Safety and Efficacy of C21 in Subjects With COVID-19

• Sponsor: Vicore Pharma AB (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04452435
• Collaborator: Orphan Reach (Other)
• Enrollment: 206
• Locations: 9
• Arms: 2
• Actual Duration (Months): 2.8
• Patients Per Site: 22.9
• Patients Per Site Per Month: 8.3

Study Details

Study Description

Brief Summary

This is a randomised, double-blind, placebo-controlled phase 2 trial investigating the safety and efficacy of C21 in subjects who are hospitalised with COVID-19 infection, but not in need of mechanical invasive or non-invasive ventilation.

In total, approximately 100 subjects will be enrolled and randomised to receive twice daily oral administration of either standard of care (SoC) + placebo (N=50) or SoC + C21 (N=50). Subjects will be treated for 7 days.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: C21; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 206 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jul 21, 2020
• Actual Primary Completion Date: Oct 13, 2020
• Actual Study Completion Date: Oct 13, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: C21 100 mg twice daily Oral C21 treatment 100 mg twice daily for 7 days	Drug: C21; C21
Placebo Comparator: Placebo Oral placebo treatment 100 mg twice daily for 7 days	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in C-reactive Protein (CRP) After Treatment With C21 200 mg Daily Dose (100 mg b.i.d.) [Treatment period of 7 days (Day 1 to Day 8)]

   Change in C-reactive protein (CRP) from baseline to the average of the last two assessments in the treatment period

Secondary Outcome Measures

1. Change From Baseline in Body Temperature [Treatment period of 7 days ((Day 1 to Day 8)]

   Change in body temperature from baseline to the average of the last two assessments in the treatment period

2. Change From Baseline in IL-6 [Treatment period of 7 days (Day 1 to Day 8)]

   Change in IL-6 from baseline to the average of the last two assessments during the treatment period

3. Change From Baseline in IL-10 [Treatment period of 7 days (Day 1 to Day 8)]

   Change in IL-10 from baseline to the average of the last two assessments during the treatment period

4. Change From Baseline in TNF [Treatment period of 7 days (Day 1 to Day 8)]

   Change in TNF from baseline to the average of the last two assessments during the treatment period.

5. Change From Baseline in CA125 [Treatment period of 7 days (Day 1 to Day 8)]

   Change in CA125 from baseline to the average of the last two assessments in the treatment period

6. Change From Baseline in Ferritin [Treatment period of 7 days (Day 1 to Day 8)]

   Change in Ferritin from baseline to the average of the last two assessments during the treatment period.

7. Number of Subjects Not in Need of Oxygen Supply [End-of treatment, Day 7 or 8]

   Number of subjects not in need of oxygen supply at the end of treatment

8. Number of Subjects Not in Need of Mechanical Invasive or Non-invasive Ventilation [Treatment period of 7 days (Day 1 to Day 8)]

   Number of subjects not in need of mechanical invasive or non-invasive ventilation during the treatment period

9. Time to Need of Mechanical Invasive or Non-invasive Ventilation [Treatment period of 7 days]

   Time to need of mechanical invasive or non-invasive ventilation during treatment period

10. Time on Oxygen Supply (for Those Not Needing Mechanical Invasive or Non-invasive Ventilation) [Treatment period of 7 days (Day 1 to Day 8)]

    Time on oxygen supply during the treatment period (for those not needing mechanical invasive or non-invasive ventilation)

11. Adverse Events [Day 1 to end-of-trial (Visit 9)]

    Adverse events were reported from signing of informed consent until end-of-trial visit. No AEs were reported from signing of informed consent until randomization, except for 2 fatal SAEs described under Adverse events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Written informed consent, consistent with ICH-GCP R2 and local laws, obtained before the initiation of any trial related procedure

2. Diagnosis of coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test < 4 days before Visit 1 with signs of an acute respiratory infection

3. Age > 18 and < 70 years

4. CRP > 50 and < 150 mg/l

5. Admitted to a hospital or controlled facility (home quarantine is not sufficient)

6. In the opinion of the Investigator, the subject will be able to comply with the requirements of the protocol

Exclusion Criteria:

