A Multicenter, Multi-Outbreak, Randomized, Controlled Safety and Efficacy Study of Investigational Therapeutics for the Treatment of Patients With Ebola Virus Disease

Background:
Ebola virus can cause serious illness or death. No medicines are approved to treat it. Researchers need to test new medicines to see if they help people recover from Ebola and are safe to give. They need to test the drugs and compare them in a controlled way. Researchers want to test 4 drugs with people who have Ebola and are in treatment centers.
Objective:
To study the safety and effectiveness of 4 drugs for people with Ebola virus.
Eligibility:
People of any age with Ebola infection who are in treatment centers
Design:
Participants will be screened with questions, medical history, and blood tests.
Participants will be randomly assigned to get 1 of 3 study drugs:
ZMapp by IV over about 4 hours. It will be given 3 times, 3 days apart.
Remdesivir by IV over about 1 hour. It will be given once a day for 10 days.
Mab114 by IV for 30-60 minutes. It will be given 1 time.
REGN-EB3 by IV for about 2 hours. It will be given 1 time.
For at least a week, participants will stay in isolation in a clinic. They will:
Get supportive care and be monitored
Have a small plastic tube (IV) put in an arm vein for several days to give fluids and collect blood.
Get their study drug.
Be monitored for disease signs and drug side effects. They may get medicines for side effects.
Have blood and urine tests.
Participants will stay in the clinic until they finish the study drug and are well enough to leave.
Participants will have 2 follow-up visits over 2 months. They will answer questions and give blood and semen samples.
...

Start Date21 Nov 2018

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

NCT02363322

/ CompletedPhase 1/2IIT

A Multicenter Randomized Safety and Efficacy Study of Putative Investigational Therapeutics in the Treatment of Patients With Known Ebola Infection

Background:
- Ebola is a viral infection that can spread quickly and causes life-threatening disease. Right now there is an Ebola outbreak in many countries in West Africa. There are no approved treatments for Ebola. But possible treatments are being developed. Researchers need to study these treatments to see if they help people get better.
Objective:
- To identify possible Ebola treatments. Also, to learn if adding 1 or more experimental drugs to advanced Ebola care can reduce the risk of death.
Eligibility:
- People who have recently been diagnosed with Ebola, usually by a test called the Polymerase Chain Reaction (PCR), and have been hospitalized in an isolation unit for treatment.
Design:
Participants will be randomly assigned to Group A or B. Both groups will get advanced level care. One group will also get an experimental drug.
Participants may have blood tests. They may have another PCR test.
Researchers will try to learn how the participant got Ebola.
Participants put in the experimental drug group may start taking medicine within 24 hours of enrollment. It may be given by mouth or intravenously. Additional doses may be needed.
Participants may have a series of timed blood tests over the first 24 to 48 hours after they take the medicine.
Blood will be drawn frequently. Other body fluids (urine, stool, vaginal fluid, etc.) may also be collected.
Participants will be followed for up to 60 days. They may be evaluated for any long-term effects of the experimental treatment(s). They may be asked to return for 1 or more outpatient visits.
For consenting participants, follow-up will be extended for up to one full year past Day 58 with contact/visits every 1-3 months to assess for a history of signs or symptoms potentially consistent with late onset of virologic relapse syndrome.

Start Date13 Mar 2015

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

[+2]

NCT02389192

/ WithdrawnPhase 1IIT

A Phase 1a Open-Label Study to Assess the Safety and Pharmacokinetics of a Single ZMappTM Administration in Healthy Adult Volunteers

