Rademikibart Treatment for Moderate-to-Severe, Uncontrolled Asthma: A Phase 2B Randomized Trial

Abstract

Rationale: Rademikibart (formerly CBP-201) is an IL-4Rα-targeting antibody.

Objectives: To evaluate rademikibart in adults with moderate-to-severe, persistent, uncontrolled asthma.

Methods: In this global phase 2b trial (NCT04773678), 322 patients were randomized 1:1:1 to two rademikibart groups (150 mg or 300 mg every other week, following a 600 mg loading dose) or placebo, administered subcutaneously, for 24 weeks.

Measurements and main results: Prebronchodilator (trough) forced expiratory volume in the first second of expiration (FEV₁) at Week 12 (primary endpoint) improved with rademikibart 150 mg and 300 mg: least squares mean changes (95% CI), above placebo, were +140 mL (+44-236 mL; p=0.005) and +189 mL (+92-286 mL; p<0.001), respectively. Prebronchodilator trough FEV₁ improvements occurred rapidly during Week 1, were sustained through Week 24, and greatest in patients with high baseline blood eosinophils (patients with ≥300 eosinophils/mL experienced placebo-adjusted FEV₁ improvement at Week 24 of +420 mL [95% CI, +239-600 mL] in the 300 mg group). Rapid and sustained statistically significant improvements were also observed in percent predicted FEV₁ and Asthma Control Questionnaire score across 24 weeks. Through Week 24, proportions of patients with ≥1 exacerbation were 7.5% (150 mg) and 9.3% (300 mg) vs 16.7% (placebo). 88% of patients completed treatment. Treatment-emergent adverse events (TEAEs) were generally similar to placebo, and no eosinophilia was observed. Injection site reactions were mostly mild. The most common TEAEs (10-12% of patients) were cough, COVID-19, and dyspnea.

Conclusions: Rapid and sustained improvements in lung function and asthma control were gained across 24 weeks of rademikibart therapy. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). Clinical trial registration available at www.

Clinicaltrials: gov, ID: NCT04773678.

Keywords: CBP-201; IL-4Rα; asthma; rademikibart.

Figure 1.

Patient disposition. All patients received at least one dose of study treatment. Q2W = every 2 weeks.

Figure 2.

Change from baseline in prebronchodilator FEV₁ (A) at Week 12 and (B) across 24 weeks of treatment. Full analysis set. Error bars indicate SE. (A) Analysis of covariance model. (B) *P < 0.05, **P < 0.01, and ***P < 0.001 versus placebo. ^†LS mean differences from baseline at Week 24. Mixed model for repeated measures. LS = least squares; n = number of patients with data at Week 12; N = total number of patients with data; Q2W = every 2 weeks.

Figure 3.

Forest plot of change from baseline in prebronchodilator FEV₁ at Week 12 of treatment: full analysis population and subgroups. Analysis of covariance model. CI = confidence interval; Fe_NO = fractional exhaled nitric oxide; LS = least squares; n = number of patients with data at Week 12; ppb = parts per billion; Q2W = every 2 weeks.

Figure 4.

Asthma exacerbations (A) cumulative incidence and (B) rate per year. Exacerbation was defined as hospitalization or urgent medical care due to asthma, treatment with approximately four times the patient’s normal dose of inhaled corticosteroids, or treatment with systemic steroids. Population asthma exacerbation rate is calculated as total number of asthma exacerbations while patients were on treatment divided by the total duration of treatment in years. N = total number of patients with data; Q2W = every 2 weeks.

Figure 5.

Asthma Control Questionnaire (ACQ-6) outcomes. (A) Change from baseline in the six-item ACQ-6 scores across 24 weeks of treatment in the overall population and (B) proportions of patients with ACQ-6 responses at Week 12 in the ⩾300 eosinophils/μl at baseline subgroup. Statistical analysis of least squares (LS) mean change in ACQ-6 scores: full analysis set, mixed model for repeated measures. Error bars indicate SE. **P < 0.01, and ***P < 0.001 versus placebo. ACQ scores incorporate five patient-reported questions and an FEV₁ categorical variable. There is no albuterol component to the score. N = total number of patients with data. ^†LS mean differences from baseline at Week 24. ^‡Post hoc analyses were not statistically analyzed. Q2W = every 2 weeks.