CQAW039A2323

Novartis Pharma AG

CH-4002, Basel, Switzerland,

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com

No

No

No

Final

06 Feb 2020

No

Yes

06 Feb 2020

Yes

The main purpose of this study was to determine the efficacy of fevipiprant (150 mg and 450 mg once daily), compared with placebo, as add-on to GINA (Global Initiative for Asthma) treatment step 4 or 5 standard-of-care (SoC) asthma therapy in terms of avoidance of systemic corticosteroids (SCS) use over 52 weeks in patients with inadequately controlled severe asthma and high eosinophil counts (eosinophil count at Visit 1 ≥250 cells/ μl) and in the overall patient population regardless of eosinophil counts.

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial. Patients were provided SABA (primary rescue medication such as salbutamol 100 mcg or albuterol 90 mcg) as rescue medication to be used on an ‘as needed basis’ during the study. Nebulized formulation of salbutamol/albuterol was not permitted. Oral corticosteroids (add on rescue medication such as prednisone/prednisolone (or equivalent) tablets) were permitted, as instructed by the treating physician, as part of a written asthma plan for the treatment of acute asthma exacerbations and/or symptoms.

13 Dec 2018

No

No

Argentina: 153

Chile: 6

Colombia: 6

Peru: 17

Philippines: 22

Russian Federation: 54

South Africa: 15

Thailand: 3

Turkey: 9

United States: 36

Vietnam: 14

Belgium: 8

Bulgaria: 13

Czechia: 31

France: 5

Germany: 106

Greece: 10

Hungary: 63

Slovakia: 17

Spain: 9

United Kingdom: 7

604

262

0

0

0

0

0

0

498

106

0

Overall Study (overall period)

Randomised - controlled

Yes

fevipiprant

QAW039

Tablet

Oral use

QAW039 150 mg once daily orally

fevipiprant

QAW039

Tablet

Oral use

QAW039 450 mg once daily orally

placebo

Tablet

Oral use

Placebo to QAW039 once daily orally

QAW039 150 mg

QAW039 450 mg

Placebo

QAW039 150 mg

QAW039 450 mg

Placebo

All participants were provided with prednisone/prednisolone (or equivalent) tablets that could be used according to the asthma plan along with an electronic diary (e-Diary/ePEF). Daily use of oral corticosteroids (number of tablets taken in the previous 12 hours) was recorded once in the morning and once in the evening by the subject in the eDiary/PEF device. In case of use of injectable corticosteroids during certain circumstances (eg. hospitalization) the data was collected on the eCRF (electronic case report form). The total systemic corticosteroids (SCS) dose data was aggregated into monthly data for analysis. For the patients discontinuing treatment early, the total SCS dose for 52 weeks was obtained as annualized SCS dose. For example if patient took 120 mg for 3 months then for 12 months patient will be taking 120*12/3=480mg total SCS dose. The mean values over 52 weeks in the overall patient population regardless of peripheral blood eosinophil counts are reported here.

Primary

52 weeks

QAW039 150 mg v Placebo

402

Pre-specified

QAW039 450 mg v Placebo

401

Pre-specified

All participants were provided with prednisone/prednisolone (or equivalent) tablets that could be used according to the asthma plan along with an electronic diary (e-Diary/ePEF). Daily use of oral corticosteroids (number of tablets taken in the previous 12 hours) was recorded once in the morning and once in the evening by the subject in the eDiary/PEF device. In case of use of injectable corticosteroids during certain circumstances (eg. hospitalization) the data was collected on the eCRF (electronic case report form). The total systemic corticosteroids (SCS) dose data was aggregated into monthly data for analysis. For the patients discontinuing treatment early, the total SCS dose for 52 weeks was obtained as annualized SCS dose. For example if patient took 120 mg for 3 months then for 12 months patient will be taking 120*12/3=480mg total SCS dose. The mean values over 52 weeks in the subpopulation of patients with high peripheral blood eosinophil count at baseline are reported here.

