024·JCI Insight

Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine

Article

Author: Upadhye, Aditi ; Simpson, Edward ; Little, Morgan R ; Schmidt, Nathan W ; Oneko, Martina ; Steinhardt, Laura C ; Gaskin, Erik L ; Polidoro, Rafael B ; Yamamoto, Ayako ; Liu, Xiaowen ; Oblak, Adrian L ; Bhardwaj, Jyoti ; Hoffman, Stephen L ; Fusco, Elizabeth M ; Haining, W Nicholas ; Otieno, Kephas ; Richie, Thomas L ; Kariuki, Simon ; Senkpeil, Leetah ; Flynn, Barbara J ; Xuei, Xiaoling ; Sim, B Kim Lee ; Murshedkar, Tooba ; Yates, Kathleen B ; Holla, Prasida ; Wiegand, Ryan E ; Swanson, Phillip A ; Seder, Robert A ; Sather, D Noah ; Gao, Hongyu ; Liu, Yunlong ; Macklin, Michael D ; Tran, Tuan M ; Bi, Kevin

A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole-sporozoite PfSPZ vaccine in African infants. Innate immune activation and myeloid signatures at prevaccination baseline correlated with protection from P. falciparum parasitemia in placebo controls. These same signatures were associated with susceptibility to parasitemia among infants who received the highest and most protective PfSPZ vaccine dose. Machine learning identified spliceosome, proteosome, and resting DC signatures as prevaccination features predictive of protection after highest-dose PfSPZ vaccination, whereas baseline circumsporozoite protein-specific (CSP-specific) IgG predicted nonprotection. Prevaccination innate inflammatory and myeloid signatures were associated with higher sporozoite-specific IgG Ab response but undetectable PfSPZ-specific CD8+ T cell responses after vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against infection by sporozoite injection in malaria-naive mice while diminishing the CD8+ T cell response to radiation-attenuated sporozoites. These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity by whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8+ T cell responses suggests that PfSPZ vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways.

News (Medical) associated with DSM-265

14 Aug 2024

·www.drugs.com

Candidate Malaria Vaccine Provides Lasting Protection in NIH-Sponsored Trials

August 14, 2024 -- Two National Institutes of Health (NIH)-supported trials of an experimental malaria vaccine in healthy Malian adults found that all three tested regimens were safe. One of the trials enrolled 300 healthy women ages 18 to 38 years who anticipated becoming pregnant soon after immunization. That trial began with drug treatment to remove malaria parasites, followed by three injections spaced over a month of either saline placebo or the investigational vaccine at one of two dosages. Both dosages of the vaccine candidate conferred a significant degree of protection from parasite infection and clinical malaria that was sustained over a span of two years without the need for a booster dose—a first for any malaria vaccine. In an exploratory analysis of women who conceived during the study, the vaccine significantly protected them from malaria in pregnancy. If confirmed through additional clinical trials, the approach modeled in this study could open improved ways to prevent malaria in pregnancy. Spread by Anopheles mosquitoes, malaria parasites, including those of the species Plasmodium falciparum ( Pf ), can cause illness in people of any age. However, pregnant women, infants and very young children are especially vulnerable to life-threatening disease. Malarial parasitemia in pregnancy is estimated to cause up to 50,000 maternal deaths and 200,000 stillbirths in Africa each year. The trials were co-led by investigators from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and the University of Sciences, Techniques and Technologies, Bamako (USTTB), Mali. The investigational vaccine used in both trials was PfSPZ Vaccine, a radiation-attenuated vaccine based on Pf sporozoites (a stage of the parasite’s lifecycle), manufactured by Sanaria Inc., Rockville, Maryland. Multiple previous clinical trials of PfSPZ Vaccine have shown it to be safe, including in malaria-endemic countries such as Mali. In results published in 2022, for example, an NIAID-sponsored, placebo-controlled trial of a three-dose regimen of PfSPZ Vaccine in Burkina Faso found that the vaccine had up to 46% efficacy that lasted at least 18 months. In the first year of the current trial, 55 women became pregnant within 24 weeks of the third vaccine dose. Among these women, vaccine efficacy against parasitemia (whether before or during pregnancy) was 65% in those who received the lower dose vaccine and 86% in those who received the higher dose. Among 155 women who became pregnant across both study years, vaccine efficacy was 57% for those who received lower dose vaccine and 49% in those in the higher dosage group. Women who received the investigational vaccine at either of the dosages conceived sooner than those who received placebo, although this finding did not reach the level of statistical significance, reported the investigators. The researchers speculate that the PfSPZ Vaccine might avert malaria-related early pregnancy losses since parasitemia risk during the periconception period was reduced by 65 to 86%. “Preconception immunization is a new strategy to reduce mortality for women with malaria in pregnancy,” the researchers note. They plan to investigate the safety of PfSPZ Vaccine administered during pregnancy, then examine the efficacy of PfSPZ given preconception or during pregnancy in larger clinical trials. “Existing measures are not protecting women from malaria in pregnancy,” they added. “A safe and effective vaccine is urgently needed, and our results indicate PfSPZ Vaccine might be a suitable candidate,” they conclude. The PfSPZ Vaccine Study Team was led by Alassane Dicko, M.D., of the Malaria Research and Training Center (MRTC), USTTB, Mali, Stephen L. Hoffman, M.D., of Sanaria Inc., and Patrick E. Duffy, M.D., of the NIAID Laboratory of Malaria Immunology and Vaccinology. Joint co-first authors were Halimatou Diawara, M.D., of MRTC, and Sara A. Healy, M.D., NIAID. Additional information about the trials is available at clinicaltrials.gov using the identifiers NCT03510481 or NCT03989102. H Diawara et al. Safety and efficacy of PfSPZ Vaccine against malaria in healthy adults and women anticipating pregnancy in Mali: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials . Lancet Infectious Diseases DOI: 10.1016/ S1473-3099(24)00360-8 (2024). Patrick E. Duffy, M.D., Chief, Laboratory of Malaria Immunology and Vaccinology, NIAID, is available to comment. To schedule interviews, please contact Anne A. Oplinger, (301) 402-1663, niaidnews@niaid.nih.gov . NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website . About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov. Source: NIH Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