1. Any previous experimental treatment for COVID-19

2. Need for mechanical invasive or non-invasive ventilation

3. Concurrent respiratory disease such as COPD (chronic obstructive pulmonary disease), IPF and/or intermittent, persistent or more severe asthma requiring daily therapy or any subjects that have had an asthma flare requiring corticosteroids in the 4 weeks (28 days) prior to COVID-19 diagnosis

4. Participation in any other interventional trial within 3 months prior to Visit 1

5. Any of the following findings at Visit 1:

• Positive results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb) or human immunodeficiency virus 1+2 antigen/antibody (HIV 1+2 Ag/Ab

• Positive pregnancy test (see Section 8.2.3)

1. Clinically significant abnormal laboratory value at Visit 1 indicating a potential risk for the subject if enrolled in the trial as evaluated by the Investigator

2. Concurrent serious medical condition with special attention to cardiac or ophthalmic conditions (e.g. contraindications to cataract surgery), which in the opinion of the Investigator makes the subject inappropriate for this trial

3. Malignancy within the past 3 years with the exception of in situ removal of basal cell carcinoma and cervical intraepithelial neoplasia grade I

4. Treatment with any of the medications listed below within 1 week prior to Visit 1:

5. Strong Cytochrome p450 (CYP) 3A4 inducers (e.g. rifampicin, phenytoin, St. John's Wort, phenobarbital, rifabutin, carbamazepine, anti HIV drugs, barbiturates)

6. Warfarin

7. Pregnant or breast-feeding female subjects

8. Female subjects of childbearing potential not willing to use contraceptive methods as described in Section 5.3.1

9. Male subjects not willing to use contraceptive methods as described in Section 5.3.1

10. Subjects known or suspected of not being able to comply with this trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Medicine, Civil Hospital and B J Medical College	Ahmadabad	Gujarat	India	380016
2	Infectious Disease, Metas Adventist Hospital	Surat	Gujarat	India	395001
3	Clinical Research Department, Basement, Unity Trauma Centre and ICU (Unity Hospital	Surat	Gujarat	India	395010
4	First Floor Clinical Research Department Rhythm Heart Institute	Vadodara	Gujarat	India	290022
5	Internal Medicine S.L. Raheja Hospital	Mumbai	Maharashtra	India	400016
6	Department of Medicine, Government Medical College and Hospital	Nagpur	Maharashtra	India	440003
7	Neuro Critical Care, Grant Medical Foundation Ruby Hall Clinic	Pune	Maharashtra	India	411001
8	Department of Medicine, Noble Hospitals Pvt. Ltd	Pune	Maharashtra	India
9	Respiratory Medicine, University College Hospital	London		United Kingdom	WC1E 6BT

Sponsors and Collaborators

• Vicore Pharma AB
• Orphan Reach

Investigators

• Principal Investigator: Joanna Porter, MD, Respiratory Medicine, University College Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan: Study Protocol - Aug 14, 2020
• Statistical Analysis Plan: Statistical Analysis Plan - Sep 10, 2020

More Information

Publications

None provided.

• Responsible Party: Vicore Pharma AB
• ClinicalTrials.gov Identifier: NCT04452435
• Other Study ID Numbers: VP-C21-006; 2020-001502-38
• First Posted: Jun 30, 2020
• Last Update Posted: Jun 23, 2021
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Vicore Pharma AB: COVID-19
• Additional relevant MeSH terms: COVID-19

Study Results

Participant Flow

Pre-assignment Detail	96 enrolled subjects were screening failures because inclusion criteria 4 was not met. 2 enrolled subjects decided to withdraw from the trial before randomization. 2 subjects died before randomization (pneumonia). The remaining 106 subjects were randomized to trial treatment.

