Phase 3b/4 Randomized Double‑Blind Study of Depemokimab 100 mg SC Q26 weeks vs Placebo on Exacerbations and Lung‑Function Decline in Adults/Adolescents with Type 2 Asthma

The primary objective is to assess the efficacy of depemokimab 100 mg administered subcutaneously every 26 weeks as add‑on therapy compared with placebo in adults and adolescents with type‑2 asthma who remain at risk of exacerbations despite inhaled corticosteroid/long‑acting β2‑agonist treatment; the outcome is reduction in exacerbation rate, a clinically relevant measure of disease burden. Secondary objectives include:

• evaluation of the proportion of participants achieving clinical remission under depemokimab versus placebo;
• assessment of the impact on quality of life in the subgroup with uncontrolled asthma at baseline;
• determination of the effect on asthma control in the same uncontrolled subgroup;
• exploration of changes in lung function with depemokimab compared with placebo.

The trial enrolled 259 participants diagnosed with asthma who were at least 12 years of age, including both male and female individuals; enrollment of adults only (≥18 years) was permitted in regions where local regulations required it. Eligible participants had a documented physician diagnosis of asthma for ≥2 years, a history of at least two exacerbations in the preceding three years (with one occurring in the year before screening), and were receiving stable low‑ to medium‑dose inhaled corticosteroid/long‑acting β‑agonist therapy for a minimum of three months prior to screening. All participants demonstrated type‑2 (T2) inflammatory disease, defined by peripheral blood eosinophil counts (≥500 cells/µL or ≥300 cells/µL with FeNO ≥35 ppb) or documented chronic rhinosinusitis with nasal polyps. The study population comprised generally healthy individuals apart from their asthma, with no specific dietary or physical‑activity restrictions imposed beyond adherence to their standard asthma regimen. Inclusion required the ability to provide informed consent/assent and, for females of child‑bearing potential, appropriate contraceptive measures; vulnerable subjects were permitted under these conditions.

The MODIFY Study is a Phase 5, multicentre, randomized, double-blind, placebo-controlled trial evaluating add‑on therapy with depemokimab 100 mg administered subcutaneously every 26 weeks in participants with asthma at risk of exacerbations. The protocol defines a treatment and follow‑up period of up to 156 weeks. Study visits are scheduled as follows: a screening visit to confirm eligibility; a baseline/randomization visit; dosing and assessment visits at weeks 0, 26, 52, 78, 104, 130 and 156; and an end‑of‑study visit at week 156. Each visit includes safety monitoring, lung‑function testing, and patient‑reported outcome questionnaires. Participants are expected to remain in the study for the full 156‑week duration unless discontinued per protocol. The primary endpoint is the annualized rate of clinically significant exacerbations; secondary endpoints comprise clinical remission at 104 weeks, changes in quality‑of‑life scores, ACQ‑5 scores, and post‑bronchodilator and pre‑bronchodilator FEV₁ values.

The investigational product, EXDENSUR 100 mg solution for injection in a pre‑filled syringe, contains the monoclonal antibody depemokimab as the sole active substance. It is supplied as a sterile solution for injection, intended for subcutaneous administration at a dose of 100 mg per injection. Doses are administered once every 26 weeks throughout the study period.

The comparator is a sterile 0.9 % (w/v) sodium chloride solution provided in a single‑use pre‑filled syringe, serving as a matching placebo. The placebo contains no active pharmaceutical ingredient and is administered by the same subcutaneous route and schedule as the active product to maintain blinding.

Both investigational and placebo injections are performed by qualified study personnel in a clinical setting. Dosing intervals are recorded in the electronic case report form, and adherence is monitored through site visit logs and participant diaries. Administration timing is verified against the protocol‑specified window of ±7 days for each 26‑week interval.

The primary efficacy assessment will be the annualized rate of clinically significant exacerbations recorded throughout the treatment period, which may extend up to 156 weeks. Exacerbation events will be documented at each study visit and entered into the trial database for rate calculation.

Secondary efficacy evaluations will be performed at baseline and at 104 weeks (2 years). Clinical remission is defined by the simultaneous achievement of four criteria: absence of clinically significant asthma exacerbations during the first 2 years, no use of maintenance oral corticosteroids at 2 years, well‑controlled asthma based on an ACT score of ≥ 20, and no deterioration of lung function, defined as a post‑bronchodilator FEV1 reduction of > 0 mL from baseline. Additional secondary measures include:

• Change from baseline in the AQLQ total overall score at 2 years for participants with baseline ACQ‑5 ≥ 1.5.
• Change from baseline in the ACQ-5 score at 2 years for participants with baseline ACQ‑5 ≥ 1.5.
• Change from baseline in post‑bronchodilator FEV1 at 2 years.
• Change from baseline in pre‑bronchodilator FEV1 at 2 years.

Questionnaire‑based outcomes (ACT, AQLQ, ACQ‑5) will be administered using validated paper or electronic forms at each scheduled visit. Spirometric measurements of post‑ and pre‑bronchodilator FEV1 will be performed according to ATS/ERS standards at baseline and week 104. All data will be analyzed using appropriate statistical models to compare the depemokimab and placebo arms.