Study of Efficacy and Safety of QAW039 in Patients With Severe Asthma Inadequately Controlled With Standard of Care Asthma Treatment.

NCT ID: NCT02555683

Last Updated: 2020-05-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 894 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-11
• Study Completion Date: 2019-11-04

Brief Summary

This study aimed to determine the efficacy and safety of QAW039 150 mg and QAW039 450 mg, compared with placebo, when added to GINA (Global Initiative for Asthma) steps 4 and 5 standard-of- care (SoC) asthma therapy (GINA 2016) in the following two populations:

• patient with inadequately controlled severe asthma and high eosinophil counts at baseline (eosinophil count at Visit 1 ≥250 cells/ µl) (sub-population)
• patients with inadequately controlled severe asthma (overall study population)

Inadequate control is defined as partly controlled or uncontrolled asthma (GINA 2016).

Detailed Description

This study used a randomized, multicenter, double-blind, placebo-controlled parallel-group design in which QAW039 150 mg or QA039 450 mg or placebo was added to standard of care, GINA steps 4 and 5 asthma therapy.

The study included:

• Screening period of up to 2 weeks to assess eligibility;
• Run-in period of approximately 2 weeks and a maximum of 6 weeks on placebo to collect baseline data for efficacy variables and compliance with the Electronic Peak Flow/ eDiary device. Upon completion of the run-in period, all patients who met the eligibility criteria were randomized to one of three treatments: QAW039 150 mg or QAW039 450 mg or placebo once daily in a ratio of 1:1:1.
• Treatment period of 52 weeks (assessment period for all Primary and Secondary Outcome Measures). Clinic visits were scheduled approximately 4 weeks after randomization and then at approximately 8-week intervals during the active-treatment period. Phone calls occurred at specified time points between visits occurring at 8-week intervals. Patients who had successfully completed 52 weeks of treatment in this study were offered an optional participation in a safety study (CQAW039A2315).
• Follow-up period of 4 weeks, investigational and drug-free, following the last dose of study drug. A follow-up visit occurred approximately 4 weeks (i.e., approximately 30 days) following the last dose of study therapy to complete safety assessments and pregnancy testing (if applicable). the follow-up period applied to all patients except those patients who had entered the safety study (CQAW039A2315) directly after the Week 52 study visit.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

QAW039 150 mg

QAW039 150 mg once daily

Group Type: EXPERIMENTAL

QAW039

Intervention Type: DRUG

QAW039 150 mg once daily

QAW039 450 mg

QAW039 450 mg once daily

Group Type: EXPERIMENTAL

QAW039

Intervention Type: DRUG

QAW039 450 mg once daily

Placebo

Placebo once daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo once daily

Interventions

QAW039

QAW039 150 mg once daily

Intervention Type: DRUG

QAW039

QAW039 450 mg once daily

Intervention Type: DRUG

Placebo

Placebo once daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Written informed consent and assent (if applicable).
• Male and female patients aged ≥12 years (or ≥lower age limit allowed by health authority and/or ethics committee/institutional review board approvals).
• A diagnosis of severe asthma, uncontrolled on GINA 4/5 asthma medication.
• Evidence of airway reversibility or airway hyper- reactivity.
• FEV1 of ≤80% of the predicted normal value for patients aged ≥18 years; FEV1 of ≤90% for patients aged 12 to <18 years
• An ACQ score ≥1.5.
• A history of 2 or more asthma exacerbations within the 12 months prior to entering the study.

Exclusion Criteria

• Use of other investigational drugs within 5 half-lives of study entry, or within 30 days, whichever is longer.
• Subjects who have participated in another trial of QAW039.
• A QTcF (Fridericia) ≥450 msec (male) or ≥460 msec (female).
• History of malignancy with the exception of local basal cell carcinoma of the skin.
• Pregnant or nursing (lactating) women.
• Serious co-morbidities.
• Patients on greater than 20 mg of simvastatin, greater than 40 mg of atorvastatin, greater than 40 mg of pravastatin, or greater than 2 mg of pitavastatin

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis

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United States; Argentina; Australia; Austria; Belgium; Brazil; China; Denmark; Estonia; Finland; France; Germany; Greece; Guatemala; Hungary; Iceland; Ireland; Latvia; Lithuania; Philippines; Poland; Romania; Singapore; Spain; Switzerland; United Kingdom; Vietnam

References

Brightling CE, Gaga M, Inoue H, Li J, Maspero J, Wenzel S, Maitra S, Lawrence D, Brockhaus F, Lehmann T, Brindicci C, Knorr B, Bleecker ER. Effectiveness of fevipiprant in reducing exacerbations in patients with severe asthma (LUSTER-1 and LUSTER-2): two phase 3 randomised controlled trials. Lancet Respir Med. 2021 Jan;9(1):43-56. doi: 10.1016/S2213-2600(20)30412-4. Epub 2020 Sep 24.

Reference Type: DERIVED

PMID: 32979986 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

2015-002553-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CQAW039A2307

Identifier Type: -

Identifier Source: org_study_id