OC000459/019/15

Atopix Therapeutics Ltd

Innovation Centre, 99 Park Drive, Milton Park, Abingdon, United Kingdom, OX14 4RY

Clinical Trial Transparency, Chiesi Farmaceutici S.p.A., clinicaltrials_info@chiesi.com

Clinical Trial Transparency, Chiesi Farmaceutici S.p.A., clinicaltrials_info@chiesi.com

No

No

No

Final

25 Feb 2019

No

Yes

02 Aug 2018

No

To determine the effect of OC000459 on induced sputum eosinophil counts at 12 weeks of treatment compared to placebo.

The protocol, together with all required clinical trial documentation, was submitted to the appropriate independent ethics committee (IEC) in all participating sites. A copy of the favourable opinion from the IEC had to be received before the trial could be initiated at an investigational site.This study was conducted in accordance with ICH Good Clinical Practice (GCP) Guideline E6 (1996), the Declaration of Helsinki and the UK Statutory Instrument which incorporates the European Clinical Trial Directives (Directives 2001/20/EC and 2005/28/EC) and subsequent amendments. This study was also performed in compliance with the requirements of the Medicines and Healthcare products Regulatory Agency (MHRA). The consent document met all applicable local laws and provided the patient with information regarding the purpose, procedures, requirements and restrictions of the study, along with any known risks and potential benefits associated with the investigational product and the established provisions for maintaining the confidentiality of personal information. Subject’s written informed consent obtained prior to any study-related procedures.

09 Sep 2016

No

No

United Kingdom: 40

40

40

0

0

0

0

0

0

25

14

1

Treatment period (overall period)

Randomised - controlled

Randomisation was performed according to the method of minimisation by a designated unblinded statistician. The allocation ratio to OC000459 and placebo was 1:1. Further details of the implementation of the minimisation process were contained in the Randomisation and Blinding Plan. Randomisation code information was sent securely by an unblinded statistician for packaging study drug. Copies of the randomisation codes were stored securely by the unblinded statistician.

Yes

OC000459

OC000459

CP003

Tablet

Oral use

50mg of OC000459 (1 tablet) once daily. Subjects who were not treated with OCS at Baseline received 12 weeks treatment with OC000459. Subjects who were receiving OCS at Baseline received OC000459 for 24 weeks; the second 12 weeks of the study were performed in order to evaluate the effects of OCS dose reduction on symptoms and measures of disease activity.

Placebo for OC000459

CP004

Tablet

Oral use

1 tablet of placebo once daily. Subjects who were not treated with OCS at Baseline received 12 weeks treatment with placebo. Subjects who were receiving OCS at Baseline received placebo for 24 weeks; the second 12 weeks of the study were performed in order to evaluate the effects of OCS dose reduction on symptoms and measures of disease activity.

Study Treatment

Placebo

Study Treatment - FAS

The full analysis set (FAS) consisted of all randomised subjects who received at least one dose of double-blind study medication, and had at least one post-baseline primary efficacy assessment , irrespective of compliance with other eligibility and protocol criteria. For each efficacy endpoint, the analysis was based on the FAS.

Study Treatment - Safety

The safety analysis set consisted of all subjects who received at least one dose of double-blind study medication irrespective of compliance with eligibility and other protocol criteria. All safety analyses were performed on the safety analysis set.

Placebo - FAS

The full analysis set (FAS) consisted of all randomised subjects who received at least one dose of double-blind study medication, and had at least one post-baseline primary efficacy assessment , irrespective of compliance with other eligibility and protocol criteria. For each efficacy endpoint, the analysis was based on the FAS.

Placebo - Safety

The safety analysis set consisted of all subjects who received at least one dose of double-blind study medication irrespective of compliance with eligibility and other protocol criteria. All safety analyses were performed on the safety analysis set.

Study Treatment

Placebo

Study Treatment - FAS

The full analysis set (FAS) consisted of all randomised subjects who received at least one dose of double-blind study medication, and had at least one post-baseline primary efficacy assessment , irrespective of compliance with other eligibility and protocol criteria. For each efficacy endpoint, the analysis was based on the FAS.

Study Treatment - Safety

The safety analysis set consisted of all subjects who received at least one dose of double-blind study medication irrespective of compliance with eligibility and other protocol criteria. All safety analyses were performed on the safety analysis set.

Placebo - FAS

The full analysis set (FAS) consisted of all randomised subjects who received at least one dose of double-blind study medication, and had at least one post-baseline primary efficacy assessment , irrespective of compliance with other eligibility and protocol criteria. For each efficacy endpoint, the analysis was based on the FAS.

Placebo - Safety

The safety analysis set consisted of all subjects who received at least one dose of double-blind study medication irrespective of compliance with eligibility and other protocol criteria. All safety analyses were performed on the safety analysis set.

Sputum was induced using nebulised hypertonic saline and processed using standard methods. Sputum was induced using 3%, 4% and 5% saline inhaled in sequence for five minutes via an ultrasonic nebuliser. After each inhalation subjects blew their nose and rinsed their mouth to minimise nasal contamination and expectorated sputum into a sterile pot. Change from baseline at Week 12 of the logarithmic value (log10) of induced sputum eosinophil count data (%) was analysed. Data are presented as adjusted geometric mean ratios with their 95% confidence intervals (CIs).

Primary

from baseline to week 12

The ratio of induced sputum eosinophil count (%) at Week 12 to baseline was estimated from the analysis of change from baseline at Week 12 of the logarithmic value (log10) of induced sputum eosinophil count data (%). Data are presented as adjusted geometric mean ratio with its 95% CI. Analysis is based on an analysis of covariance model including treatment and use of OCS at screening (yes/no) as factors and baseline induced sputum eosinophils (log10 value) as covariate.

