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

Novartis

Status and phase: Completed; Phase 3

Conditions: Asthma

Treatments: Drug: QAW039; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02555683

CQAW039A2307

2015-002553-35 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 894 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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894 participants in 3 patient groups, including a placebo group

QAW039 150 mg

Experimental group

Description:

QAW039 150 mg once daily

Treatment:

Drug: QAW039

Drug: QAW039

QAW039 450 mg

Experimental group

Description:

QAW039 450 mg once daily

Treatment:

Drug: QAW039

Drug: QAW039

Placebo

Placebo Comparator group

Description:

Placebo once daily

Treatment:

Drug: Placebo