VaccineClinical ResultPhase 1

04 Jan 2023

·www.sciencedaily.com

A three-dose malaria vaccine shows safety, efficacy in West African adults

A three-dose regimen of a whole-parasite vaccine against malaria -- called Plasmodium falciparum sporozoite (PfSPZ) vaccine -- demonstrated safety and efficacy when tested in adults living in Burkina Faso, West Africa, which has endemic malaria. A three-dose regimen of a whole-parasite vaccine against malaria -- called Plasmodium falciparum sporozoite (PfSPZ) vaccine -- demonstrated safety and efficacy when tested in adults living in Burkina Faso, West Africa, which has endemic malaria. That is the finding of a new study published on Dec. 7, 2022, in Science Translational Medicine. Researchers at the University of Maryland School of Medicine's Center for Vaccine Development and Global Health (CVD) led the work. About 241 million people worldwide were infected with malaria in 2020, and 627,000 people died from their infections. Scientists have tried for decades to develop a highly effective malaria vaccine without much success. That is because the vaccines have been shown not to provide much protection in those who have already been infected with malaria earlier in life due to their acquired immunity. The first vaccine against malaria (RTS,S/AS01) was approved by the World Health Organization in October 2021, and it provides modest protection against malaria. The new study involved 80 participants in a randomized controlled clinical trial comparing three doses of the PfSPZ vaccine against a placebo. At six months follow up, vaccine efficacy was up to 48 percent; at 18 months follow up, vaccine efficacy was up to 46 percent. "Our study shows that the vaccine can be given to malaria-experienced adults in a highly endemic area and still provide protection, which is difficult and complicated as these individuals already have significant immune responses to malaria parasites that must be overcome by a vaccine for it to be successful," said study corresponding author Matthew B. Laurens, MD, MPH, Professor of Pediatrics at UMSOM and Director, International Clinical Trials Unit in the Malaria Research Group at CVD. PfSPZ Vaccine is made with a live-attenuated form of the malaria parasite Plasmodium falciparum sporozoite, which is transmitted by mosquitos. The vaccine is made by Rockville, Maryland-based Sanaria Inc. and has been shown to provide at least 90-percent protection in challenge studies where volunteers are infected with malaria (in a highly controlled way); these studies were conducted by CVD researchers in the U.S. and by other groups in Tanzania. In African adults who previously had malaria, PfSPZ provided 52 percent vaccine efficacy against naturally transmitted malaria infection. Protection lasted 8 to 14 months. In the new study, researchers wanted to reduce the number of required injections from five shots to three, while improving vaccine efficacy. They assessed safety, tolerability, immunogencity, and vaccine efficacy of three injections of the vaccine in a two-part study. The first part enrolled 32 adults in a dose-escalation phase in 2016 and the second enrolled 80 adults in a randomized trial in 2017. In the randomized trial, 39 received PfSPZ Vaccine and 41 received placebo. Study participants were healthy men and non-pregnant women ages 21 to 40. The vaccines were well tolerated and without concerning side effects. "New strategies are needed to achieve the United Nations sustainable development goal of a 90-percent reduction in malaria incidence and mortality by 2030," said UMSOM DeanMark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor. "Innovative vaccines that provide a higher level of protection against malaria are urgently needed to help to achieve this goal." Additional co-authors on the newly published research from UMSOM's Center for Vaccine Development and Global Health include: Kirsten E. Lyke, MD, Professor of Medicine; Sudhaunshu Joshi, MS, Laboratory Specialist; Biraj Shrestha, Laboratory Assistant; and Kathy Strauss, Laboratory Specialis. The new study reflects a long history of malaria vaccine development at UMSOM that started in the early 1970s with landmark research from David Clyde, MD, former head of malarial studies at CVD. His studies demonstrated that high-level protection against malaria infection is possible using a whole organism vaccine. Future research includes conducting additional clinical trials of the PfSPZ Vaccine in groups that would benefit most from vaccine-induced protection, including children, travelers, military personnel, and pregnant women. Many of these studies are underway, including an ongoing trial at UMSOM to administer a compressed schedule of three doses of PfSPZ Vaccine in one month, which is a feasible timeline for travelers and military populations. Results of this study are expected in 2023. The study was funded by NIH's National Institute of Allergy and Infectious Diseases grants U01AI112367 and 5R44AI055229.