Background:
- Ebola is a virus that can spread quickly and causes serious disease. It is currently causing an outbreak in West Africa. There are no approved treatments for Ebola. ZMappTM is a new drug made of natural infection-fighting substances. Researchers want to see if it can treat Ebola.
Objective:
- To assess the safety of ZMappTM and how the body processes it. To measure the immune system response to ZMappTM.
Eligibility:
- Healthy people 18 50 years old.
Design:
Participants will be screened with a medical history, physical exam, and blood and urine tests. They will have an electrocardiogram (ECG) to measure heart electrical activity. Small pads will be stuck to the arms, legs, and chest.
Participants will be admitted to the hospital. They will have a physical exam, medication review, and blood samples.
Two intravenous (IV) lines will be placed into separate arm veins. A needle will be used to guide plastic tubing into the veins. One will be used to take blood samples. The other will be used to give the study drug.
Participants will be given drugs to help prevent side effects.
Participants will be given the study drug by IV over 10 12 hours. Participants will be monitored closely and vital signs taken frequently. They may have another ECG.
Blood samples will be taken before, during, and after the infusion.
Participants will stay in the hospital 1 or 2 nights after receiving the drug.
Participants will have several study visits over 90 days after getting the study drug. They will be asked about side effects. They may have a physical exam, and blood may be drawn.

Start Date11 Mar 2015

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

100 Clinical Results associated with Porgaviximab

100 Translational Medicine associated with Porgaviximab

100 Patents (Medical) associated with Porgaviximab

Literatures (Medical) associated with Porgaviximab

01 Mar 2024·The Lancet Infectious Diseases

Effect of anti-Ebola virus monoclonal antibodies on endogenous antibody production in survivors of Ebola virus disease in the Democratic Republic of the Congo: an observational cohort study

Article

Author: Toure, Abdoulaye ; Mukadi-Bamuleka, Daniel ; Formenty, Pierre ; Peeters, Martine ; Kitenge, Richard ; Edidi-Atani, François ; Ayouba, Ahidjo ; Legand, Anaïs ; Dilu-Keti, Angele ; Mbala-Kingebeni, Placide ; Ahuka-Mundeke, Steve ; Nkuba-Ndaye, Antoine ; Pelloquin, Raphael ; Delaporte, Eric ; Muyembe-Tamfum, Jean-Jacques ; Diallo, Mamadou Saliou Kalifa ; Thaurignac, Guillaume ; Tovar-Sanchez, Tamara

BACKGROUNDThe use of specific anti-Ebola virus therapy, especially monoclonal antibodies, has improved survival in patients with Ebola virus disease. We aimed to assess the effect of monoclonal antibodies on anti-Ebola virus antibody responses in survivors of the 2018-20 Ebola outbreak in the Democratic Republic of the Congo.METHODSIn this observational prospective cohort study, participants were enrolled at three Ebola survivor clinics in Beni, Mangina, and Butembo (Democratic Republic of the Congo). Eligible children and adults notified as survivors of Ebola virus disease (ie, who had confirmed Ebola virus disease [RT-PCR positive in blood sample] and were subsequently declared recovered from the virus [RT-PCR negative in blood sample] with a certificate of recovery from Ebola virus disease issued by an Ebola treatment centre) during the 2018-20 Ebola virus disease outbreak were invited to participate in the study. Participants were recruited on discharge from Ebola treatment centres and followed up for 12-18 months depending on recruitment date. Routine follow-up assessments were done at 1, 3, 6, and 12-18 months after inclusion. We collected sociodemographic (age, sex, visit site), clinical (anti-Ebola virus drugs), and laboratory data (RT-PCR and Ct values). The primary outcome was the antibody concentrations against Ebola virus glycoprotein, nucleoprotein, and 40-kDa viral protein antigens over time assessed in all participants. Antibody concentrations were measured by the multiplex immunoassay, and the association between anti-Ebola virus antibody levels and the relevant exposures, such as anti-Ebola virus disease drugs (ansuvimab, REGN-EB3, ZMapp, or remdesivir), was assessed using both linear and logistic mixed regression models. This study is registered at ClinicalTrials.gov, NCT04409405.FINDINGSBetween April 16, 2020, and Oct 18, 2021, 1168 survivors were invited to participate in the Les Vainqueurs d'Ebola cohort study. 787 survivors were included in the study, of whom 358 had data available for antibody responses. 85 (24%) of 358 were seronegative for at least two Ebola virus antigens on discharge from the Ebola treatment centre. The antibody response over time fluctuated but a continuous decrease in an overall linear evolution was observed. Quantitative modelling showed a decrease in nucleoprotein, glycoprotein, and VP-40 antibody concentrations over time (p<0·0001) with the fastest decrease observed for glycoprotein. The probability of being seropositive for at least two antigens after 36 months was 53·6% (95% CI 51·6-55·6) for participants who received ansuvimab, 73·5% (71·5-75·5) for participants who received REGN-EB3, 76·8% (74·8-78·8) for participants who received remdesivir, and 78·5% (76·5-80·5) for participants who received ZMapp.INTERPRETATIONAlmost a quarter of survivors were seronegative on discharge from the Ebola treatment centre and antibody concentrations decreased rapidly over time. These results indicate that monoclonal antibodies might negatively affect the production of anti-Ebola virus antibodies in survivors of Ebola virus disease which could increase the risk of reinfection or reactivation.FUNDINGThe French National Agency for AIDS Research-Emergent Infectious Diseases-The French National Institute of Health and Medical Research, the French National Research Institute for Development, and the European and Developing Countries Clinical Trials Partnership.TRANSLATIONFor the French translation of the abstract see Supplementary Materials section.