Arm/Group Title	C21 Treatment	Placebo Treatment
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days
Period Title: Screening
STARTED	51	55
COMPLETED	51	55
NOT COMPLETED	0	0
Period Title: Screening
STARTED	51	55
COMPLETED	45	43
NOT COMPLETED	6	12
Period Title: Screening
STARTED	45	43
COMPLETED	45	42
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	C21 Treatment	Placebo Treatment	Total
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days	Total of all reporting groups
Overall Participants	51	55	106
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	54.3	51.1	52.6
Sex: Female, Male (Count of Participants)
Female	13 25.5%	13 23.6%	26 24.5%
Male	38 74.5%	42 76.4%	80 75.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	51 100%	55 100%	106 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	51 100%	55 100%	106 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
India	51 100%	55 100%	106 100%
Height (cm) [Mean (Full Range) ]
Mean (Full Range) [cm]	166.1	166.0	166.1
Weight (kg) [Mean (Full Range) ]
Mean (Full Range) [kg]	70.1	69.2	69.6
Body mass index (kg/m^2) [Mean (Full Range) ]
Mean (Full Range) [kg/m^2]	25.4	25.1	25.2
Supplemental oxygen use at baseline (Count of Participants)
Count of Participants [Participants]	29 56.9%	32 58.2%	61 57.5%
CRP value ≤ median (Count of Participants)
Count of Participants [Participants]	24 47.1%	22 40%	46 43.4%
CRP value > median (Count of Participants)
Count of Participants [Participants]	21 41.2%	25 45.5%	46 43.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in C-reactive Protein (CRP) After Treatment With C21 200 mg Daily Dose (100 mg b.i.d.)
Description	Change in C-reactive protein (CRP) from baseline to the average of the last two assessments in the treatment period
Time Frame	Treatment period of 7 days (Day 1 to Day 8)

Outcome Measure Data

Analysis Population Description

Full analysis set. A total of 45 subjects in the C21 group and 46 subjects in the placebo group were included in the analysis of the primary endpoint in the FAS. For a number of the excluded subjects, the reason for exclusion from the primary endpoint analysis was that they had no baseline value available.

Arm/Group Title	C21 Treatment	Placebo Treatment
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days
Measure Participants	45	46
Least Squares Mean (90% Confidence Interval) [mg/L]	0.19	0.22

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C21 Treatment, Placebo Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value	=0.4891
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	C21 Treatment, Placebo Treatment
	Comments	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.
	Type of Statistical Test	Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value	=0.0881
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Change From Baseline in Body Temperature
Description	Change in body temperature from baseline to the average of the last two assessments in the treatment period
Time Frame	Treatment period of 7 days ((Day 1 to Day 8)

Outcome Measure Data

Analysis Population Description

Subjects with measurements were included in the analysis for the full analysis set.

Arm/Group Title	C21 Treatment	Placebo Treatment
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days
Measure Participants	51	54
Least Squares Mean (90% Confidence Interval) [°C]	-0.11	-0.34

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C21 Treatment, Placebo Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value	=0.0492
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Change From Baseline in IL-6
Description	Change in IL-6 from baseline to the average of the last two assessments during the treatment period
Time Frame	Treatment period of 7 days (Day 1 to Day 8)

Outcome Measure Data

Analysis Population Description

Subjects with measurements were included in the analysis for the full analysis set.

Arm/Group Title	C21 Treatment	Placebo Treatment
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days
Measure Participants	31	34
Least Squares Mean (90% Confidence Interval) [pg/mL]	0.73	0.73

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C21 Treatment, Placebo Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value	=0.9923
	Comments
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	Change From Baseline in IL-10
Description	Change in IL-10 from baseline to the average of the last two assessments during the treatment period
Time Frame	Treatment period of 7 days (Day 1 to Day 8)

Outcome Measure Data

Analysis Population Description

Subjects with measurements were included in the analysis for the full analysis set.

Arm/Group Title	C21 Treatment	Placebo Treatment
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days
Measure Participants	37	39
Least Squares Mean (90% Confidence Interval) [pg/mL]	0.66	0.73

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C21 Treatment, Placebo Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value	=0.5355
	Comments
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Change From Baseline in TNF
Description	Change in TNF from baseline to the average of the last two assessments during the treatment period.
Time Frame	Treatment period of 7 days (Day 1 to Day 8)

Outcome Measure Data

Analysis Population Description

Subjects with measurements were included in the analysis for the full analysis set.

