Clinical Trial Results:
A Randomised, Parallel Arm, Placebo-Controlled, Double-Blind, Study of the Safety and Efficacy of PRX167700 Added to Existing Non-steroidal Anti-inflammatory Therapy in Adults with Moderate-to-Severe Knee Pain Due to Osteoarthritis
Summary
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EudraCT number |
2016-001443-39 |
Trial protocol |
GB HU CZ PL ES |
Global end of trial date |
29 Oct 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Oct 2019
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First version publication date |
23 Oct 2019
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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 |
167700-004CL
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Benevolent AI Cambridge Ltd.
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Sponsor organisation address |
Minerva Building 250, Babraham Research Campus, Cambridge, United Kingdom, CB22 3AT
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Public contact |
Clinical Trial Information, Benevolent AI Cambridge Ltd. (formerly Proximagen Ltd.), +44 1223 497 300, jackie.hunter@benevolent.ai
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Scientific contact |
Clinical Trial Information, Benevolent AI Cambridge Ltd. (formerly Proximagen Ltd.), +44 1223 497 300, jackie.hunter@benevolent.ai
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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 |
29 Oct 2018
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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 |
29 Oct 2018
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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 primary objective of the study was to assess the effect of PRX167700 treatment on knee pain, on a background of stable oral non-steroidal anti-inflammatory drug (NSAID) therapy in subjects with moderate to severe pain caused by osteoarthritis (OA).
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Protection of trial subjects |
Independent ethics committees and institutional review boards: The clinical study protocol, informed consent documents, and any other appropriate study-related documents were reviewed and approved by an independent ethics committee (IEC)/institutional review board (IRB). Protocol amendments for administrative reasons were submitted to the IECs for information only.
Ethical conduct of the study: This study was conducted in accordance with the good clinical practice (GCP) as required by the International Conference on Harmonization (ICH) E6 Guideline for GCP, 1 May 1996 (ICH E6) and ICH E6 (R2), in agreement with the standard operating procedures (SOPs) for clinical investigation and documentation. Compliance with these requirements also constitutes conformity with the ethical principles of the Declaration of Helsinki, and any local regulations were followed appropriately. The Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines were also followed.
Subject information and informed consent: Prior to the conduct of any study-related procedures, informed consent was obtained from all subjects. Before obtaining informed consent, information was given in a language and at a level of complexity understandable to the subject in both oral and written form by the investigator. Each subject had the opportunity to discuss the study and its alternatives with the investigator.
Participation in the study and date of informed consent given by the subject was to be documented appropriately in the subject files.
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Background therapy |
The patients were on a background of stable NSAID therapy. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
26 Jan 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Spain: 13
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Country: Number of subjects enrolled |
United Kingdom: 70
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Country: Number of subjects enrolled |
Czech Republic: 27
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Country: Number of subjects enrolled |
Hungary: 44
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Country: Number of subjects enrolled |
Poland: 48
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Worldwide total number of subjects |
202
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EEA total number of subjects |
202
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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) |
127
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From 65 to 84 years |
75
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85 years and over |
0
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Recruitment
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Recruitment details |
The first subject was enrolled on 26 January 2017 & the last subject follow-up was completed on 29 October 2018. The study was conducted at 30 centres across the UK, Spain, Poland, Hungary & the Czech Republic. Subjects must have had pain in the target knee for ≥14 days per month in the 3 months preceding screening. | |||||||||
Pre-assignment
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Screening details |
The duration per subject was approximately 9 to 12 weeks, including screening (up to 28 days, with a 14-day placebo run-in), treatment (42 days), & follow-up (7 to 10 days) periods. There were 9 study visits. Subjects who completed the placebo run-in & who still met all of the inclusion criteria & none of the exclusion criteria were randomized. | |||||||||
Period 1
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Period 1 title |
Period 1 (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, Monitor, Data analyst, Assessor | |||||||||
Blinding implementation details |
The Interactive Web-Based Response System (IWRS) was programmed with blind breaking instructions. The study blind could be broken if, in the opinion of the investigator, it was in the subject’s best interest to know the study treatment assignment. The date and reason that the blind was broken was recorded in the electronic case report form (eCRF).
