Clinical Trial Results:
A randomised, double-blind, placebo-controlled, phase 2 trial investigating the safety and efficacy of C21 in hospitalised subjects with COVID-19 infection not requiring mechanical ventilation
Summary
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EudraCT number |
2020-001502-38 |
Trial protocol |
GB |
Global end of trial date |
13 Oct 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Apr 2021
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First version publication date |
30 Apr 2021
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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 |
VP-C21-006
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04452435 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Vicore Pharma AB
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Sponsor organisation address |
Kronhusgatan 11, Göteborg, Sweden, SE-411 05
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Public contact |
Anne Katrine Cohrt, Vicore Pharma AB, +45 2011 1391, anne-katrine.cohrt@vicorepharma.com
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Scientific contact |
Carl-Johan Dalsgaard, Vicore Pharma AB, +46 70 975 98 63, carl-johan.dalsgaard@vicorepharma.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 |
18 Dec 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 Oct 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Oct 2020
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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 |
To investigate the efficacy of C21 200 mg daily dose (100 mg b.i.d.) on COVID-19 infection not requiring mechanical ventilation
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Protection of trial subjects |
None.
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Background therapy |
All subject received standard of care as background therapy. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 May 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 |
India: 206
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Worldwide total number of subjects |
206
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EEA total number of subjects |
0
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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) |
186
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From 65 to 84 years |
20
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85 years and over |
0
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Recruitment
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Recruitment details |
The trial planned to enrol 150 subjects. The 106 subjects randomised were all recruited at sites in India. As the number of subjects randomised was considered sufficient to meet the statistical demands of the trial, enrolment was stopped prematurely. This ensured that trial results could be available in a timely manner. | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
206 subjects were enrolled. 96 of the enrolled subjects were screening failures because inclusion criteria 4 (CRP ≥50 and ≤150 mg/L) was not met. 2 enrolled subjects decided to withdraw from the trial before randomisation. 2 subjects died before randomisation (pneumonia). The remaining 106 subjects were randomised to trial treatment | |||||||||||||||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
206 | |||||||||||||||||||||||||||
Number of subjects completed |
106 | |||||||||||||||||||||||||||
Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Screening failure: 96 | |||||||||||||||||||||||||||
Reason: Number of subjects |
Adverse event, serious fatal: 2 | |||||||||||||||||||||||||||
Reason: Number of subjects |
Consent withdrawn by subject: 2 | |||||||||||||||||||||||||||
Period 1
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Period 1 title |
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, Carer | |||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo treatment | |||||||||||||||||||||||||||
Arm description |
Oral placebo treatment twice daily for 7 days | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Reference treatment (placebo)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
100 mg twice daily (BID) for 7 days
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Arm title
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C21 treatment | |||||||||||||||||||||||||||
Arm description |
Oral C21 treatment of 100 mg twice daily for 7 days | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
C21
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Investigational medicinal product code |
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Other name |
Compound 21, VP01
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
100 mg twice daily (BID) for 7 days
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 206 subjects were enrolled in the trial but only 106 subjects were randomised and were included in the overall or baseline period. |
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Baseline characteristics reporting groups
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Reporting group title |
Placebo treatment
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Reporting group description |
Oral placebo treatment twice daily for 7 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
C21 treatment
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Reporting group description |
Oral C21 treatment of 100 mg twice daily for 7 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The full analysis set (FAS) consisted of all subjects who were randomized and received at least 1 dose of IMP and who had at least 1 post-baseline assessment of efficacy.
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Subject analysis set title |
Per protocol analysis set
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The per-protocol analysis set (PPAS) was a subset of the FAS and consisted of all subjects without any major protocol deviations that were judged to compromise the analysis of the data.
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End points reporting groups
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Reporting group title |
Placebo treatment
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Reporting group description |
Oral placebo treatment twice daily for 7 days | ||
Reporting group title |
C21 treatment
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Reporting group description |
Oral C21 treatment of 100 mg twice daily for 7 days | ||
Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The full analysis set (FAS) consisted of all subjects who were randomized and received at least 1 dose of IMP and who had at least 1 post-baseline assessment of efficacy.
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Subject analysis set title |
Per protocol analysis set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The per-protocol analysis set (PPAS) was a subset of the FAS and consisted of all subjects without any major protocol deviations that were judged to compromise the analysis of the data.