Arm/Group Title	C21 Treatment	Placebo Treatment
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days
Measure Participants	46	46
Least Squares Mean (90% Confidence Interval) [pg/mL]	0.91	1.01

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C21 Treatment, Placebo Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value	=0.4738
	Comments
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	Change From Baseline in CA125
Description	Change in CA125 from baseline to the average of the last two assessments in the treatment period
Time Frame	Treatment period of 7 days (Day 1 to Day 8)

Outcome Measure Data

Analysis Population Description

Subjects with measurements were included in the analysis for the full analysis set.

Arm/Group Title	C21 Treatment	Placebo Treatment
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days
Measure Participants	46	48
Least Squares Mean (90% Confidence Interval) [u/mL]	1.16	1.17

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C21 Treatment, Placebo Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value	=0.9418
	Comments
	Method	ANCOVA
	Comments

7. Secondary Outcome

Title	Change From Baseline in Ferritin
Description	Change in Ferritin from baseline to the average of the last two assessments during the treatment period.
Time Frame	Treatment period of 7 days (Day 1 to Day 8)

Outcome Measure Data

Analysis Population Description

Subjects with measurements were included in the analysis for the full analysis set.

Arm/Group Title	C21 Treatment	Placebo Treatment
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days
Measure Participants	46	47
Least Squares Mean (90% Confidence Interval) [ng/mL]	0.75	0.74

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C21 Treatment, Placebo Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value	=0.9733
	Comments
	Method	ANCOVA
	Comments

8. Secondary Outcome

Title	Number of Subjects Not in Need of Oxygen Supply
Description	Number of subjects not in need of oxygen supply at the end of treatment
Time Frame	End-of treatment, Day 7 or 8

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	C21 Treatment	Placebo Treatment
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days
Measure Participants	51	55
Count of Participants [Participants]	37 72.5%	30 54.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C21 Treatment, Placebo Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value	=0.0568
	Comments
	Method	Regression, Logistic
	Comments

9. Secondary Outcome

Title	Number of Subjects Not in Need of Mechanical Invasive or Non-invasive Ventilation
Description	Number of subjects not in need of mechanical invasive or non-invasive ventilation during the treatment period
Time Frame	Treatment period of 7 days (Day 1 to Day 8)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	C21 Treatment	Placebo Treatment
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days
Measure Participants	51	55
Count of Participants [Participants]	50 98%	53 96.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C21 Treatment, Placebo Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value	=0.6088
	Comments
	Method	Regression, Logistic
	Comments

10. Secondary Outcome

Title	Time to Need of Mechanical Invasive or Non-invasive Ventilation
Description	Time to need of mechanical invasive or non-invasive ventilation during treatment period
Time Frame	Treatment period of 7 days

Outcome Measure Data

Analysis Population Description

Subjects with measurements were included in the analysis for the full analysis set.

Arm/Group Title	C21 Treatment	Placebo Treatment
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days
Measure Participants	1	2
Mean (Full Range) [hours]	60.0	77.925

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C21 Treatment, Placebo Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value	=0.5757
	Comments
	Method	Log Rank
	Comments

11. Secondary Outcome

Title	Time on Oxygen Supply (for Those Not Needing Mechanical Invasive or Non-invasive Ventilation)
Description	Time on oxygen supply during the treatment period (for those not needing mechanical invasive or non-invasive ventilation)
Time Frame	Treatment period of 7 days (Day 1 to Day 8)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	C21 Treatment	Placebo Treatment
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days
Measure Participants	51	55
Median (Inter-Quartile Range) [days]	5.0	5.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C21 Treatment, Placebo Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value	=0.8588
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

12. Secondary Outcome

Title	Adverse Events
Description	Adverse events were reported from signing of informed consent until end-of-trial visit. No AEs were reported from signing of informed consent until randomization, except for 2 fatal SAEs described under Adverse events.
Time Frame	Day 1 to end-of-trial (Visit 9)

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title	C21 Treatment	Placebo Treatment
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days
Measure Participants	51	55
Count of Participants [Participants]	31 60.8%	37 67.3%

