Dose-range Finding Efficacy and Safety Study for QBW251 in COPD Patients

Novartis

Status and phase: Completed; Phase 2

Conditions: Pulmonary Disease, Chronic Obstructive

Treatments: Drug: COPD maintenance background therapy; Drug: QBW251; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04072887

CQBW251B2201

2018-003197-28 (EudraCT Number)

Details and patient eligibility

About

This clinical study was designed to support the dose selection for future studies by evaluating efficacy and safety of different QBW251 doses in Chronic obstructive pulmonary disease (COPD) patients with chronic bronchitis and a history of exacerbations, compared to placebo, when added to a triple inhaled therapy of LABA, LAMA and ICS.

Full description

This study used a 6 treatment arm, parallel-group, randomized, double-blind study design. 974 male and female COPD patients were randomized into the trial. The study consisted of four distinct study periods:

• Screening (Weeks -3 to -2): Participants underwent a screening period of 1 week where were assessed for eligibility and tapered off disallowed medications.
• Run-in (Days -14 to 1): Subsequently, participants entered the run-in period of up to 2 weeks to establish baseline values for symptom assessments, to standardize the COPD background therapy (triple combination LABA/LAMA/ICS), and to complete eligibility assessments.
• Treatment (Day 1 to Week 24): Eligible participants moved into the Day 1 visit where they were stratified according to their smoking status (current or ex-smoker) and severity of airflow limitation (FEV1 ≥ 30% to < 50% and ≥ 50% to < 80%) and then randomized into 1 of 6 treatment arms with a randomization ratio of 2:2:1:1:1:2 (450 mg b.i.d., 300 mg b.i.d., 150 mg b.i.d., 75 mg b.i.d., 25 mg b.i.d., placebo). The treatment period consisted of 24 weeks, during which the participant returned to the site for regular visits (Day 1 - Week 24). QBW251 450 mg arm was discontinued early based on a pre-defined pharmacokinetic exposure stopping rule.
• Follow-up (Weeks 25-28): Upon completion of the treatment period, participants were followed up for safety assessments for 30 days.

Enrollment: 974 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male and female COPD patients aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure.
• Current or ex-smokers who have a smoking history of at least 10 pack years.
• Patients who have been treated with a triple combination of LABA/LAMA/ICS for the last 3 months prior to screening.
• Patients featuring chronic bronchitis

Exclusion criteria

• Patients who have had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization, or a respiratory tract infection in the 4 weeks prior to screening, or between screening and randomization.
• Patients with any documented history of asthma, or with an onset of chronic respiratory symptoms, including a COPD diagnosis, prior to age 40 years.
• Patients with a body mass index (BMI) of more than 40 kg/m2.
• Use of other investigational drugs (approved or unapproved) within 30 days or 5 half-lives prior to screening, or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations.
• Pregnant or nursing (lactating) women, and women of childbearing potential not willing to use acceptable effective methods of contraception during study participation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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974 participants in 6 patient groups, including a placebo group

QBW251 450 mg

Experimental group

Description:

QBW251 was orally administered 450 mg b.i.d for 24 weeks

Treatment:

Drug: COPD maintenance background therapy

Drug: QBW251

QBW251 300 mg

Experimental group

Description:

QBW251 was orally administered 300 mg b.i.d for 24 weeks

Treatment:

Drug: COPD maintenance background therapy

Drug: QBW251

QBW251 150 mg

Experimental group

Description:

QBW251 was orally administered 150 mg b.i.d for 24 weeks

Treatment:

Drug: COPD maintenance background therapy

Drug: QBW251

QBW251 75 mg

Experimental group

Description:

QBW251 was orally administered 75 mg b.i.d for 24 weeks

Treatment:

Drug: COPD maintenance background therapy

Drug: QBW251

QBW251 25 mg

Experimental group

Description:

QBW251 was orally administered 25 mg b.i.d for 24 weeks

Treatment:

Drug: COPD maintenance background therapy

Drug: QBW251

Placebo

Placebo Comparator group

Description:

Placebo was orally administered b.i.d for 24 weeks

Treatment:

Drug: COPD maintenance background therapy

Drug: Placebo