Author: Tsoumani, Marina ; Sprikkelman, Aline B ; Pongracic, Jacqueline A ; Hampel, Frank C ; Johnston, Douglas T ; Burks, A Wesley ; Nilsson, Caroline ; Dorsey, Morna J ; Jones, Stacie M ; Mansfield, Lyndon E ; Vitalpur, Girish ; Casale, Thomas B ; O'B Hourihane, Jonathan ; Sher, Ellen R ; Beyer, Kirsten ; Bird, J Andrew ; Shreffler, Wayne G ; Greiner, Alexander N ; Sharma, Vibha ; Chong, Hey Jin ; Sher, Lawrence ; Sharma, Hemant P ; Jeong, David K ; Kachru, Rita ; Fritz, Stephen B ; Oude Elberink, Joanna N G ; Varshney, Pooja ; du Toit, George ; Lanser, Bruce J ; Carr, Tara F ; Sindher, Sayantani B ; Spergel, Jonathan M ; Portnoy, Jay M ; Yang, William H ; Kim, Edwin H ; Siri, Dareen ; Anagnostou, Aikaterini ; Fernández-Rivas, Montserrat ; Leonard, Stephanie A ; Vereda, Andrea ; Petroni, Daniel H ; Zubeldia, José Manuel ; Assa'ad, Amal H ; Wang, Julie ; Adelman, Daniel C ; Ciaccio, Christina E ; Smith, Alex ; Ibáñez, Maria Dolores ; Carr, Warner W ; Fineman, Stanley M ; Vickery, Brian P ; Maier, Mary C ; Ohayon, Jason A ; Ryan, Robert ; Sanders, Georgiana M ; Rupp, Ned T ; Muraro, Antonella ; Ben-Shoshan, Moshe ; Sussman, Gordon L ; Rachid, Rima ; Greos, Leon S ; Blümchen, Katharina

BACKGROUNDThe randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents.OBJECTIVEARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals.METHODSActive arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non-daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics.RESULTSOverall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n = 256; PTAH-naive, n = 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non-daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non-daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm.CONCLUSIONSContinued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.

27 Nov 2018·JAMAQ1 · MEDICINE

Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks

Q1 · MEDICINE

Article

Author: Shapiro, Ralph ; Davis-Lorton, Mark ; Nothaft, Wolfram ; Riedl, Marc A. ; Schranz, Jennifer ; Martinez-Saguer, Inmaculada ; Li, H. Henry ; Baptista, Jovanna ; Johnston, Douglas T. ; Schwartz, Lawrence B. ; Smith, Andrew M. ; Gierer, Selina ; Zanichelli, Andrea ; Busse, Paula J. ; Staubach, Petra ; Bernstein, Jonathan A. ; Zuraw, Bruce L. ; Soteres, Daniel ; Tachdjian, Raffi ; Shennak, Mustafa ; Craig, Timothy ; Cicardi, Marco ; Manning, Michael E. ; Longhurst, Hilary J. ; Magerl, Markus ; Lumry, William R. ; Maurer, Marcus ; Rehman, Syed M. ; Banerji, Aleena ; Hebert, Jacques ; Anderson, John ; Yang, William H. ; Zaragoza-Urdaz, Rafael H. ; Wedner, H. James ; Jacobs, Joshua

ImportanceCurrent treatments for long-term prophylaxis in hereditary angioedema have limitations.ObjectiveTo assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks.Design, Setting, and ParticipantsPhase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Patients were randomized between March 3, 2016, and September 9, 2016; last day of follow-up was April 13, 2017. Randomization was 2:1 lanadelumab to placebo; patients assigned to lanadelumab were further randomized 1:1:1 to 1 of the 3 dose regimens. Patients 12 years or older with hereditary angioedema type I or II underwent a 4-week run-in period and those with 1 or more hereditary angioedema attacks during run-in were randomized.InterventionsTwenty-six-week treatment with subcutaneous lanadelumab 150 mg every 4 weeks (n = 28), 300 mg every 4 weeks (n = 29), 300 mg every 2 weeks (n = 27), or placebo (n = 41). All patients received injections every 2 weeks, with those in the every-4-week group receiving placebo in between active treatments.Main Outcome and MeasuresPrimary efficacy end point was the number of investigator-confirmed attacks of hereditary angioedema over the treatment period.ResultsAmong 125 patients randomized (mean age, 40.7 years [SD, 14.7 years]; 88 females [70.4%]; 113 white [90.4%]), 113 (90.4%) completed the study. During the run-in period, the mean number of hereditary angioedema attacks per month in the placebo group was 4.0; for the lanadelumab groups, 3.2 for the every-4-week 150-mg group; 3.7 for the every-4-week 300-mg group; and 3.5 for the every-2-week 300-mg group. During the treatment period, the mean number of attacks per month for the placebo group was 1.97; for the lanadelumab groups, 0.48 for the every-4-week 150-mg group; 0.53 for the every-4-week 300-mg group; and 0.26 for the every-2-week 300-mg group. Compared with placebo, the mean differences in the attack rate per month were -1.49 (95% CI, -1.90 to -1.08; P < .001); -1.44 (95% CI, -1.84 to -1.04; P < .001); and -1.71 (95% CI, -2.09 to -1.33; P < .001). The most commonly occurring adverse events with greater frequency in the lanadelumab treatment groups were injection site reactions (34.1% placebo, 52.4% lanadelumab) and dizziness (0% placebo, 6.0% lanadelumab).Conclusions and RelevanceAmong patients with hereditary angioedema type I or II, treatment with subcutaneous lanadelumab for 26 weeks significantly reduced the attack rate compared with placebo. These findings support the use of lanadelumab as a prophylactic therapy for hereditary angioedema. Further research is needed to determine long-term safety and efficacy.Trial RegistrationEudraCT Identifier: 2015-003943-20; ClinicalTrials.gov Identifier: NCT02586805.

100 Deals associated with Clinical Research of Charlotte LLC

100 Translational Medicine associated with Clinical Research of Charlotte LLC

Corporation Tree

Boost your research with our corporation tree data.

view full example data

Pipeline

Pipeline Snapshot as of 26 Apr 2025

No data posted

Deal

Boost your decision using our deal data.

view full example data

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Profit

Explore the financial positions of over 360K organizations with Synapse.

view full example data

Grant & Funding(NIH)

Access more than 2 million grant and funding information to elevate your research journey.

view full example data

Investment

Gain insights on the latest company investments from start-ups to established corporations.

view full example data

Financing

Unearth financing trends to validate and advance investment opportunities.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Clinical Research of Charlotte LLC

Overview

Related

Corporation Tree

Pipeline

Pipeline Snapshot as of 26 Apr 2025

Deal

Translational Medicine

Profit

Grant & Funding(NIH)

Investment

Financing