13. Post-Hoc Outcome

Title	Oxygen Supplementation at Day 14
Description	Number of subjects requiring oxygen supplementation at Day 14
Time Frame	Follow-up Day 14 (7 days after end-of-treatment)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	C21 Treatment	Placebo Treatment
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days	Oral placebo treatment twice daily for 7 days
Measure Participants	51	55
Count of Participants [Participants]	1 2%	11 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C21 Treatment, Placebo Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value	=0.003
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	From signing of informed consent until end-of-trial visit, 14-19 days.
Adverse Event Reporting 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?" No AEs were reported from signing of informed consent until randomization except for 2 fatal SAEs.
Arm/Group Title	C21 Treatment		Placebo Treatment		No Treatment (Before Randomization)
Arm/Group Description	Oral C21 treatment 100 mg twice daily for 7 days		Oral placebo treatment twice daily for 7 days		Subjects that were enrolled in the trial but not randomized
All Cause Mortality
	C21 Treatment		Placebo Treatment		No Treatment (Before Randomization)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/51 (2%)		3/55 (5.5%)		2/100 (2%)
Serious Adverse Events
	C21 Treatment		Placebo Treatment		No Treatment (Before Randomization)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/51 (2%)		3/55 (5.5%)		2/100 (2%)
Cardiac disorders
Cardio-respiratory arrest	1/51 (2%)	1	1/55 (1.8%)	1	0/100 (0%)	0
Infections and infestations
COVID-19 pneumonia	0/51 (0%)	0	2/55 (3.6%)	2	2/100 (2%)	2
Other (Not Including Serious) Adverse Events
	C21 Treatment		Placebo Treatment		No Treatment (Before Randomization)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/51 (58.8%)		36/55 (65.5%)		0/100 (0%)
Gastrointestinal disorders
Constipation	0/51 (0%)	0	4/55 (7.3%)	4	4/100 (4%)	4
Investigations
Aspartate aminotransferase increased	6/51 (11.8%)	6	3/55 (5.5%)	4	3/100 (3%)	4
Blood glucose increased	5/51 (9.8%)	7	3/55 (5.5%)	3	3/100 (3%)	3
Interleukin level increased	4/51 (7.8%)	6	4/55 (7.3%)	4	4/100 (4%)	4
Alanine aminotransferase increased	3/51 (5.9%)	3	4/55 (7.3%)	5	4/100 (4%)	5
Serum ferritin increased	5/51 (9.8%)	5	2/55 (3.6%)	2	2/100 (2%)	2
Alpha tumour necrosis factor increased	1/51 (2%)	1	3/55 (5.5%)	3	3/100 (3%)	3
Carbohydrate antigen 125 increased	0/51 (0%)	0	4/55 (7.3%)	4	4/100 (4%)	4
Lymphocyte count decreased	1/51 (2%)	1	3/55 (5.5%)	4	3/100 (3%)	4
Neutrophil count increased	1/51 (2%)	1	3/55 (5.5%)	5	3/100 (3%)	5
Platelet count decreased	1/51 (2%)	1	3/55 (5.5%)	3	3/100 (3%)	3
Blood alkaline phosphatase increased	1/51 (2%)	1	2/55 (3.6%)	2	2/100 (2%)	2
Blood calcium decreased	1/51 (2%)	1	2/55 (3.6%)	2	2/100 (2%)	2
Blood potassium increased	1/51 (2%)	1	2/55 (3.6%)	2	2/100 (2%)	2
White blood cell count increased	0/51 (0%)	0	3/55 (5.5%)	4	3/100 (3%)	4
Blood urea increased	0/51 (0%)	0	2/55 (3.6%)	2	2/100 (2%)	2
Platelet count increased	0/51 (0%)	0	2/55 (3.6%)	2	2/100 (2%)	2
Metabolism and nutrition disorders
Hyperglycaemia	11/51 (21.6%)	14	4/55 (7.3%)	5	4/100 (4%)	5
Hyponatraemia	2/51 (3.9%)	2	3/55 (5.5%)	3	3/100 (3%)	3
Dyslipidaemia	1/51 (2%)	1	2/55 (3.6%)	2	2/100 (2%)	2
Renal and urinary disorders
Glycosuria	1/51 (2%)	1	3/55 (5.5%)	3	3/100 (3%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.