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End point title |
Change From Baseline in C-reactive Protein (CRP) After Treatment With C21 200 mg Daily Dose (100 mg b.i.d.) | ||||||||||||
End point description |
Change in C-reactive protein (CRP) from baseline to the average of the last two assessments in the treatment period.
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End point type |
Primary
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End point timeframe |
Treatment period of 7 days
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Statistical analysis title |
Primary endpoint analysis | ||||||||||||
Comparison groups |
Placebo treatment v C21 treatment
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Number of subjects included in analysis |
91
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [1] | ||||||||||||
P-value |
= 0.4891 [2] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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Notes [1] - The null hypothesis was that the treatments were equivalent and was to be rejected in favour of the alternative hypothesis that a treatment difference existed, if the probability of the null hypothesis being true was less than 10%. [2] - The ratio of adjusted treatment means was 0.85 (90% CI: 0.57, 1.26; p=0.4891), indicating that the null hypothesis could not be rejected. |
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Statistical analysis title |
Subgroup analysis - use of oxygen at baseline | ||||||||||||
Statistical analysis description |
A subgroup analyses was performed in subjects with supplemental oxygen use at baseline.
A total of 26 subjects in the C21 group and 27 in the placebo group were included in the
analysis of change in CRP from baseline to the mean of the last 2 non-missing scheduled
assessments during the treatment period by baseline supplemental oxygen use.
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Comparison groups |
Placebo treatment v C21 treatment
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Number of subjects included in analysis |
91
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [3] | ||||||||||||
P-value |
= 0.0881 [4] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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Notes [3] - The null hypothesis was that the treatments were equivalent and was to be rejected in favour of the alternative hypothesis that a treatment difference existed, if the probability of the null hypothesis being true was less than 10%. [4] - The ratio of adjusted treatment means was 0.59, the 90% CI did not span 1.0 (0.35, 0.98); and the p-value was less than 0.1 (p=0.0881) indicating a statistically significant difference between the groups. |
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Statistical analysis title |
Subgroup analysis - no oxygen use at baseline | ||||||||||||
Statistical analysis description |
A total of 19 (86.4%) subjects with no supplemental
oxygen use at baseline in the C21 group and 19 (82.6%) subjects in the
placebo group were included in the analysis of change in CRP by baseline supplemental
oxygen use.
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Comparison groups |
C21 treatment v Placebo treatment
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Number of subjects included in analysis |
91
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.6285 [5] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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Notes [5] - The ratio of adjusted treatment means was 1.20 (90% CI: 0.64, 2.26; p=0.6285), indicating no statistically significant difference between the groups. |
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Statistical analysis title |
Subgroup analysis - age ≤ median | ||||||||||||
Statistical analysis description |
A total of 20 (87.0%) subjects of median age (54 years) or lower at baseline in the
C21 group and 26 (83.9%) in the placebo group were included in the analysis of
change in CRP from baseline to the mean of the last 2 non-missing scheduled
assessments during the treatment period by baseline age category.
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Comparison groups |
Placebo treatment v C21 treatment
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Number of subjects included in analysis |
91
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.5978 [6] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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Notes [6] - The ratio of adjusted treatment means was 0.85 (90% CI: 0.51, 1.42; p=0.5978), indicating no statistically significant difference between the treatment groups. |
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Statistical analysis title |
Subgroup analysis - age > median | ||||||||||||
Statistical analysis description |
For subjects above median age (54 years) at baseline, a total of 25 (89.3%) subjects in the
C21 group and 20 (83.3%) subjects in the placebo group were included in
the analysis of change in CRP by baseline age category.
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Comparison groups |
Placebo treatment v C21 treatment
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Number of subjects included in analysis |
91
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.3109 [7] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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Notes [7] - The ratio of adjusted treatment means was 0.70 (90% CI: 0.39, 1.26; p=0.3109), indicating no statistically significant difference between the treatment groups. |
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Statistical analysis title |
Subgroup analysis by sex - women | ||||||||||||
Statistical analysis description |
A total of 12 (92.3%) women
in the C21 group and 10 (76.9%) women in the placebo group were
included in the analysis of change in CRP by sex.
