Clinical Trial Results:
A Randomized, Double-blind, Placebo-controlled, Crossover Study to Investigate the Mechanism of Action of an Oral Enzyme Treatment with Bromelain, Trypsin and Rutoside versus Placebo in Subjects with OsTeoarthritis (WOBE-SMART)
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Summary
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EudraCT number |
2020-003154-80 |
Trial protocol |
BE |
Global end of trial date |
30 Jan 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Jun 2025
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First version publication date |
29 Jun 2025
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Other versions |
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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 |
2020CLI
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05038410 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Mucos Pharma GmbH & Co KG
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Sponsor organisation address |
Miraustr. 17, Berlin, Germany, 13509
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Public contact |
Artialis, Artialis SA, investigators_clinicaltrials@artialis.com
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Scientific contact |
Artialis, Artialis SA, investigators_clinicaltrials@artialis.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 |
07 Sep 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 Oct 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Jan 2023
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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 this study was to evaluate the pharmacodynamic profile of an oral enzyme treatment with bromelain, trypsin and rutoside in participants with osteoarthritis
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Protection of trial subjects |
Only subjects who were considered eligible by investigators based on the protocol-specific inclusion and exclusion criteria were to be entered in the study.
All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct.
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Background therapy |
All participants had concomitant medication at baseline. The most frequent concomitant medications comprised: paracetamol, ibuprofen, cholecalciferol, acetylsalicylic acid, COVID-19 vaccine, pantoprazole, levothyroxine sodium, bisoprolol, amoxicillin, diclofenac and dextromethorphan | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Dec 2020
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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 |
Belgium: 45
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Worldwide total number of subjects |
45
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EEA total number of subjects |
45
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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) |
24
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From 65 to 84 years |
20
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85 years and over |
1
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Recruitment
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Recruitment details |
Participants were recruited by five study sites across Belgium. Due to challenges in participant recruitment during the global SARS-CoV2 pandemic study timelines were impacted | ||||||||||||||||
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Pre-assignment
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Screening details |
All subjects were screened for eligibility to the trial. Investigator ensure that subjects met all strict inclusion/exclusion criteria. Thus, out of 56 screened patients, 11 patients failed screening. Additionally, one participant (WO-03-002) was randomized, while a screening failure was indicated in “Other reason for drop-out” | ||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (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 | ||||||||||||||||
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Arms
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Arm title
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WOBENZYM® versus Placebo | ||||||||||||||||
Arm description |
Participants were to be randomized to the WOBENZYM® or placebo group to be treated from Visit 0 to 2 (8 weeks of randomized study drug) and then discontinue study drug at Visit 2 and undergo a 4 week washout period. At Visit 3 each participant underwent treatment crossover to continue blinded treatment to Visit 5 or 6 (8- or 24-weeks of randomized study drug). All participants received both WOBENZYM® and placebo in one of the two study arms: WOBENZYM®/placebo or placebo/WOBENZYM® | ||||||||||||||||
Arm type |
Cross over | ||||||||||||||||
Investigational medicinal product name |
WOBENZYM®
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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 |
3 tablets (INN: bromelain, 67.5 mg to 76.5 mg, adjusted to 450 International Pharmaceutical Federation units; trypsin, 32 mg to 48 mg, adjusted to 24 μkat; and rutoside trihydrate, 100 mg) administered morning and evening at least 30 minutes before a meal or 90 minutes after a meal. Total daily dose was 6 tablets
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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 |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
3 tablets administered morning and evening at least 30 minutes before a meal or 90 minutes after a meal. Total daily dose was 6 tablets
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Baseline characteristics reporting groups
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Reporting group title |
WOBENZYM® versus Placebo
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Reporting group description |
Participants were to be randomized to the WOBENZYM® or placebo group to be treated from Visit 0 to 2 (8 weeks of randomized study drug) and then discontinue study drug at Visit 2 and undergo a 4 week washout period. At Visit 3 each participant underwent treatment crossover to continue blinded treatment to Visit 5 or 6 (8- or 24-weeks of randomized study drug). All participants received both WOBENZYM® and placebo in one of the two study arms: WOBENZYM®/placebo or placebo/WOBENZYM® | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
WOBENZYM® versus Placebo
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Reporting group description |
Participants were to be randomized to the WOBENZYM® or placebo group to be treated from Visit 0 to 2 (8 weeks of randomized study drug) and then discontinue study drug at Visit 2 and undergo a 4 week washout period. At Visit 3 each participant underwent treatment crossover to continue blinded treatment to Visit 5 or 6 (8- or 24-weeks of randomized study drug). All participants received both WOBENZYM® and placebo in one of the two study arms: WOBENZYM®/placebo or placebo/WOBENZYM® | ||
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End point title |
Cartilage biomarker sColl2-1 [1] | ||||||||
End point description |
Comparison of change from baseline in cartilage biomarker levels following 8-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Cartilage biomarker sColl2-1NO2 [2] | ||||||||
End point description |
Comparison of change from baseline in cartilage biomarker levels following 8-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Cartilage biomarker sCOMP [3] | ||||||||
End point description |
Comparison of change from baseline in cartilage biomarker levels following 8-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Cartilage biomarker sPIIANP [4] | ||||||||
