Efficacy and Safety of Pacritinib vs Placebo for Patients With Severe COVID-19: A Phase 2 Randomized Clinical Trial.
JAMA Netw Open
california; st jude; covid-19; Adult; Humans; Male; Middle Aged; COVID-19 Drug Treatment; Interleukin-6; Janus Kinase Inhibitors; Pyrimidines; SARS-CoV-2; Female; Young Adult; Aged; Aged, 80 and over
IMPORTANCE: The morbidity and mortality associated with COVID-19 remain high despite advances in standard of care therapy, and the role of anti-inflammatory agents that inhibit the interleukin 6/JAK2 pathway is still being elucidated.
OBJECTIVE: To evaluate the efficacy and safety of the oral JAK2/IRAK1 inhibitor pacritinib vs placebo in the treatment of adults with severe COVID-19.
DESIGN, SETTING, AND PARTICIPANTS: This phase 2, double-blind, placebo-controlled, randomized clinical trial enrolled hospitalized adult patients with severe COVID-19 at 21 centers across the US between June 2020 and February 2021, with approximately 1.5 months of safety follow-up per patient. Data analysis was performed from September 2021 to July 2022.
INTERVENTIONS: Patients were randomized 1:1 to standard of care plus pacritinib (400 mg per os on day 1 followed by 200 mg twice daily on days 2-14) vs placebo, for 14 days.
MAIN OUTCOMES AND MEASURES: The primary end point was death or need for invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) by day 28. All-cause mortality and safety were also assessed.
RESULTS: A total of 200 patients were randomized to pacritinib (99 patients; 56 men [56.6%]; median [range] age, 60 [19-87] years) or placebo (101 patients; 64 men [63.4%]; median [range] age 59 [28-94] years). The percentage requiring supplementary oxygen was 99.0% (98 patients) in the pacritinib group vs 98.0% (99 patients) in the placebo group. The percentage who progressed to IMV, ECMO, or death was 17.2% (17 patients) in the pacritinib group vs 22.8% (23 patients) in the placebo group (odds ratio, 0.62; 95% CI, 0.28-1.35; P = .23). Among patients with elevated interleukin 6, the rate was 17.5% (11 of 63 patients) in the pacritinib group vs 30.4% (21 of 96 patients) in the placebo group. The adverse event rate was similar for pacritinib vs placebo (78.1% [75 patients] vs 80.2% [81 patients]), with no excess in infection (14.6% [14 patients] vs 19.8% [20 patients]), bleeding (8.3% [8 patients] vs 10.9% [11 patients]), or thrombosis (8.3% [8 patients] vs 7.9% [8 patients]). Rates of grade 3 or higher adverse events were lower with pacritinib than placebo (29.2% [28 patients] vs 40.6% [41 patients]).
CONCLUSIONS AND RELEVANCE: The study did not meet its primary end point in patients with severe COVID-19. Subgroup analyses may indicate specific populations with hyperinflammation that could benefit from pacritinib, although further clinical trials would be needed to confirm these effects.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04404361.
Cafardi, John; Miller, Carole; Terebelo, Howard; Tewell, Chad; Benzaquen, Sadia; Park, David J; Egan, Pamela; Lebovic, Daniel; Pettit, Kristen; Whitman, Eric; Tremblay, Douglas; Feld, Jonathan; Buckley, Sarah; Roman-Torres, Karisse; Smith, Jennifer; Craig, Adam; and Mascarenhas, John, "Efficacy and Safety of Pacritinib vs Placebo for Patients With Severe COVID-19: A Phase 2 Randomized Clinical Trial." (2022). Articles, Abstracts, and Reports. 6738.