COVID-19
Conditions
Keywords
COVID-19
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.
Interventions
DRUGC21
C21
DRUGPlacebo
Placebo
Sponsors
Orphan Reach Ltd.
Vicore Pharma AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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) 6. 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 7. 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 8. Malignancy within the past 3 years with the exception of in situ removal of basal cell carcinoma and cervical intraepithelial neoplasia grade I 9. Treatment with any of the medications listed below within 1 week prior to Visit 1: 1. Strong Cytochrome p450 (CYP) 3A4 inducers (e.g. rifampicin, phenytoin, St. John's Wort, phenobarbital, rifabutin, carbamazepine, anti HIV drugs, barbiturates) 2. Warfarin 10. Pregnant or breast-feeding female subjects 11. Female subjects of childbearing potential not willing to use contraceptive methods as described in Section 5.3.1 12. Male subjects not willing to use contraceptive methods as described in Section 5.3.1 13. Subjects known or suspected of not being able to comply with this trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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. |
| 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 |
| 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. |
| 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 |
| 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 |
| 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 |
| 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) |
| 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. |
| 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 |
Countries
India, United Kingdom
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| C21 Treatment Oral C21 treatment 100 mg twice daily for 7 days | 51 |
| Placebo Treatment Oral placebo treatment twice daily for 7 days | 55 |
| Total | 106 |
Baseline characteristics
| Characteristic | Placebo Treatment | C21 Treatment | Total |
|---|---|---|---|
| Age, Continuous | 51.1 years | 54.3 years | 52.6 years |
| Body mass index | 25.1 kg/m^2 | 25.4 kg/m^2 | 25.2 kg/m^2 |
| CRP value ≤ median | 22 Participants | 24 Participants | 46 Participants |
| CRP value > median | 25 Participants | 21 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants | 51 Participants | 106 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 166.0 cm | 166.1 cm | 166.1 cm |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 55 Participants | 51 Participants | 106 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment India | 55 participants | 51 participants | 106 participants |
| Sex: Female, Male Female | 13 Participants | 13 Participants | 26 Participants |
| Sex: Female, Male Male | 42 Participants | 38 Participants | 80 Participants |
| Supplemental oxygen use at baseline | 32 Participants | 29 Participants | 61 Participants |
| Weight | 69.2 kg | 70.1 kg | 69.6 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 51 | 3 / 55 | 2 / 100 |
| other Total, other adverse events | 30 / 51 | 36 / 55 | 0 / 100 |
| serious Total, serious adverse events | 1 / 51 | 3 / 55 | 2 / 100 |
Outcome results
Primary
Change From Baseline in C-reactive Protein (CRP) After Treatment With C21 200 mg Daily Dose (100 mg b.i.d.)
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)
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| C21 Treatment | Change From Baseline in C-reactive Protein (CRP) After Treatment With C21 200 mg Daily Dose (100 mg b.i.d.) | 0.19 mg/L |
| Placebo Treatment | Change From Baseline in C-reactive Protein (CRP) After Treatment With C21 200 mg Daily Dose (100 mg b.i.d.) | 0.22 mg/L |
p-value: =0.4891ANCOVA
Comparison: 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.p-value: =0.0881ANCOVA
Secondary
Adverse Events
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)
Population: Safety analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| C21 Treatment | Adverse Events | 31 Participants |
| Placebo Treatment | Adverse Events | 37 Participants |
Secondary
Change From Baseline in Body Temperature
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)
Population: Subjects with measurements were included in the analysis for the full analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| C21 Treatment | Change From Baseline in Body Temperature | -0.11 °C |
| Placebo Treatment | Change From Baseline in Body Temperature | -0.34 °C |
p-value: =0.0492ANCOVA
Secondary
Change From Baseline in CA125
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)
Population: Subjects with measurements were included in the analysis for the full analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| C21 Treatment | Change From Baseline in CA125 | 1.16 u/mL |
| Placebo Treatment | Change From Baseline in CA125 | 1.17 u/mL |
p-value: =0.9418ANCOVA
Secondary
Change From Baseline in Ferritin
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)
Population: Subjects with measurements were included in the analysis for the full analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| C21 Treatment | Change From Baseline in Ferritin | 0.75 ng/mL |
| Placebo Treatment | Change From Baseline in Ferritin | 0.74 ng/mL |
p-value: =0.9733ANCOVA
Secondary
Change From Baseline in IL-10
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)
Population: Subjects with measurements were included in the analysis for the full analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| C21 Treatment | Change From Baseline in IL-10 | 0.66 pg/mL |
| Placebo Treatment | Change From Baseline in IL-10 | 0.73 pg/mL |
p-value: =0.5355ANCOVA
Secondary
Change From Baseline in IL-6
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)
Population: Subjects with measurements were included in the analysis for the full analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| C21 Treatment | Change From Baseline in IL-6 | 0.73 pg/mL |
| Placebo Treatment | Change From Baseline in IL-6 | 0.73 pg/mL |
p-value: =0.9923ANCOVA
Secondary
Change From Baseline in TNF
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)
Population: Subjects with measurements were included in the analysis for the full analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| C21 Treatment | Change From Baseline in TNF | 0.91 pg/mL |
| Placebo Treatment | Change From Baseline in TNF | 1.01 pg/mL |
p-value: =0.4738ANCOVA
Secondary
Number of Subjects Not in Need of Mechanical Invasive or Non-invasive Ventilation
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)
Population: Full analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| C21 Treatment | Number of Subjects Not in Need of Mechanical Invasive or Non-invasive Ventilation | 50 Participants |
| Placebo Treatment | Number of Subjects Not in Need of Mechanical Invasive or Non-invasive Ventilation | 53 Participants |
p-value: =0.6088Regression, Logistic
Secondary
Number of Subjects Not in Need of Oxygen Supply
Number of subjects not in need of oxygen supply at the end of treatment
Time frame: End-of treatment, Day 7 or 8
Population: Full analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| C21 Treatment | Number of Subjects Not in Need of Oxygen Supply | 37 Participants |
| Placebo Treatment | Number of Subjects Not in Need of Oxygen Supply | 30 Participants |
p-value: =0.0568Regression, Logistic
Secondary
Time on Oxygen Supply (for Those Not Needing Mechanical Invasive or Non-invasive Ventilation)
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)
Population: Full analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| C21 Treatment | Time on Oxygen Supply (for Those Not Needing Mechanical Invasive or Non-invasive Ventilation) | 5.0 days |
| Placebo Treatment | Time on Oxygen Supply (for Those Not Needing Mechanical Invasive or Non-invasive Ventilation) | 5.0 days |
p-value: =0.8588Wilcoxon (Mann-Whitney)
Secondary
Time to Need of Mechanical Invasive or Non-invasive Ventilation
Time to need of mechanical invasive or non-invasive ventilation during treatment period
Time frame: Treatment period of 7 days
Population: Subjects with measurements were included in the analysis for the full analysis set.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| C21 Treatment | Time to Need of Mechanical Invasive or Non-invasive Ventilation | 60.0 hours |
| Placebo Treatment | Time to Need of Mechanical Invasive or Non-invasive Ventilation | 77.925 hours |
p-value: =0.5757Log Rank
Post Hoc
Oxygen Supplementation at Day 14
Number of subjects requiring oxygen supplementation at Day 14
Time frame: Follow-up Day 14 (7 days after end-of-treatment)
Population: Full analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| C21 Treatment | Oxygen Supplementation at Day 14 | 1 Participants |
| Placebo Treatment | Oxygen Supplementation at Day 14 | 11 Participants |
p-value: =0.003Chi-squared