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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PRX167700 | |||||||||
Arm description |
PRX167700 400mg oral tablet three times a day. Note: The started and completed information refers to the safety population. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
PRX167700
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
One PRX167700 400mg tablet was taken orally three times a day (6-8 hours apart) with water; each dose was taken within 30 minutes after eating. The tablet was uncoated before the study pause, and film-coated after the study pause.
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Arm title
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Placebo | |||||||||
Arm description |
Placebo oral tablet three times a day. | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
PRX167700
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
One Placebo tablet was taken orally three times a day (6-8 hours apart) with water; each dose was taken within 30 minutes after eating. The tablet was uncoated before the study pause, and film-coated after the study pause.
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Baseline characteristics reporting groups
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Reporting group title |
PRX167700
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Reporting group description |
PRX167700 400mg oral tablet three times a day. Note: The started and completed information refers to the safety population. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo oral tablet three times a day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
PRX167700
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Reporting group description |
PRX167700 400mg oral tablet three times a day. Note: The started and completed information refers to the safety population. | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo oral tablet three times a day. |
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End point title |
WOMAC Pain Score (mITT) | ||||||||||||
End point description |
The primary endpoint was analysed using a MMRM analysis that includes all WOMAC Pain Score changes from baseline through to 6 weeks of treatment. The main comparison was between treatment arms at 6 weeks. Least square mean changes were estimated for PRX167700 and placebo.
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End point type |
Primary
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End point timeframe |
WOMAC Pain Score (mITT) at Visit 8 (Day 42) in mITT population.
Note: The data are presented as LS mean change in WOMAC pain score x 10. These number should be read as - ve numbers.
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Statistical analysis title |
Mixed model repeated measures (MMRM) analysis | ||||||||||||
Statistical analysis description |
The primary endpoint was analysed using a MMRM analysis that includes all WOMAC Pain Score changes from baseline to 1 week through to 6 weeks. These methods have in recent years become the preferred approach to longitudinal analysis because they utilise the observed data efficiently. Moreover, they naturally handle missing data, if the data are missing at random, in a way that produces unbiased estimates of the treatment effect.
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Comparison groups |
Placebo v PRX167700
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Number of subjects included in analysis |
182
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||
P-value |
= 0.563 [2] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-0.3
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.3 | ||||||||||||
upper limit |
0.7 | ||||||||||||
Notes [1] - For the primary efficacy endpoint, the null (H0) and alternative (H1) hypotheses of the study were as follows: • H0: PRX167700 and placebo do not differ in their change from baseline in the WOMAC Pain Score at Visit 8 (Day 42). • H1: PRX167700 and placebo differ in their change from baseline in the WOMAC Pain Score at Visit 8 (Day 42). [2] - Nil. |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Adverse events were collected throughout the study including the follow-up visit.
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Adverse event reporting additional description |
Adverse event information was collected at each study visit.
The information shown below is for Safety Population. The non-serious adverse events with frequency threshold 5% or more are reported.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.1
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Reporting groups
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Reporting group title |
PRX167700
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Reporting group description |
PRX167700 400mg oral tablet three times a day. | |||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo oral tablet three times a day. | |||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: There were no non-serious AEs over the 5% threshold for a given preferred term. In the safety population, the incidence of AEs was similar in both study arms: 40/101 (39.6%) of subjects had AEs during the double blind period in the PRX167700 arm versus 43/101 (42.6%) in the placebo arm. The total number of non-serious AE occurrences in PRX167700 and Placebo arms were 69 and 74 respectively. |
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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? No | |||||||
Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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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. | |||||||
The data under population of trial subjects are for treated subjects. Overall, a total of 520 subjects were enrolled in the study, of which 61.0% were screen failures. A total of 203 subjects were randomised, of which 202 received study drug. |