Clinical ResultVaccineDrug Approval

26 Jul 2022

·sanaria.com

COLLABORATORS PUBLISH ARTICLE IN NATURE COMMUNICATIONS: PLASMODIUM FALCIPARUM 7G8 CHALLENGE PROVIDES CONSERVATIVE PREDICTION OF EFFICACY OF PFNF54-BASED PFSPZ VACCINE IN AFRICA

ROCKVILLE, MD, USA – July 12, 2022 – Sanaria Inc., University of Maryland School of Medicine, Naval Medical Research Center, National Institutes of Health (USA), University of Bamako Malaria Research and Training Center (Mali), and University of Tübingen (Germany) published results in Nature Communications showing Plasmodium falciparum 7G8 human challenge trials provide a conservative prediction of efficacy of PfNF54-based PfSPZ Vaccine in Africa. The efficacy of malaria vaccines and drugs can be tested by challenging volunteers with live, infectious parasites, a procedure known as Controlled Human Malaria Infection (CHMI). CHMI using the same P. falciparum (Pf) malaria strain as the vaccine, potentially overestimates vaccine efficacy (VE) against the naturally occurring antigenically heterogeneous, variant parasite populations. Consequently, expensive field trials requiring large sample sizes and long duration have been necessary to obtain accurate measures of VE. To counter this, the investigative team increased the stringency of CHMI by selecting a Brazilian isolate, Pf7G8, which is genetically distant from the West African strain (PfNF54) in Sanaria® PfSPZ Vaccine. Using two identical regimens to immunize US and Malian adults, VE over 24 weeks in the field was as good as or better than VE against Pf7G8 CHMI at 24 weeks in the US. To explain this finding, the University of Maryland team quantified differences in the genome, proteome, and predicted CD8 T cell epitopes of PfNF54 relative to Pf7G8 and 704 Pf isolates from Africa. Pf7G8 is genetically more distant from PfNF54 than any of the African isolates. The investigators propose that VE against Pf7G8 CHMI can provide pivotal data for malaria vaccine licensure for travelers to Africa, and potentially for endemic populations, because the genetic distance of Pf7G8 from PfNF54 makes it a stringent surrogate for naturally occurring Pf parasites in Africa. Prof. Claire Fraser, the Dean’s Endowed Professor of Medicine at the University of Maryland School of Medicine (UMSOM) and Director of the Institute for Genome Sciences, University of Maryland, School of Medicine, commented, “This study clearly highlights the importance of integrating genomics and computational biology into the development plan for vaccines against the highly complex and genetically variant parasites that cause malaria.” “This study offers important insights into the potential power of CHMI for accelerating malaria vaccine development,” said Dr. Peter McElroy, Malaria Branch Chief, U.S. Centers for Disease Control and Prevention. “It can inform the assessment of future vaccines slated for use in Africa and worldwide, to provide better predictability and possibly shorten development timelines.” Forward Looking Statement Except for historical information, this news release contains certain forward-looking statements that involve known and unknown risk and uncertainties, which may cause actual results to differ materially from any future results, performance or achievements expressed or implied by the statements made. Such statements include the availability of an effective vaccine, the expectations for conquering malaria, beliefs concerning the suitability of a successful vaccine, and the establishment of a path toward prevention of infection. These forward-looking statements are further qualified by important factors that could cause actual results to differ materially from those in the forward-looking statements. For business information please email Alexander Hoffman at sanaria@sanaria.com, 301-339-0092. Click here for a link for the Nature Communications article. To download the press release, use this link.