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Comparison groups |
Placebo treatment v C21 treatment
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Number of subjects included in analysis |
91
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.0923 [8] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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Notes [8] - The ratio of adjusted treatment means was 0.38, the 90% CI did not span 1.0 (90% CI: 0.14, 0.98) and the p-value was less than 0.1 (p=0.0923), indicating a statistically significant difference between the groups |
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Statistical analysis title |
Subgroup analysis by sex - men | ||||||||||||
Statistical analysis description |
A total of 33 (86.8%) men in the C21 group and 36 (85.7%) men in the
placebo group were included in the analysis of change in CRP from baseline to the mean
of the last 2 non-missing scheduled assessments during the treatment period by sex.
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Comparison groups |
C21 treatment v Placebo treatment
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Number of subjects included in analysis |
91
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.7134 [9] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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Notes [9] - The ratio of adjusted treatment means was 1.10 (90% CI: 0.71, 1.71; p=0.7134), indicating no statistically significant difference between the treatments. |
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Statistical analysis title |
Subgroup analysis by baseline CRP value ≥ median | ||||||||||||
Statistical analysis description |
A total of 22 (100.0%) subjects in the C21
group and 24 (100.0%) subjects in the placebo group with median CRP values or higher at baseline were included in the analysis.
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Comparison groups |
Placebo treatment v C21 treatment
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Number of subjects included in analysis |
91
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.9374 [10] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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Notes [10] - The ratio of adjusted treatment means was 1.03 (90% CI: 0.58, 1.82; p=0.9374), 0.9374), indicating no statistically significant difference between the treatment groups. |
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Statistical analysis title |
Subgroup analysis by baseline CRP value < median | ||||||||||||
Statistical analysis description |
A total of 24 (96.0%) subjects with CRP levels lower than median at baseline in the
C21 group and 21 (100.0%) in the placebo group were included in the analysis of
change in CRP from baseline to the mean of the last 2 non-missing scheduled
assessments during the treatment period by baseline CRP category.
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Comparison groups |
Placebo treatment v C21 treatment
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Number of subjects included in analysis |
91
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.22444 [11] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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Notes [11] - The ratio in adjusted treatment means was 0.68 (90% CI: 0.40, 1.15; p=0.2244), indicating no statistically significant difference between the treatment groups. |
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End point title |
Change from baseline in body temperature | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Treatment period of 7 days
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Statistical analysis title |
Secondary endpoint analysis - body temperature | ||||||||||||
Comparison groups |
Placebo treatment v C21 treatment
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Number of subjects included in analysis |
105
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [12] | ||||||||||||
P-value |
= 0.0492 [13] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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Notes [12] - The null hypothesis was that the treatments were equivalent and was to be rejected in favour of the alternative hypothesis that a treatment difference existed, if the probability of the null hypothesis being true was less than 10% [13] - The difference of 0.23°C in adjusted treatment means between the groups was statistically significant (90% CI: 0.04, 0.42; p=0.0492). |
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End point title |
Change from baseline in IL-6 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Treatment period of 7 days
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Statistical analysis title |
Secondary endpoint analysis- IL-6 | ||||||||||||
Comparison groups |
Placebo treatment v C21 treatment
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Number of subjects included in analysis |
65
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [14] | ||||||||||||
P-value |
= 0.9923 [15] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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Notes [14] - The null hypothesis was that the treatments were equivalent and was to be rejected in favour of the alternative hypothesis that a treatment difference existed, if the probability of the null hypothesis being true was less than 10%. [15] - The ratio of adjusted treatment means was 1.00 (90% CI: 0.61, 1.66; p=0.9923), indicating no statistically significant difference between the treatment groups. |
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End point title |
Change from baseline in IL-10 | ||||||||||||
End point description |
Change in IL-10 from baseline to the average of the last two assessments during the treatment period
