Safety and Efficacy of QAW039 in Sputum Eosinophilia and Persistent Asthma

NCT01545726 | Completed Phase 2

• 2 other identifiers: CQAW039A22082011-004966-13
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the safety and efficacy of QAW039 when added to current therapy in patients that have sputum eosinophilia and persistent asthma.

Conditions

Asthma

Keywords

Asthma; Sputum eosinophilia; CRTH2 receptor; PGD2 antagonist

Outcome Measures

Primary Outcomes (1)

• Change from baseline in sputum eosinophil percentage at week 12 (baseline measurement is defined as sputum eosinophil percentage at Day1 prior to the first dosing).

  Sputum induction is performed through the inhalation of hypertonic saline. Sputum is collected and assessed for differential cellular content (absolute numbers and percentages). The primary variable will be summarized by treatment and analyzed using an ANCOVA model with treatment as the fixed effect and the respective baseline value as the covariate.

  Visit 3 (day 1); Visit 5 (day 84)

Secondary Outcomes (2)

• Change from baseline to week 12 in Asthma Control Questionnaire (ACQ)

  Visit 3 (day 1); Visit 5 (day 84)

• Safety and tolerability of QAW039 in patients with moderate to severe asthma

  Visit 2 (day -14); Visit 3 (day 1); Visit 4 (day 42); Visit 5 (day 84); Visit 6 (day 126)

Study Arms (2)

QAW039

EXPERIMENTAL

Eligible patients will receive QAW039 po 450 mg daily dose.

Drug: QAW039

Placebo

PLACEBO COMPARATOR

Placebo to QAW039 (oral capsules) will be administered to match QAW039 schedule.

Drug: Placebo

Interventions

QAW039 DRUG

QAW039 was supplied as capsules for oral administration.

QAW039

Placebo DRUG

Placebo was supplied as capsules for oral administration.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained before any assessment is performed.
• Physician diagnosis of asthma, as per GINA guidelines GINA guidelines and currently prescribed ICS or ICS-LABA therapy.
• Patients who are demonstrated to have reversible airway obstruction, significant FEV1 variability or airway hyperresponsiveness (AHR), or who have shown such responses in previous test(s) within the last five years.
• An ACQ score ≥ 1.5 at randomization or ≥ 1 exacerbations (requiring higher than the patient's normal dose of OCS or IV corticosteroids for ≥ 3 days) in the past 12 months. The definition of exacerbations includes episodes during which the patient self-administered higher doses of OCS as part of a documented self-management plan initiated by the patient's general practitioner or respiratory physician.
• Patients currently on GINA step 2 to step 5 asthma therapies.
• Sputum eosinophil count ≥ 2% at screening.

You may not qualify if:

• Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes (CRTH2 antagonists).
• History of long QT syndrome or whose QTc interval (Fridericia's) is prolonged \>450 msec for males and \>470 msec for females at screening or baseline.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/mL).
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during the study treatment and for 5 days (5 half-lives) after treatment.
• Acute illness other than asthma which, in the investigator's opinion, may compromise the well-being of the patient or study endpoint assessments at the start of the study
• Recent (within 6 weeks of screening) or current lower respiratory tract infection.
• Patients who have been hospitalized or required high-dose (\>10mg prednisolone/day) oral corticosteroid (OCS) therapy within 6 weeks of the screening visit.
• Patients with clinically significant laboratory abnormalities (not associated with the study indication) at screening.
• Patients who have a clinically significant abnormality on a 12-lead ECG recorded within one month prior to or at screening.
• Patients with a body mass index (BMI) \< 17 or \> 40 kg/m2.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Leicester, LE3 9QP, United Kingdom

Location

Related Publications (1)

• Gonem S, Berair R, Singapuri A, Hartley R, Laurencin MFM, Bacher G, Holzhauer B, Bourne M, Mistry V, Pavord ID, Mansur AH, Wardlaw AJ, Siddiqui SH, Kay RA, Brightling CE. Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial. Lancet Respir Med. 2016 Sep;4(9):699-707. doi: 10.1016/S2213-2600(16)30179-5. Epub 2016 Aug 5.

  PMID: 27503237 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

fevipiprant

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2012
• First Posted: March 7, 2012
• Study Start: February 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: October 9, 2013

Record last verified: 2013-10

Locations

GB (1)