A Randomized, Double‑Blind, Placebo‑Controlled Phase 2/3 Study of Subcutaneous PF‑07275315 in Adults with Moderate‑to‑Severe Chronic Obstructive Pulmonary Disease

Primary objective: to evaluate the efficacy of PF-07275315 compared with placebo in adult participants with moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD) in Phase 2 (two dose levels) and Phase 3 (single dose regimen), thereby determining the drug’s impact on lung function and exacerbation risk. Secondary objectives: • Phase 2 – to assess the effect of each dose on forced expiratory volume in one second (FEV1) and on the incidence of severe COPD exacerbations; to evaluate safety parameters for both doses. • Phase 3 – to assess improvement in FEV1 and to evaluate health‑related quality of life compared with placebo.

The trial enrolled 738 participants aged 35 to 80 years, inclusive of both female and male individuals, who met predefined criteria for moderate-to-severe COPD. Eligible subjects had a documented COPD diagnosis of at least one year according to GOLD guidelines, a post‑bronchodilator FEV1/FVC ratio < 0.7, and a post‑bronchodilator FEV1 between 30 % and 70 % of predicted. All participants reported a CAT score of ≥15 on at least one pre‑randomization visit and a blood eosinophil count ≥150 cells/µL. Continuous use of standard‑of‑care triple therapy (LABA + LAMA + ICS) for ≥6 months, stable for ≥3 months, was required, with double therapy permitted when ICS was contraindicated. Current or former smokers with a history of ≥10 pack‑years were included; former smokers had abstained for at least six months. A history of at least two moderate or severe COPD exacerbations in the prior 12 months, with at least one treated with systemic corticosteroids and occurring while on triple therapy, was mandatory. Body mass index criteria ranged from 18 to 40 kg/m². Participants were selected through screening visits that verified these clinical and lifestyle parameters, resulting in a population reflective of patients with advanced COPD receiving stable inhaled therapy.

The study is an interventional phase 2/3 trial evaluating the efficacy and safety of PF-07275315 in adults with moderate‑to‑severe Chronic Obstructive Pulmonary Disease. Participants are randomized in a parallel‑group design to receive either two dose levels of the investigational product or matching placebo in a double‑blind, placebo‑controlled manner. After a screening visit to confirm eligibility, eligible subjects undergo a baseline visit, randomization, and initiation of subcutaneous study medication. Subsequent clinic visits occur at weeks 4, 12, 24, 36, and 52 to assess lung function, symptom scores, and safety parameters, with the final visit at week 52 serving as the end‑of‑study assessment. Participant involvement therefore spans approximately one year from first dose to study completion. Early termination may occur if a serious adverse event arises, major protocol violations occur, or the participant withdraws consent. Primary efficacy endpoints include change from baseline in pre‑bronchodilator FEV₁ at week 24 for phase 2 and the annualized rate of moderate or severe exacerbations for phase 3; secondary endpoints assess additional lung‑function measures, health‑questionnaire scores, and safety outcomes.

The investigational product, PF-07275315, is supplied as a solution for injection intended for subcutaneous administration. Each dose consists of 0 mg of the active substance delivered in a single‑use vial. The medication is administered by a subcutaneous injection according to the study‑specified dosing schedule, which may involve multiple administrations over the treatment period. Dosing intervals and the total number of administrations are defined in the protocol and are consistent across all participants receiving the test product.

The comparator is a matching placebo formulated to resemble the investigational solution in appearance and volume. 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 the active and placebo injections are recorded in a dosing log, and site personnel verify compliance through direct observation, documentation of injection times, and periodic review of the log entries. Any deviations from the prescribed schedule are reported according to the trial’s monitoring procedures.

The primary efficacy assessment for Phase 2 consists of the change from baseline in pre‑bronchodilator forced expiratory volume in one second (FEV1) at Week 24 compared with placebo, while Phase 3 primary efficacy is evaluated by the annualized rate of moderate or severe ECOPD.

Key secondary efficacy parameters include:

• Annualized rate of moderate or severe ECOPD (Phase 2).
• Change from baseline in pre‑BD FEV1 at all scheduled time points through Week 24.
• Change from baseline in trough, pre‑ and post‑BD FEV1 at each visit during the treatment period up to Week 24.
• Change from baseline in trough, pre‑ and post‑BD forced vital capacity (FVC), FEV1/FVC ratio, % predicted FEV1, and % predicted FVC at each scheduled visit through Week 24.
• Change from baseline in trough FEV1 responsiveness to bronchodilator at each time point through Week 24.
• Change from baseline in pre‑ and post‑BD FEV1 at Week 12 and Week 52 (Phase 3).
• Proportion of participants achieving ≥4‑point improvement in Saint Georges Respiratory Questionnaire (SGRQ) score at Week 52.
• Proportion of participants achieving ≥2‑point improvement in COPD assessment test (CAT) total score at Week 52.
• Proportion of participants achieving ≥2‑point improvement in Evaluating Respiratory Symptoms in COPD (E‑RS:COPD) total score at Week 52.
• Annualized rate of severe ECOPD and of exacerbations requiring emergency department visit or hospitalization (Phase 3).

Spirometric measurements (pre‑ and post‑bronchodilator FEV1, FVC, and related ratios) are obtained using calibrated spirometers in accordance with ATS/ERS guidelines at baseline and at scheduled visits (e.g., Weeks 4, 12, 24, and 52 as applicable). Trough values are collected immediately prior to dosing. Patient‑reported outcomes (SGRQ, CAT, E‑RS:COPD) are administered at baseline and at Week 52. Efficacy data are analyzed as change from baseline (CFB) for continuous variables and as annualized event rates for exacerbation outcomes, with statistical comparisons made versus placebo.