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End point type |
Secondary
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End point timeframe |
Treatment period of 7 days
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Statistical analysis title |
Secondary endpoint analysis - IL-10 | ||||||||||||
Comparison groups |
Placebo treatment v C21 treatment
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Number of subjects included in analysis |
76
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Analysis specification |
Pre-specified
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||||||||||||
Analysis type |
equivalence [16] | ||||||||||||
P-value |
= 0.5355 [17] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|||||||||||||
Notes [16] - The null hypothesis was that the treatments were equivalent and was to be rejected in favour of the alternative hypothesis that a treatment difference existed, if the probability of the null hypothesis being true was less than 10%. [17] - The ratio of adjusted treatment means was 0.90 (90% CI: 0.68, 1.19; p=0.5355), indicating no statistically significant difference between the treatment groups. |
|
|||||||||||||
End point title |
Change from baseline in TNF | ||||||||||||
End point description |
Change in TNF from baseline to the average of the last two assessments during the treatment period.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in TNF from baseline to the average of the last two assessments during the treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Secondary endpoint analysis - TNF | ||||||||||||
Comparison groups |
Placebo treatment v C21 treatment
|
||||||||||||
Number of subjects included in analysis |
92
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [18] | ||||||||||||
P-value |
= 0.4738 [19] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|||||||||||||
Notes [18] - The null hypothesis was that the treatments were equivalent and was to be rejected in favour of the alternative hypothesis that a treatment difference existed, if the probability of the null hypothesis being true was less than 10%. [19] - The ratio of adjusted treatment means was 0.90 (90% CI: 0.72, 1.14; p=0.4738), indicating no statistically significant difference between the treatment groups. |
|
|||||||||||||
End point title |
Change from baseline in CA125 | ||||||||||||
End point description |
Change in CA125 from baseline to the average of the last two assessments in the treatment period
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Treatment period of 7 days
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Secondary endpoint analysis - CA125 | ||||||||||||
Comparison groups |
Placebo treatment v C21 treatment
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [20] | ||||||||||||
P-value |
= 0.9418 [21] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|||||||||||||
Notes [20] - The null hypothesis was that the treatments were equivalent and was to be rejected in favour of the alternative hypothesis that a treatment difference existed, if the probability of the null hypothesis being true was less than 10%. [21] - The ratio of adjusted treatment means was 0.99 (90% CI: 0.84, 1.17; p=0.9418), indicating no statistically significant difference between the treatment groups. |
|
|||||||||||||
End point title |
Change from baseline in ferritin | ||||||||||||
End point description |
Change in ferritin from baseline to the average of the last two assessments during the treatment period.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Treatment period of 7 days
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Secondary endpoint analysis - ferritin | ||||||||||||
Comparison groups |
C21 treatment v Placebo treatment
|
||||||||||||
Number of subjects included in analysis |
93
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [22] | ||||||||||||
P-value |
= 0.9733 [23] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
|||||||||||||
Notes [22] - The null hypothesis was that the treatments were equivalent and was to be rejected in favour of the alternative hypothesis that a treatment difference existed, if the probability of the null hypothesis being true was less than 10%. [23] - The ratio of adjusted treatment means was 1.00 (90% CI: 0.85, 1.19; p=0.9733), indicating no statistically significant difference between the treatment groups. |
|
||||||||||
End point title |
Number of subjects not in need of oxygen supply | |||||||||
End point description |
Number of subjects not in need of oxygen supply at the end of treatment
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Treatment period of 7 days
|
|||||||||
|
||||||||||
Statistical analysis title |
Number of subjects not in need of oxygen | |||||||||
Comparison groups |
Placebo treatment v C21 treatment
|
|||||||||
Number of subjects included in analysis |
106
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
equivalence [24] | |||||||||
P-value |
= 0.0568 [25] | |||||||||
Method |
Regression, Logistic | |||||||||
Confidence interval |
||||||||||
Notes [24] - The null hypothesis was that the treatments were equivalent and was to be rejected in favour of the alternative hypothesis that a treatment difference existed, if the probability of the null hypothesis being true was less than 10% [25] - The odds ratio for C21 versus placebo was 2.20, the 90% CI did not span 1.0 (90% CI: 1.11, 4.35) and the p-value was less than 0.1 (p=0.0568), showing a statistically significant difference in favour of C21. |
|
||||||||||
End point title |
Number of subjects not in need of mechanical invasive or non-invasive ventilation | |||||||||
End point description |
Number of subjects not in need of mechanical invasive or non-invasive ventilation during the treatment period.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Treatment period of 7 days
|
|||||||||
|
||||||||||
Statistical analysis title |