End point description |
Comparison of change from baseline in cartilage biomarker levels following 8-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Cartilage biomarker uCTXII [5] | ||||||||
End point description |
Comparison of change from baseline in cartilage biomarker levels following 8-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker classical monocytes [6] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker intermediary monocytes [7] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker non-classical monocytes [8] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker total monocytes - CD80-PC7 [9] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker total monocytes - CD86-PE [10] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker total monocytes - CD206-BB515 [11] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker total monocytes - CD163-AF647 [12] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker classical monocytes - CD80-PC7 [13] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker classical monocytes - CD86-PE [14] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker classical monocytes - CD206-BB515 [15] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker classical monocytes - CD163-AF647 [16] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker intermediary monocytes - CD80-PC7 [17] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of
treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker intermediary monocytes - CD86-PE [18] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker intermediary monocytes - CD206-BB515 [19] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
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End point type |
Primary
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End point timeframe |
8-weeks of treatment
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| Notes [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
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| No statistical analyses for this end point | |||||||||
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End point title |
Innate immune response marker intermediary monocytes - CD163-AF647 [20] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Innate immune response marker non-classical monocytes - CD80-PC7 [21] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Innate immune response marker non-classical monocytes - CD86-PE [22] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Innate immune response marker non-classical monocytes - CD206-BB515 [23] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Innate immune response marker non-classical monocytes - CD163-AF647 [24] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Innate immune response marker NLRP3 inflammasome [25] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Innate immune response marker α2-macroglobulin [26] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Systemic inflammatory marker IL-1β [27] | ||||||||
End point description |
Comparison of change from baseline in markers of systemic inflammation following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Systemic inflammatory marker TNFα [28] | ||||||||
End point description |
Comparison of change from baseline in markers of systemic inflammation following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Systemic inflammatory marker IL-6 [29] | ||||||||
End point description |
Comparison of change from baseline in markers of systemic inflammation following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Systemic inflammatory marker IL-10 [30] | ||||||||
End point description |
Comparison of change from baseline in markers of systemic inflammation following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Systemic inflammatory marker IL-4 [31] | ||||||||
End point description |
Comparison of change from baseline in markers of systemic inflammation following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
TGF-β1 [32] | ||||||||
End point description |
Comparison of change from baseline in serum growth factor concentrations following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
TGF-β2 [33] | ||||||||
End point description |
Comparison of change from baseline in serum growth factor concentrations following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
TGF-β3 [34] | ||||||||
End point description |
Comparison of change from baseline in serum growth factor concentrations following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
C-reactive Protein Metabolites (CRPM) [35] | ||||||||
End point description |
Comparison of change from baseline following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Advanced Glycation End Product (AGE) [36] | ||||||||
End point description |
Comparison of change from baseline following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Innate immune response marker classical monocytes % [37] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Innate immune response marker intermediary monocytes % [38] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [38] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Innate immune response marker non-classical monocytes % [39] | ||||||||
End point description |
Comparison of change from baseline in markers of innate immune response following 8 weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
8-weeks of treatment
|
||||||||
| Notes [39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All patients received both WOBENZYM® and Placebo, so a single reporting group is considered. Change from baseline in each patient was analyzed using a general linear mixed model (GLMM) with treatment, period and sequence (i.e. period x treatment) as fixed factors and participant as random factors. Endpoint values provided as least squares mean represent the GLLM estimator |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Knee Pain at rest | ||||||||
End point description |
Comparison of change from baseline following 8- or 24-weeks in knee pain at rest measured by a visual analogue scale (VAS) of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Knee Pain at walking | ||||||||
End point description |
Comparison of change from baseline following 8- or 24-weeks in knee pain at walking measured by a visual analogue scale (VAS) of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Knee function KOOS - Symptoms score | ||||||||
End point description |
Comparison of change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) following 8- or 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Knee function KOOS - Pain score | ||||||||
End point description |
Comparison of change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) following 8- or 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Knee function KOOS- ADL score | ||||||||
End point description |
Comparison of change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) following 8- or 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Knee function KOOS -Sports score | ||||||||
End point description |
Comparison of change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) following 8- or 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Knee function KOOS -Quality of life score | ||||||||
End point description |
Comparison of change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) following 8- or 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Knee function KOOS - Global score | ||||||||
End point description |
