BV2013/5

OM Pharma SA

22 rue du Bois-du-Lan, Geneva, Switzerland, CH-1217 Meyrin 2

Clinical Research Department, OM Pharma SA, +41 79 171 81 38, lorenz.lehr@viforpharma.com

Clinical Research Department, OM Pharma SA, +41 22 783 14 59, lorenz.lehr@viforpharma.com

No

No

No

Final

16 Jun 2016

Yes

31 Jul 2015

Yes

31 Jul 2015

No

To investigate the effect of Broncho-Vaxom® (BV) on the phagocytic ability of monocyte-derived macrophages (MDMs), as a measure of the innate immune system, in subjects with Chronic Obstructive Pulmonary Disease (COPD)

Prior to initiation of the study, the protocol, the patient information sheet, including the Informed Consent Form (ICF), was reviewed and approved by an Independent Ethics Committees (IEC), operating in accordance with current regulations. Any modifications to the protocol, following initial IEC approval, were submitted to the IEC for review and approval prior to implementation, also implying a new signature of the ICF from patient. The study was conducted in accordance with the principles of the Declaration of Helsinki, including amendments in force up to and including the time the study was conducted. The study was conducted in compliance with the International Conference on Harmonisation (ICH) E6 Guideline for Good Clinical Practice (GCP), Committee for Proprietary Medicinal Products Guideline (CPMP/ICH/135/95), and compliant with the European Union Clinical Trial Directive (Directive 2001/20/EC) and/or the Code of Federal Regulations for informed consent and protection of patient rights (21 CFR, Parts 50 and 56). Before each subject was admitted to the study, a signed and dated informed consent was obtained from the subject (or his/her legally authorised representative) according to the regulatory and legal requirements of the participating country. This consent form was retained by the Investigator as part of the study records. A copy of the document was provided to the subject. No investigations specifically required for the study were conducted until valid consent was obtained. Subjects were informed that their participation in the study was entirely voluntary and would have no effect on clinical care otherwise available and that they could withdraw consent to participate at any time without penalty or loss of further medical treatment. Subjects were told that Competent Authorities and authorised persons could examine their records but that personal information would be treated as strictly confidential and would not be publicly available.

21 Aug 2014

No

No

United Kingdom: 58

58

58

0

0

0

0

0

0

10

46

2

Treatment period

Randomised - controlled

Individual study treatment boxes were identified by randomisation number only. BV capsules and placebo capsules were identical in appearance (form, weight, colour, texture of content, etc.) to ensure subject and Investigator blinding.

Yes

Broncho-Vaxom® 7 mg

OM-85 BV

BV

Capsule

Oral use

Subjects were instructed to take 1 capsule per day for 30 consecutive days during the treatment phase of the study. No treatment was administered during the second phase of the study (i.e., 30-day off-treatment period). The medication was to be taken in the morning on an empty stomach with some fluid.

Placebo

Capsule

Oral use

Subjects were instructed to take 1 capsule per day for 30 consecutive days during the treatment phase of the study. No treatment was administered during the second phase of the study (i.e., 30-day off-treatment period). The medication was to be taken in the morning on an empty stomach with some fluid.

Off-treatment follow-up period

Not applicable

Yes

No investigational medicinal product assigned in this arm

No investigational medicinal product assigned in this arm

Broncho-Vaxom® (BV)

Placebo

Safety Set (SS)

All randomised subjects who received at least 1 dose of study medication.

Full Analysis Set (FAS)

All randomised subjects who received at least 1 dose of study drug and had at least 1 baseline and 1 post-baseline assessment of the primary efficacy parameter.

Per Protocol Set (PPS)

All subjects in the Full Analysis Set (FAS) who had no major protocol deviations.

Broncho-Vaxom® (BV)

Placebo

Broncho-Vaxom® (BV)

Placebo

Safety Set (SS)

All randomised subjects who received at least 1 dose of study medication.

Full Analysis Set (FAS)

All randomised subjects who received at least 1 dose of study drug and had at least 1 baseline and 1 post-baseline assessment of the primary efficacy parameter.

Per Protocol Set (PPS)

All subjects in the Full Analysis Set (FAS) who had no major protocol deviations.

Change in phagocytic ability of Monocyte derived macrophages (MDMs) from Baseline (Visit 1, Day -1) to Day 30 (Visit 3), using LOCF (i.e., Day 30 Endpoint), as measured by change in concentration of phagocytosed bacteria following challenge with fluorescently labelled dead bacteria. The change is represented by the standard error of the least squares mean in a mixed analysis model (see subset analysis set). The MDM phagocytosis assay (with H influenzae) was performed on MDMs derived from blood samples collected at Baseline, Day 10, Day 30, and Day 60 (or early termination). The assays were performed at the central laboratory.

Primary

From Baseline to Day 30 Endpoint. For the primary analysis, last observation carried forward (LOCF) imputation was used for missing values at Day 30 (i.e., defined as Day 30 Endpoint).

Change in phagocytic ability of MDMs from Baseline to Day 30 Endpoint (end of treatment), comparing both treatments. Phagocytic ability was measured as the change in concentration of phagocytosed bacteria. The effect of BV treatment (relative to placebo) was tested on the FAS using a mixed model with treatment, baseline bacteria concentration, gender, and COPD disease stage (IV versus I to III) as fixed effects.

Broncho-Vaxom® (BV) v Placebo

54

Pre-specified

169.771

2-sided

Standard error of the mean

228.3938

Change in phagocytic ability of Monocyte derived macrophages (MDMs) from Baseline (Visit 1, Day -1) to Day 30 (Visit 3), using LOCF (i.e., Day 30 Endpoint), as measured by change in concentration of phagocytosed bacteria following challenge with fluorescently labelled dead bacteria. The change is represented by the standard error of the least squares mean in a mixed analysis model (see subset analysis set). The MDM phagocytosis assay (with S pneumoniae) was performed on MDMs derived from blood samples collected at Baseline, Day 10, Day 30, and Day 60 (or early termination). The assays were performed at the central laboratory.

Primary

From Baseline to Day 30 Endpoint. For the primary analysis, last observation carried forward (LOCF) imputation was used for missing values at Day 30 (i.e., defined as Day 30 Endpoint).

Change in phagocytic ability of MDMs from Baseline to Day 30 Endpoint (end of treatment), comparing both treatments. Phagocytic ability was measured as the change in concentration of phagocytosed bacteria. The effect of BV treatment (relative to placebo) was tested on the FAS using a mixed model with treatment, baseline bacteria concentration, gender, and COPD disease stage (IV versus I to III) as fixed effects.

Broncho-Vaxom® (BV) v Placebo

54

Pre-specified

15.363

2-sided

Standard error of the mean

221.632

Adverse events were recorded from the signature of the ICF and until the last study visit (Visit 4/early termination, Day 60).Adverse events persisting at study completion were followed until resolution/stabilisation/lost to follow-up/stop of contact.

17.1

Placebo

Broncho-Vaxom