Secondary endpoint analysis - ventilation | |||||||||
Comparison groups |
Placebo treatment v C21 treatment
|
|||||||||
Number of subjects included in analysis |
106
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
equivalence [26] | |||||||||
P-value |
= 0.6088 [27] | |||||||||
Method |
Regression, Logistic | |||||||||
Confidence interval |
||||||||||
Notes [26] - The null hypothesis was that the treatments were equivalent and was to be rejected in favour of the alternative hypothesis that a treatment difference existed, if the probability of the null hypothesis being true was less than 10%. [27] - The odds ratio for 21 versus placebo was 1.89, indicating no statistically significant difference between the treatment groups (90% CI: 0.25, 14.52; p=0.6088. |
|
|||||||||||||
End point title |
Time to need of mechanical invasive or non-invasive ventilation | ||||||||||||
End point description |
Time to need of mechanical invasive or non-invasive ventilation during treatment period.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Treatment period of 7 days
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Secondary endpoint analysis - time to ventilation | ||||||||||||
Comparison groups |
Placebo treatment v C21 treatment
|
||||||||||||
Number of subjects included in analysis |
3
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [28] | ||||||||||||
P-value |
= 0.5757 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|||||||||||||
Notes [28] - The null hypothesis was that the treatments were equivalent and was to be rejected in favour of the alternative hypothesis that a treatment difference existed, if the probability of the null hypothesis being true was less than 10%. |
|
|||||||||||||
End point title |
Time on oxygen supply (for those not needing mechanical invasive or non-invasive ventilation) | ||||||||||||
End point description |
Time on oxygen supply during the treatment period (for those not needing mechanical invasive or non-invasive
ventilation)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Treatment period of 7 days
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Secondary endpoint analysis - time on oxygen | ||||||||||||
Comparison groups |
Placebo treatment v C21 treatment
|
||||||||||||
Number of subjects included in analysis |
106
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [29] | ||||||||||||
P-value |
= 0.8588 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [29] - The null hypothesis was that the treatments were equivalent and was to be rejected in favour of the alternative hypothesis that a treatment difference existed, if the probability of the null hypothesis being true was less than 10%. |
|
||||||||||
End point title |
Adverse Events | |||||||||
End point description |
Adverse events were reported from signing of informed consent until end-of-trial visit and are described under adverse events.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
From signing of informed consent until end-of-trial, 14-17 days
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Oxygen Supplementation at Day 14 | |||||||||
End point description |
Number of subjects requiring oxygen supplementation at Day 14
|
|||||||||
End point type |
Post-hoc
|
|||||||||
End point timeframe |
Follow-up Day 14 (7 days after end-of-treatment)
|
|||||||||
|
||||||||||
Statistical analysis title |
Post-hoc analysis - Day 14 | |||||||||
Comparison groups |
Placebo treatment v C21 treatment
|
|||||||||
Number of subjects included in analysis |
106
|
|||||||||
Analysis specification |
Post-hoc
|
|||||||||
Analysis type |
equivalence [30] | |||||||||
P-value |
= 0.003 [31] | |||||||||
Method |
Chi-squared | |||||||||
Confidence interval |
||||||||||
Notes [30] - The null hypothesis was that the treatments were equivalent and was to be rejected in favour of the alternative hypothesis that a treatment difference existed, if the probability of the null hypothesis being true was less than 10%. [31] - The post hoc analysis showed that 1 (2.0%) subject in the C21 group and 11 (20.0%) subjects in the placebo group were in need of oxygen supplementation at Day 14, with a statistically significant difference between the treatment groups (p=0.003). |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From signing of informed consent until end-of-trial visit, 14-19 days.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
At each visit, the subject was asked about AEs in an objective manner, e.g., “Have you experienced any
problems since the last visit?”
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo treatment
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Oral placebo treatment twice daily for 7 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
C21 treatment
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Oral C21 treatment of 100 mg twice daily for 7 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Frequency threshold for reporting non-serious adverse events: 3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
14 Aug 2020 |
The key changes introduced in protocol version 2.0 (14-Aug-2020) were as follows:
The planned total number of subjects was increased from 100 to 150 (N=75 in each group)
Concomitant medication was allowed to be given according to local SoC (in version 1.0, this had been qualified with ‘If considered unlikely to interfere with IMP or the outcome of the trial’)
The trial was to be conducted at sites globally (version 1.0 was only in the United Kingdom)
With the original sample size of 50 subjects per group, there was an approximate 80% power to detect a true CRP reduction of 30 mg/L in C21-treated subjects compared with placebo. With the new sample size of 75 subjects per group, there was an approximate 80% power to detect a true CRP reduction of 25 mg/L in C21-treated subjects compared with placebo |
||
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 |