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Safety and Efficacy of QAW039 in Sputum Eosinophilia and Persistent Asthma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01545726
First received: March 1, 2012
Last updated: October 8, 2013
Last verified: October 2013
  Purpose

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


Condition Intervention Phase
Asthma
Drug: QAW039
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Placebo-controlled Study Examining the Effect of Orally Administered QAW039 on Sputum Eosinophil Levels and Other Efficacy Outcomes in Patients With Sputum Eosinophilia and Persistent Asthma

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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). [ Time Frame: Visit 3 (day 1); Visit 5 (day 84) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change from baseline to week 12 in Asthma Control Questionnaire (ACQ) [ Time Frame: Visit 3 (day 1); Visit 5 (day 84) ] [ Designated as safety issue: No ]
    Participants complete the Asthma Control Questionnaire (ACQ). The ACQ has 7 equally weighted items; 5 on symptom assessment, 1 on rescue bronchodilator use and 1 on airway caliber Forced Expiratory Volume in one second (FEV1) % predicted. Items 1-6 are scored along a 7 point response scale, where 0 = good control and 6 = poor control. The 7th item on % predicted FEV1 (pre-bronchodilator) is scored by clinic staff on a 7 point scale. Secondary variables are summarized by treatment and analyzed using ANCOVA model with treatment as the fixed effect and the respective baseline value as covariate.

  • Safety and tolerability of QAW039 in patients with moderate to severe asthma [ Time Frame: Visit 2 (day -14); Visit 3 (day 1); Visit 4 (day 42); Visit 5 (day 84); Visit 6 (day 126) ] [ Designated as safety issue: Yes ]
    All safety endpoints (including adverse events, laboratory data, vital signs and ECG) will be summarized by treatment group for all patients in the safety population. All data will be included in the analysis regardless of rescue medication use.


Enrollment: 61
Study Start Date: February 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: QAW039
Eligible patients will receive QAW039 po 450 mg daily dose.
Drug: QAW039
QAW039 was supplied as capsules for oral administration.
Placebo Comparator: Placebo
Placebo to QAW039 (oral capsules) will be administered to match QAW039 schedule.
Drug: Placebo
Placebo was supplied as capsules for oral administration.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent must be obtained before any assessment is performed.
  2. Physician diagnosis of asthma, as per GINA guidelines GINA guidelines and currently prescribed ICS or ICS-LABA therapy.
  3. 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.
  4. 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.
  5. Patients currently on GINA step 2 to step 5 asthma therapies.
  6. Sputum eosinophil count ≥ 2% at screening.

Exclusion Criteria:

  1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
  2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes (CRTH2 antagonists).
  3. 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.
  4. 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.
  5. 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).
  6. 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.
  7. 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
  8. Patients who are considered unsuitable for inclusion by the assessing physician due to serious co-morbidities such as cancer, emphysema or significant bronchiectasis.
  9. Recent (within 6 weeks of screening) or current lower respiratory tract infection.
  10. Patients who have been hospitalized or required high-dose (>10mg prednisolone/day) oral corticosteroid (OCS) therapy within 6 weeks of the screening visit.
  11. Patients with clinically significant laboratory abnormalities (not associated with the study indication) at screening.
  12. Patients who have a clinically significant abnormality on a 12-lead ECG recorded within one month prior to or at screening.
  13. Patients with a body mass index (BMI) < 17 or > 40 kg/m2.

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01545726

Locations
United Kingdom
Novartis Investigative Site
Leicester, United Kingdom, LE3 9QP
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01545726     History of Changes
Other Study ID Numbers: CQAW039A2208, 2011-004966-13
Study First Received: March 1, 2012
Last Updated: October 8, 2013
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Asthma
Sputum eosinophilia
CRTH2 receptor
PGD2 antagonist

Additional relevant MeSH terms:
Asthma
Eosinophilia
Bronchial Diseases
Hematologic Diseases
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Leukocyte Disorders
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on November 20, 2014