Comparison of change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) following 8- or 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Patient Global Assessment of Disease Activity (PGADA) | ||||||||
End point description |
Comparison of change from baseline in Patient Global Assessment of Disease Activity (PGADA) measured by a visual analogue scale (VAS) following 8- or 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Global Physical Activity Parameter (GPA) heart rate | ||||||||
End point description |
Comparison of change from baseline in in global physical activity parameters following 8- or 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Global Physical Activity (GPA) daily number of steps | ||||||||
End point description |
Comparison of change from baseline in in global physical activity parameters following 8- or 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Global Physical Activity (GPA) Climbed stairs | ||||||||
End point description |
Comparison of change from baseline in in global physical activity parameters following 8- or 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Global Physical Activity (GPA) Intensive minutes | ||||||||
End point description |
Comparison of change from baseline in in global physical activity parameters following 8- or 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Global Physical Activity (GPA) Calories burned | ||||||||
End point description |
Comparison of change from baseline in in global physical activity parameters following 8- or 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
WORMS Cartilage - patellofemoral joint | ||||||||
End point description |
Comparison of change from baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) in specific joint parameters following 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
WORMS Cartilage global score | ||||||||
End point description |
Comparison of change from baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) in specific joint parameters following 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
WORMS Bone marrow - patellofemoral joint | ||||||||
End point description |
Comparison of change from baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) in specific joint parameters following 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
WORMS Bone marrow - medial tibiofemoral joint | ||||||||
End point description |
Comparison of change from baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) in specific joint parameters following 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
WORMS Bone marrow - lateral tibiofemoral joint | ||||||||
End point description |
Comparison of change from baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) in specific joint parameters following 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
WORMS Bone marrow global score | ||||||||
End point description |
Comparison of change from baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) in specific joint parameters following 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
WORMS Cyst - patellofemoral joint | ||||||||
End point description |
Comparison of change from baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) in specific joint parameters following 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
WORMS Cyst global score | ||||||||
End point description |
Comparison of change from baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) in specific joint parameters following 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
WORMS Effusion maximal distension of the synovial cavity | ||||||||
End point description |
Comparison of change from baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) in specific joint parameters following 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
WORMS Size of synovial cysts | ||||||||
End point description |
Comparison of change from baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) in specific joint parameters following 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Joint Effusion | ||||||||
End point description |
Comparison of change from baseline following 24-weeks of treatment with WOBENZYM® versus placebo in modified intention-to-treat (mITT) population
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
24-weeks of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||
End point title |
Treatment Responder Rate | ||||||||||
End point description |
Comparison of change from baseline of treatment responder rate, defined as changes in knee pain and/or knee function and/or disease activity, following 8- or 24-weeks of treatment with WOBENZYM® versus placebo in in modified intention-to-treat (mITT) population
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
8- or 24-weeks of treatment
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
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Timeframe for reporting adverse events |
Treatment-emergent AEs were assessed from the start of dosing with study drug (Visit 1) through the entire study
|
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
|
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Reporting groups
|
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Reporting group title |
WOBENZYM
|
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
25 May 2021 |
• Permitted the inclusion of participants taking low-dose (100 mg) aspirin that had no identifiable effect on their bleeding risk based on review of their medical history by the principal investigator.
• Reduced the number of parameters assessed from watch data and specified analysis of mobility data comprising: heart rate, daily number of steps, stairs climbed, intensive activity minutes, and calories burned. It also described the requirement that the participant regularly download data from the activity watch. This reflected clarification of those data considered most pertinent to studying fitness and health in participants with osteoarthritis.
• Removed the requirement to test eccentric 30°S hamstrings during isokinetic analyses. This reflected clarification of those data considered most pertinent to assessing muscle strength in participants with osteoarthritis.
• Allowed for the optional collection of fecal samples for gut microbiome and metabolome analysis. |
||
23 May 2022 |
• Replaced inflammatory aging clock with assessment of AGE biomarkers and CRPM to estimate chronic inflammation and inflammatory age respectively.
• Specified that participants were to attend four or five study visits (up to Visit 5 or 6 respectively). This was due to challenges in participant recruitment during the global SARSCoV2 pandemic that had an associated impact on study timelines. As a result the study drug batch reached its expiry date (on 30 Sep 2022) before Visit 6 for the 6 participants recruited after February 2022. The potential for mitigating the issue by study drug re-supply was compromised by a global shortage at that time of pharmaceutical-grade bromelain. As a result, it was not possible for all participants to complete the study to Visit 6. Consequently, participants recruited after February 2022 were to exit the study at Visit 5 rather than Visit 6 as planned.
• Specified the study duration as 22 to 24 weeks to support the primary objective and 40 weeks to support exploratory objectives. It was specified that participants would undergo an initial 8-week treatment period followed by a second 8-week treatment period for those recruited after February 2022 or 24-week treatment period for those recruited earlier. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