VaccineClinical StudyClinical Result

100 Deals associated with DSM-265

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Malaria, Falciparum	Phase 2	PE	MMV Medicines for Malaria Venture	01 Jan 2016
Malaria, Vivax	Phase 2	PE	MMV Medicines for Malaria Venture	01 Jan 2016
Malaria	Phase 2	AU	Q-Pharm Pty Ltd.	01 Feb 2015
Malaria	Phase 2	AU	Clinical Network Services Pty Ltd.	01 Feb 2015
Parasitemia	Phase 1	BE	MMV Medicines for Malaria Venture	19 Feb 2020
Quartan malaria	Phase 1	US	MMV Medicines for Malaria Venture	01 Mar 2016
Acinetobacter Baumannii Infection	Preclinical	US	The NewYork-Presbyterian Healthcare System, Inc.	13 Dec 2022

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02573857 \| NCT02389348 (Pubmed \| J Antimicrob Chemother)	Phase 1/2	Malaria, Falciparum	-	OZ439 800mg + DSM265 450mg	tfktnsezyz(orkdbaftvj) = pckjssrdym tyxgjwwpyv (pehpsgmmco )	-	28 Jun 2021
NCT02450578 (CTgov)	Phase 1	Malaria, Falciparum	22	Placebo to DSM265 400 mg+DSM265 400mg (Cohort 1a: DSM265/Placebo, Sporozoite Inoculum)	dmisifziog(vvmzyuxwaq) = kqtegcyndh wygvbswzvt (oobnthcevv, pnbkkvcqlz - fjscbyisuu)	-	03 Dec 2020
				Placebo to DSM265 400 mg+DSM265 400mg (Cohort 2: DSM265/Placebo, Sporozoite Inoculum)	dmisifziog(vvmzyuxwaq) = vlkrffkpcz wygvbswzvt (oobnthcevv, uwkslwqfrw - jngiwkvpul)
NCT02573857 (DSMOZ-2, CTgov)	Phase 1/2	Malaria	16	DSM265 (DSM265 P. Falciparum)	hkudpwcgaa(iyaxoeivqi) = fyglzsojkp chqouffyzy (xceqyuvltr, faurehdego - mclqusxlrl) View more	-	05 Jun 2020
				OZ439 (OZ439 P. Vivax)	hkudpwcgaa(iyaxoeivqi) = wbgkmvkvnn chqouffyzy (xceqyuvltr, ofexdkrcpw - pbrhnhmkwd) View more
NCT03637517 (CTgov)	Phase 1	Malaria	42	DSM265 25% SDD, 400 mg fasted (DSM265 25% SDD, 400 mg Fasted)	vbwyivgrlf(cdvyaorteq) = alxisyyorq ewfvrxkvlo (vxnqerrgtr, kdzsewtnzp - jaqiucfrlr) View more	-	11 Mar 2020
				DSM265-TPGS 34% SDD, 400 mg fasted (DSM265-TPGS 34% SDD, 400 mg Fasted)	vbwyivgrlf(cdvyaorteq) = znlxduofwu ewfvrxkvlo (vxnqerrgtr, jhkqpcaykx - msuncampab) View more
NCT02389348 (Pubmed \| Antimicrob Agents Chemother) Manual	Phase 1/2	Malaria, Falciparum	13	Artefenomel+DSM265 (Cohort 1)	rzbgzyrimy(lrtkgupmbg) = kamzrldcou delandqcui (jnjicbetet ) View more	Positive	20 Dec 2019
				Artefenomel+DSM265 (Cohort 2)	rzbgzyrimy(lrtkgupmbg) = jootdeyjml delandqcui (jnjicbetet ) View more

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