Clinical trial NCT01545726: Safety and Efficacy of QAW039 in Sputum Eosinophilia and Persistent Asthma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
Sputum eosinophilia
CRTH2 receptor
PGD2 antagonist
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-03-07
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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).
timeFrame: Visit 3 (day 1); Visit 5 (day 84)
Secondary outcomes:
measure: Change from baseline to week 12 in Asthma Control Questionnaire (ACQ)
timeFrame: Visit 3 (day 1); Visit 5 (day 84)
measure: Safety and tolerability of QAW039 in patients with moderate to severe asthma
timeFrame: Visit 2 (day -14); Visit 3 (day 1); Visit 4 (day 42); Visit 5 (day 84); Visit 6 (day 126)
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.