| Protocol No: | ECCT/23/06/04 | Date of Protocol: | 09-11-2022 |
| Study Title: |
A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ASTEGOLIMAB IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE
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| Study Objectives: |
The study objectives are listed below:
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| Laymans Summary: | Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterized by irreversible changes in air flow causing progressive obstruction. The prevalence of diagnosed COPD has dramatically increased over recent years and is among the leading causes of disabilities and mortality. The airflow obstruction among COPD patients is largely linked with long-term morbidity and comorbidities such as hypertension, diabetes, ischemic heart disease, stroke, and heart failures were reported in patients with exacerbated COPD cases. These comorbidities are often linked with smoking, systemic inflammation, airflow limitation, and aging. These comorbidities do not only negatively impact the patients’ quality of life but also lower their survival rate. Although cigarette smoking is traditionally known as the predominant cause of COPD, there have been increasing cases of non-smokers being diagnosed with the disease. COPD is more prevalent among the older population, with the rising prevalence and mortality among women than male, attributed from increased population of female smokers. Other risk factors include occupational exposure to chemical fumes, air pollution, childhood infection, and genetic heredity. Spirometry is regarded as the gold standard diagnostic tool for COPD which can detect COPD at early, asymptomatic stages. There is no cure for COPD, however, there are availability of therapies that can improve symptoms and a patients’ quality of life. Despite the treatment advances, there is still an unmet need for improved pharmacological intervention against COPD, particularly in the reduction of exacerbations and modifying the disease progression. Astegolimab is a drug that is under development for the treatment of patients with COPD. This study will focus on finding out if astegolimab is safe and if it works in comparison to placebo as a treatment for COPD patients who are current or former smokers with a history of frequent exacerbations. If found to be efficacious, participants will be given access to the study drug in an Open Label Extension study (GB43374) subject to approval by relevant health authorities.
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| Abstract of Study: |
STUDY RATIONALE
The purpose of this study is to assess the efficacy and safety of astegolimab compared with placebo in participants with chronic obstructive pulmonary disease (COPD) who are former or current smokers and have a history of frequent exacerbations.
OBJECTIVES AND ENDPOINTS
Primary and selected secondary objectives for the study are expressed using the estimand framework in accordance with the International Conference on harmonization E9 (R1) statistical principles for clinical trials (FDA 2020) in Section 3. The objectives include (but are not limited to) the evaluation of the efficacy and safety of astegolimab compared with placebo.
OVERALL DESIGN
This is a Phase III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of astegolimab in combination with standard of care (SOC) compared with placebo in combination with SOC, in participants with COPD who are former or current smokers and have a history of frequent exacerbations. Approximately 1290 participants with COPD are expected to be enrolled globally.
Following a screening period of at least 7 days and to up to 4 weeks, participants will be randomized in a 1:1:1 ratio to 1 of 3 treatment arms to receive blinded treatment with either astegolimab or placebo. Randomization will be stratified by smoking status at screening (former smoker vs. current smoker) and region.
The first dose of study drug (astegolimab or placebo) will be administered on Day 1; treatment will continue through Week 50, followed by a 12-week safety follow-up period. The treatment regimens for each arm are as follows:
To ensure that all study participants undergo the same visit schedule, participants randomized to the Q4W dosing arm will alternate between injections of astegolimab and placebo Q2W (beginning with astegolimab on Day 1), thus receiving astegolimab Q4W.
Participants will return to the clinic Q2W through the treatment completion visit at Week 52. The primary endpoint analyses will be conducted using the 52-week treatment period data for all participants.
Several key aspects of the study design and study population are summarized below.
STUDY TREATMENT
Astegolimab and placebo will be supplied by the Sponsor as a sterile liquid in 2.25 mL pre-filled syringes with a needle safety device, providing 238 mg/1.7 mL of astegolimab or placebo.
Study drug administration must occur after all other procedures have been completed at the visit, unless specifically indicated otherwise. Study drug will be administered by trained medical personnel.
Each dose of study drug (astegolimab or placebo) will be administered as 2 SC injections (for a total of 3.4 mL), with each injection administered on a different side of the abdomen (i.e., right or left). All participants will be observed for at least 30 minutes after each dose and longer (approximately 60 minutes) in the event of an injection-site reaction, as determined by the investigator. If a participant develops any signs or symptoms to suggest a systemic hypersensitivity reaction or anaphylactic event, longer observation may be warranted as per the opinion of the investigator.
There must be a minimum of 8 days between doses. In the event a dosing visit would occur within 8 days of a subsequent or previous dosing visit (e.g., due to an out-of-window visit), the study drug may not be administered. Instead, the next dose of study drug should be administered at the subsequent scheduled visit within the protocol-defined visit window to ensure that the 8-day minimum dosing interval is maintained.
DURATION OF PARTICIPATION
The total duration of study participation for each individual is expected to be approximately 15 months.
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Q2W = every 2 weeks; Q4W = every 4 weeks; SOC = Standard of Care; SC = Subcutaneous
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