Clinical Trial Results:
A Phase 2, Randomized, Double-blind, Placebo-controlled, Efficacy and Safety Study of Inhaled JNJ-49095397 (RV568) in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease
Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
Summary
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EudraCT number |
2012-005184-27 |
Trial protocol |
BE GB DE HU CZ NL PL RO |
Global end of trial date |
01 Sep 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Apr 2016
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First version publication date |
22 Apr 2016
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
49095397OPD2001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01867762 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Janssen-Cilag International NV
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Sponsor organisation address |
Archimedesweg 29-2333CM, Leiden, Netherlands, 2333CM
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Public contact |
Clinical Registry Group, Janssen-Cilag International NV, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group, Janssen-Cilag International NV, ClinicalTrialsEU@its.jnj.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Sep 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Sep 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of this study was to assess the efficacy (as measured by change from baseline in prebronchodilator [preBD] percent predicted forced expiratory volume in 1 second [FEV1]) of JNJ-49095397 compared with placebo in subjects with symptomatic moderate (global initiative for chronic obstructive lung disease [GOLD] Grade II) to severe (GOLD Grade III) chronic obstructive pulmonary disease (COPD).
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Protection of trial subjects |
The safety assessments included the incidence and severity of adverse events (AEs), clinical laboratory tests (hematology, serum chemistry and urinalysis), electrocardiogram (ECG), vital signs and physical examinations which were assessed throughout the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Aug 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 6
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Country: Number of subjects enrolled |
Canada: 26
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Country: Number of subjects enrolled |
Czech Republic: 18
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Country: Number of subjects enrolled |
Germany: 35
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Country: Number of subjects enrolled |
United Kingdom: 13
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Country: Number of subjects enrolled |
Hungary: 17
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Country: Number of subjects enrolled |
Netherlands: 11
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Country: Number of subjects enrolled |
Poland: 25
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Country: Number of subjects enrolled |
Romania: 9
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Country: Number of subjects enrolled |
Russian Federation: 25
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Country: Number of subjects enrolled |
United States: 26
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Worldwide total number of subjects |
211
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EEA total number of subjects |
134
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
108
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From 65 to 84 years |
103
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 211 subjects were randomized in the study out of these 106 subjects were randomized to the placebo group and 105 subjects were randomized to the JNJ-49095397 400 microgram (µg) group. | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study Period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||
Arm description |
Subjects received Placebo capsule oral inhalation once daily using dry powder inhaler for 12 Weeks. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder, hard capsule
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Routes of administration |
Inhalation use
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Dosage and administration details |
Subjects received Placebo once daily by using a dry powder inhaler for 12 weeks.
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Arm title
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JNJ-49095397 | ||||||||||||||||||||||||
Arm description |
Subjects received JNJ-49095397 400 µg capsule oral inhalation once daily using dry powder inhaler for 12 Weeks. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
JNJ-49095397
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder, hard capsule
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Routes of administration |
Inhalation use
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Dosage and administration details |
Subjects received JNJ-49095397 400 µg once daily by using a dry powder inhaler for 12 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Subjects received Placebo capsule oral inhalation once daily using dry powder inhaler for 12 Weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
JNJ-49095397
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Reporting group description |
Subjects received JNJ-49095397 400 µg capsule oral inhalation once daily using dry powder inhaler for 12 Weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Subjects received Placebo capsule oral inhalation once daily using dry powder inhaler for 12 Weeks. | ||
Reporting group title |
JNJ-49095397
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Reporting group description |
Subjects received JNJ-49095397 400 µg capsule oral inhalation once daily using dry powder inhaler for 12 Weeks. |
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End point title |
Change From Baseline in preBD (before taking an inhaled bronchodilator) Percent-predicted Forced Expiratory Volume in one Second (FEV1) at Week 12 | ||||||||||||||||||
End point description |
FEV1 is the amount of air that can be forcibly exhaled in one second after a maximal inhalation. FEV1 will be measured by spirometry. A positive change from baseline in FEV1 indicates improvement in lung function. The data are shown in two ways in the 'end point values' table below. The first display is 'per cent predicted' where the absolute value of FEV1 (in Liters) is compared to a normal population of the same age, height and gender. The second value displayed is change from baseline at week 12 in per cent predicted which is the primary endpoint. The modified intent-to-treat (mITT) analysis set included all randomized subjects who received at least one dose of study agent and had at least 1 post treatment efficacy measurement. Here, ‘n’ signifies number of subjects analyzed for this endpoint at given timepoint.