Primary

52 weeks

QAW039 150 mg v Placebo

254

Pre-specified

QAW039 450 mg v Placebo

258

Pre-specified

All participants were provided with an electronic diary (eDiary/ePEF) to record asthma symptom twice per day. Daytime asthma symptoms were assessed before bed and nighttime asthma symptoms on awakening. The daytime asthma symptom score included 4 questions with a range of response categories for each question from 0 to 6 (0 = totally controlled; 6 = extremely poorly controlled). The questions were equally weighted and the overall score (from 0 to 6) was calculated as the average of the 4 questions with higher values indicating more asthma symptoms. Mean values of daytime asthma symptom scores were calculated over 4-week intervals during the treatment period. The baseline values of daytime asthma symptoms scores were defined as the average score during the run-in period. A negative change from baseline in daytime asthma symptom score is a favorable outcome.

Secondary

Baseline, up to Week 29-32

All participants were provided with an electronic diary (eDiary/ePEF) to record asthma symptom twice per day. Daytime asthma symptoms were assessed before bed and nighttime asthma symptoms on awakening. The nighttime asthma symptom score included 1 question with a range of response categories from 0 to 3 (0 = no awakening with asthma symptoms; 3 = awake all night). Mean values of nighttime asthma symptom scores were calculated over 4-week intervals during the treatment period. The baseline values of nighttime asthma symptoms scores were defined as the average score during the run-in period. A negative change from baseline in nighttime asthma symptom score is a favorable outcome.

Secondary

Baseline, up to Week 29-32

The Asthma Control Questionnaire (ACQ-5) was completed by the patients at the investigator’s site. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions were equally weighted and the ACQ-5 score was the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled). The baseline values of ACQ-5 score were defined as the ACQ-5 scores obtained on Day 1. A negative change from baseline in ACQ-5 score is a favorable outcome.

Secondary

Baseline, up to Week 28

The Asthma Quality of Life Questionnaire (AQLQ+12) was completed by the patients at the investigator’s site. The AQLQ+12 is a 32-item disease specific questionnaire designed to measure functional impairments that are most important to patients with asthma. Patients were asked to recall their experiences during the previous 2 weeks and to score each of the 32 items on a 7-point scale, where 1 indicates maximal impairment and 7 indicates no impairment. Thus, higher scores indicate better asthma-related quality of life. Each item of the AQLQ+12 was equally weighted and the overall score was the mean score of all 32 items and therefore ranged between 1 and 7. The baseline values of AQLQ+12 score were defined as the AQLQ+12 scores obtained on Day 1. A positive change from baseline in AQLQ+12 score is a favorable outcome.

Secondary

Baseline, up to Week 28

All participants were provided with prednisone/prednisolone (or equivalent) tablets that could be used according to the asthma plan along with an electronic diary (e-Diary/ePEF) to record medication use. Daily use of oral corticosteroids (the number of tablets taken in the previous 12 hours) was recorded once in the morning and once in the evening by the subject using the eDiary/PEF device. In case of use of injectable corticosteroids during certain circumstances (eg. hospitalization) the data was collected on the eCRF (electronic case report form). The percentage of patients requiring ≥ 7.5 mg systemic corticosteroid dose in mg prednisone/prednisolone (or equivalent) per day continuously for at least 30 days within the on-treatment period is presented in this record.

Secondary

Up to 36 weeks

All participants were provided with prednisone/prednisolone (or equivalent) tablets that could be used according to the asthma plan along with an electronic diary (e-Diary/ePEF) to record medication use. Daily use of oral corticosteroids (the number of tablets taken in the previous 12 hours) was recorded once in the morning and once in the evening by the subject using the eDiary/PEF device. In case of use of injectable corticosteroids during certain circumstances (eg. hospitalization) the data was collected on the eCRF (electronic case report form). The percentage of patients with no systemic corticosteroids use up to visit on Week 36 is presented in this record.

Secondary

Week 36

As part of the flexible therapy, investigators were allowed to prescribe biologics approved for asthma from randomization visit onwards. Prescription of biologic therapy during the treatment period was recorded. The proportion of patients with prescription of biologic therapy during the on-treatment period is presented in this record.

Secondary

Up to 36 weeks

Adverse events (AEs) are presented from first dose of study treatment until last dose plus 14 days. Serious AEs are presented from first dose of study treatment until last dose plus 30 days, up to maximum duration of 40 weeks.

Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.

22.1

QAW039 150mg

QAW039 450mg

Placebo