13 Oct 2016·New England Journal of MedicineQ1 · MEDICINE

A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection

Q1 · MEDICINE

Article

Author: Beigel, John ; Proschan, Michael A. ; Malvy, Denis ; Tierney, John ; Koopmeiners, Joseph S. ; Sahr, Foday ; Massaquoi, Moses B. F. ; Lane, H. Clifford ; Davey, Richard T. Jr. ; Fauci, Anthony S. ; Nordwall, Jacquie Neuhaus ; Neaton, James ; Dodd, Lori

BACKGROUNDData from studies in nonhuman primates suggest that the triple monoclonal antibody cocktail ZMapp is a promising immune-based treatment for Ebola virus disease (EVD).METHODSBeginning in March 2015, we conducted a randomized, controlled trial of ZMapp plus the current standard of care as compared with the current standard of care alone in patients with EVD that was diagnosed in West Africa by polymerase-chain-reaction (PCR) assay. Eligible patients of any age were randomly assigned in a 1:1 ratio to receive either the current standard of care or the current standard of care plus three intravenous infusions of ZMapp (50 mg per kilogram of body weight, administered every third day). Patients were stratified according to baseline PCR cycle-threshold value for the virus (≤22 vs. >22) and country of enrollment. Oral favipiravir was part of the current standard of care in Guinea. The primary end point was mortality at 28 days.RESULTSA total of 72 patients were enrolled at sites in Liberia, Sierra Leone, Guinea, and the United States. Of the 71 patients who could be evaluated, 21 died, representing an overall case fatality rate of 30%. Death occurred in 13 of 35 patients (37%) who received the current standard of care alone and in 8 of 36 patients (22%) who received the current standard of care plus ZMapp. The observed posterior probability that ZMapp plus the current standard of care was superior to the current standard of care alone was 91.2%, falling short of the prespecified threshold of 97.5%. Frequentist analyses yielded similar results (absolute difference in mortality with ZMapp, -15 percentage points; 95% confidence interval, -36 to 7). Baseline viral load was strongly predictive of both mortality and duration of hospitalization in all age groups.CONCLUSIONSIn this randomized, controlled trial of a putative therapeutic agent for EVD, although the estimated effect of ZMapp appeared to be beneficial, the result did not meet the prespecified statistical threshold for efficacy. (Funded by the National Institute of Allergy and Infectious Diseases and others; PREVAIL II ClinicalTrials.gov number, NCT02363322 .).

01 Jan 2015·Przeglad lekarski

Tobacco against Ebola virus disease.

Review

Author: Budzianowski, Jaromir

The Ebola virus disease (EVD), formerly known as a hemorrhagic fever and discovered in 1976, is dangerous, highly infectious disease with very high mortality. There are no licensed therapeutics against EVD, although a range of medicines and therapies are currently being evaluated. During the 2014 Ebola outbreak, an experimental drug named ZMapp was administered on an emergency basis to seven patients of which five were recovered. Currently, since February 2015, ZMapp is tested in clinical trials. ZMapp is a mixture (named a cocktail) of three chimaeric monoclonal antibodies (mAbs) of IgG class, which bind to three different epitopes on Ebola surface glycoprotein (GP). ZMapp was created by systematic selection of antibodies from two other three-component cocktails--MB-003 and ZMab the components of which were produced by rapid transient expression method in tobacco species of Australian origin--Nicotiana benthamiana. The ZMapp antibodies of pharmaceutical grade are manufactured in green-house grown N.benthamiana according to the cGMP (current Good Manufacturing Practice), using RAMP platform (Rapid Antibody Manufacturing Platform) and MagnICON system, which utilizes transient expression by magnifection method using viral vectors delivered to plant tissue by a bacterium--Agrobacterium tumefaciens. The applied glycosylation mutant of N.benthamiana (delta XTFT) synthesizes human-like, biantennary N-glycans, with terminal N-acetylglucoseamine and without typical of plants, immunogenic sugar epitopes-beta1,2-linked xylose and alpha1,3-linked fucose. Due to an absence of fucose on N-glycans attached to the Fc domains, the plant-produced anti-Ebola mAbs elicited significantly stronger antibody-dependent cellular cytotoxicity (ADCC) than the analogous anti-Ebola mAbs with fucosylated (alpha1,6-linked fucose) N-glycans produced in a mammalian CHO cell line--the basic expression system for the industrial production of recombinant therapeutical glycoproteins. As far as a vaccine against Ebola virus disease is considered, so-called Ebola Immunogenic Complex (EIC) consisting of assembled molecules of a humanized IgG mAb--6D8 specific for Ebola GPI with GP1 fused to the C-terminus of the heavy chains, was obtained by transient expression in N. benthamiana.

100 Deals associated with Porgaviximab

External Link

KEGG	Wiki	ATC	Drug Bank
D10974	-	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hemorrhagic Fever, Ebola	Phase 3	-	Public Health Agency of Canada	-
Hemorrhagic Fever, Ebola	Phase 3	-	Mapp Biopharmaceutical, Inc.	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03719586 (CTgov)	Phase 2/3	Hemorrhagic Fever, Ebola	681	Remdesivir (Arm A: Remdesivir Plus Optimized Standard of Care (oSOC))	(edwlxsdjzf) = ajxhpcaxmh oasylrnynt (whhwhtetkh, ggcnipebfm - irrrwqyuzp) View more	-	08 Sep 2021
				MAb114 (Arm B: MAb114 Plus Optimized Standard of Care (oSOC))	(edwlxsdjzf) = qqokykvfmd oasylrnynt (whhwhtetkh, txfxznznde - sjcjzzbmjt) View more
NCT02363322 (PREVAIL II, CTgov)	Phase 1/2	Hemorrhagic Fever, Ebola	72	A/Current Standard of Care Alone (A/Current Standard of Care Alone)	(wbfzxuibyv) = vwcjawbdls bgllysrhoc (blzdoitnwd, cxzvbhfjem - kbbolrtwbe) View more	-	14 May 2019
				A/Current Standard of Care Alone+B/Current Standard of Care Plus ZMapp (B/Current Standard of Care Plus ZMapp)	(wbfzxuibyv) = emiwwrqfme bgllysrhoc (blzdoitnwd, xsvznzpqit - eapvcsreqd) View more
NCT02363322 (Pubmed \| Br Dent J \| N Engl J Med) Manual	Phase 1/2	Hemorrhagic Fever, Ebola	71	Standard of Care+ZMapp	(lxqyfdbmka) = xrzmcrunls uljqufwbfp (suyobvldks )	Positive	13 Oct 2016
				Standard of Care Alone	(lxqyfdbmka) = plhfiajscs uljqufwbfp (suyobvldks )

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