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End point type |
Primary
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End point timeframe |
Baseline to Week 12
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||||||||
Comparison groups |
Placebo v JNJ-49095397
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.838 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
Least square (LS) mean difference | ||||||||||||||||||
Point estimate |
0.17
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Confidence interval |
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level |
90% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-1.18 | ||||||||||||||||||
upper limit |
1.51 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.815
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End point title |
Change From Baseline in Postbronchodilator (postBD, after taking an inhaled bronchodilator) Percent-Predicted FEV1 at Week 12 | ||||||||||||||||||
End point description |
FEV1 is the amount of air that can be forcibly exhaled in one second after a maximal inhalation. FEV1 will be measured by spirometry. A positive change from baseline in FEV1 indicates improvement in lung function. The data are shown in two ways in the 'end point values' table below. The first display is 'per cent predicted' where the absolute value of FEV1 (in Liters) is compared to a normal population of the same age, height and gender. The second value displayed is change from baseline at week 12 in per cent predicted which is the primary endpoint. The mITT analysis set included all randomized subjects who received at least one dose of study agent and had at least 1 post treatment efficacy measurement. Here, ‘n’ signifies number of subjects analyzed for this endpoint at given timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline to Week 12
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||||||||
Comparison groups |
Placebo v JNJ-49095397
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.894 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||
Point estimate |
0.1
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Confidence interval |
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level |
90% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-1.14 | ||||||||||||||||||
upper limit |
1.35 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.754
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End point title |
Change From Baseline in Weekly Average Number of Occasions in a day That Rescue Medication is Used at Week 12 | ||||||||||||||||||
End point description |
Use of inhaled rescue medication (expressed as the number of occasions) taken on a schedule and/or for control of symptoms will be recorded twice daily. The mITT analysis set included all randomized subjects who received at least one dose of study agent and had at least 1 post treatment efficacy measurement. Here, ‘n’ signifies number of subjects analyzed for this endpoint at given timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline to Week 12
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||||||||
Comparison groups |
Placebo v JNJ-49095397
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.407 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||
Point estimate |
-0.18
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Confidence interval |
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level |
90% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-0.53 | ||||||||||||||||||
upper limit |
0.18 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.213
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End point title |
Change From Baseline in Exacerbations of Chronic Pulmonary Disease Tool-Respiratory Symptoms (E-RS) Total Score at Week 12 | ||||||||||||||||||
End point description |
E-RS is an 11-items respiratory system scoring algorithm to assess the severity of respiratory symptoms in participants with COPD. Each item has either 5 or 6 response options. Higher score indicates more severe COPD. The mITT analysis set included all randomized subjects who received at least 1 dose of study agent and had at least 1 post treatment efficacy measurement. Here, ‘n’ signifies number of subjects analyzed for this endpoint at given timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline to Week 12
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||||||||
Comparison groups |
Placebo v JNJ-49095397
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.363 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||
Point estimate |
-0.51
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Confidence interval |
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level |
90% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-1.43 | ||||||||||||||||||
upper limit |
0.41 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.557
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End point title |
Change From Baseline in the Total Score of the St. George's Respiratory Questionnaire for COPD Subjects (SGRQ-C) at Week 12 | ||||||||||||||||||
End point description |
SGRQ-C is a 40-item questionnaire designed to measure health impairment in participants with COPD. SGRQ-C is divided into two components: 1) symptoms, 2) activity & impacts. Total SGRQ-C score ranges from 0 (best) and 100 (worst). Higher scores indicate greater health impairment. The mITT analysis set included all randomized subjects who received at least 1 dose of study agent and had at least one post treatment efficacy measurement. Here, ‘n’ signifies number of subjects analyzed for this endpoint at given timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline to week 12
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||||||||
Comparison groups |
Placebo v JNJ-49095397
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.111 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||
Point estimate |
2.47
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Confidence interval |
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level |
90% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-0.08 | ||||||||||||||||||
upper limit |
5.02 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.544
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End point title |
Number of Subjects With Adverse Events | |||||||||
End point description |
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
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End point type |
Secondary
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End point timeframe |
Up to Week 16
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Baseline to follow up (up to Week 16)
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
JNJ-49095397 400µg
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Reporting group description |
Daily inhalation of JNJ-49095397 400 µg for 12 weeks | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PLACEBO
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Reporting group description |
Daily inhalation of Placebo for 12 weeks | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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21 May 2013 |
The amendment includes the following substantial changes: The reference was removed to RVH008 (internal study designation) as alternate name of study to avoid confusion. Text was clarified indicating that the assessments at Study Visit 7 should be performed in the event of early withdrawal from the study. The safety follow-up electrocardiogram (ECG) was moved from Study Visit 8 to Study Visit 7. It updated and clarified text on nonclinical safety pharmacology, and nonclinical genotoxicity, updated text to reflect completed clinical studies and data, and update the dose rationale. Clarified text on summary of safety from clinical studies, removed unnecessary assessment for inventory of study agent at Study Visit 8. Clarification of text on inclusion criterion and reporting for subjects with laboratory values outside normal reference ranges during screening and clarification of inclusion criterion text on use of contraception. The text was clarified on changes to background medications and for storage conditions. |
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10 Oct 2013 |
In a subset of consenting subjects in selected countries and sites, additional PK blood samples were added to the study procedures at the week 8 study visit. Prior scheduled PK assessments were adjusted in this subset. The text was clarified on exclusion criteria regarding previous episodes of COPD exacerbations. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |