Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria naive to complement inhibition.
Alexander RöthGuang-Sheng HeHongyan TongZenghua LinXiaoqin WangChatree Chai-AdisaksophaJe Hwan LeeAndres BrodskyChattree HantaweepantTeresita E DumagayRoberta Demichelis-GómezPonlapat RojnuckarinJing SunMartin HöglundJun Ho JangAnna GayaFernando SilvaNaoshi ObaraRichard J KellyLeigh BeveridgeSimon BuatoisSammy ChebonBrittany GentilePontus LundbergSasha SreckovicJun-Ichi NishimuraAntonio Maria RisitanoBing HanPublished in: American journal of hematology (2024)
Crovalimab is a novel C5 complement inhibitor that enables rapid and sustained C5 inhibition with subcutaneous, low-volume self-administration every 4 weeks. COMMODORE 2 (NCT04434092) is a global, randomized, open-label, multicenter, phase 3 trial evaluating the non-inferiority of crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria not previously treated with C5 inhibition. C5 inhibitor-naive patients with lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN) were randomized 2:1 to crovalimab or eculizumab. Co-primary efficacy endpoints were proportion of patients with hemolysis control (centrally assessed LDH ≤1.5 × ULN) and proportion with transfusion avoidance. Secondary efficacy endpoints were proportions of patients with breakthrough hemolysis, stabilized hemoglobin, and change in FACIT-Fatigue score. The primary treatment period was 24 weeks. Two hundred and four patients were randomized (135 crovalimab; 69 eculizumab). Crovalimab was non-inferior to eculizumab in the co-primary endpoints of hemolysis control (79.3% vs. 79.0%; odds ratio, 1.0 [95% CI, 0.6, 1.8]) and transfusion avoidance (65.7% vs. 68.1%; weighted difference, -2.8 [-15.7, 11.1]), and in the secondary efficacy endpoints of breakthrough hemolysis (10.4% vs. 14.5%; weighted difference, -3.9 [-14.8, 5.3]) and hemoglobin stabilization (63.4% vs. 60.9%; weighted difference, 2.2 [-11.4, 16.3]). A clinically meaningful improvement in FACIT-Fatigue score occurred in both arms. Complete terminal complement activity inhibition was generally maintained with crovalimab. The safety profiles of crovalimab and eculizumab were similar with no meningococcal infections. Most patients who switched from eculizumab to crovalimab after the primary treatment period preferred crovalimab. These data demonstrate the positive benefit-risk profile of crovalimab.
Keyphrases
- open label
- phase iii
- double blind
- phase ii
- placebo controlled
- clinical trial
- red blood cell
- study protocol
- magnetic resonance
- phase ii study
- blood pressure
- sleep quality
- end stage renal disease
- obstructive sleep apnea
- atrial fibrillation
- newly diagnosed
- cardiac surgery
- chronic kidney disease
- contrast enhanced
- network analysis
- squamous cell carcinoma
- radiation therapy
- cross sectional
- gestational age
- sickle cell disease
- electronic health record
- machine learning
- prognostic factors
- physical activity
- smoking cessation