Study Treatment - FAS v Placebo - FAS

39

Pre-specified

0.431

2-sided

Spirometry was measured at all visits with a validated and standardised spirometer with the FEV1 and FVC recorded as the best of 3 successive readings within 100 ml. Spirometry was performed before and 20 minutes after the subject received nebulised salbutamol 2.5 mg. Results of change from baseline in FEV1 BEFORE salbutamol only are reported.

Secondary

From baseline to week 12.

Data are presented as adjusted mean treatment difference (OC000459 vs Placebo) of change from baseline at Week 12 with 95% CI. Analysis is based on an analysis of covariance model including treatment, use of OCS at Screening (yes/no) and screening sputum eosinophil percentage category (>3% and ≤10%,>10% and ≤35%,>35%) as factors, and baseline FEV1 as a covariate.

Study Treatment - FAS v Placebo - FAS

39

Pre-specified

0.127

2-sided

Spirometry was measured at all visits with a validated and standardised spirometer with the FEV1 and FVC recorded as the best of 3 successive readings within 100 ml. Spirometry was performed before and 20 minutes after the subject received nebulised salbutamol 2.5 mg. Results of change from baseline in FVC BEFORE salbutamol only are reported.

Secondary

From baseline to week 12

The ACQ-5 five-item questionnaire, developed as a measure of subject’ asthma control ,was completed at every scheduled visit after Screening. The questions are designed to be self-completed by the subject. The five questions enquire about the frequency and/or severity of symptoms (waking at night, severity of asthma symptoms, activity limitation, shortness of breath and wheeze). The response options for all these questions consist of a zero (no impairment/limitation) to six (total impairment/limitation) scale.

Secondary

from baseline to week 12

Data are presented as adjusted mean treatment difference (OC000459 vs Placebo) of change from baseline at Week 12 with 95% CI. Analysis is based on an analysis of covariance model including treatment, use of OCS at Screening (yes/no) and screening sputum eosinophil percentage category (>3% and ≤10%,>10% and ≤35%,>35%) as factors, and baseline ACQ-5 average score as a covariate.

Study Treatment - FAS v Placebo - FAS

39

Pre-specified

0.043

2-sided

The ACQ-5 five-item questionnaire, developed as a measure of subject’ asthma control ,was completed at every scheduled visit after Screening. The questions are designed to be self-completed by the subject. The five questions enquire about the frequency and/or severity of symptoms (waking at night, severity of asthma symptoms, activity limitation, shortness of breath and wheeze). The response options for all these questions consist of a zero (no impairment/limitation) to six (total impairment/limitation) scale. ACQ-5 response is defined as a change from baseline in ACQ-5 Average Score ≤-0.5. If the change from baseline was > -0.5, the subject was classified as a non-responder in terms of ACQ-5. Subjects with missing ACQ-5 average score value at Week 12 were also classified as non-responders.

Secondary

from baseline to week 12

Analysis is based on a logistic regression model including treatment, use of OCS at Screening (yes/no) and screening sputum eosinophil percentage category (>3% and ≤10%,>10% and ≤35%,>35%) as factors, and baseline ACQ-5 average score as a covariate. The odds ratio for the treatment with its 95% CI and corresponding p-value were estimated by the model.

Study Treatment - FAS v Placebo - FAS

39

Pre-specified

0.33

2-sided

The AQLQ(S) is a standardised version of the Asthma Quality of Life Questionnaire and was given to subjects to complete at every scheduled visit after Screening. Subjects were asked to think about how they had been during the previous two weeks and to respond to each of the 32 questions on a 7-point scale (7 = not impaired at all to 1 = severely impaired). The overall AQLQ(S) score is the mean of all 32 responses and the individual domain scores are the means of the items in those domains (adjusted means with a 95% CI).

Secondary

from baseline to week 12

Data are presented as adjusted mean treatment difference (OC000459 vs Placebo) of change from baseline at Week 12 with 95% CI. Analysis is based on an analysis of covariance model including treatment, use of OCS at Screening (yes/no) and screening sputum eosinophil percentage category (>3% and ≤10%,>10% and ≤35%,>35%) as factors, and baseline AQLQ average score as a covariate.

Study Treatment - FAS v Placebo - FAS

39

Pre-specified

-0.027

2-sided

The AQLQ(S) is a standardised version of the Asthma Quality of Life Questionnaire and was given to subjects to complete at every scheduled visit after Screening. Subjects were asked to think about how they had been during the previous two weeks and to respond to each of the 32 questions on a 7-point scale (7 = not impaired at all to 1 = severely impaired). The overall AQLQ(S) score is the mean of all 32 responses and the individual domain scores are the means of the items in those domains. AQLQ response is defined as a change from baseline in AQLQ Average Score ≥ 0.5. If the change from baseline was < 0.5, the subject was classified as a non-responder in terms of AQLQ. Subjects with missing AQLQ average score value at Week 12 were also classified as non-responders.

Secondary

from baseline to week 12

Analysis is based on a logistic regression model including treatment, use of OCS at Screening (yes/no) and screening sputum eosinophil percentage category (>3% and ≤10%,>10% and ≤35%,>35%) as factors, and baseline AQLQ average score as a covariate. The odds ratio for the treatment with its 95% CI and corresponding p-value were estimated by the model.

Study Treatment - FAS v Placebo - FAS

39

Pre-specified

1.45

2-sided

AE, SAE,ADR were collected in first 12 weeks (form Week 0 to week 12)

Adverse events were reported for the Safety Population

20.0

Study Treatment - Safety

Placebo - Safety