Trial Outcomes & Findings for Cold Challenge With C21 in RP (NCT NCT04388176)
NCT ID: NCT04388176
Last Updated: 2023-05-18
Results Overview
Area under the curve for rewarming of each finger after cold challenge as measured by thermography for 15 min
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
For 15 min after cold challenge (40-55 min after IMP [investigational manufacturing product] administration)
Results posted on
2023-05-18
Participant Flow
The trial planned to include 16 subjects, however as recruitment was challenging during the COVID-19 (coronavirus disease 2019) pandemic, enrolment was stopped prematurely when 12 subjects were randomised. This ensured that trial results could be available in a timely manner.
A total of 20 unique subjects provided informed consent and were enrolled in the trial. Seven of these were screening failures. In addition, 2 subjects were not randomised; 1 subject due to the COVID-19 pandemic and 1 subject due technical issues with the Holter ECG. The latter subject was re-screened. A total of 12 subjects were randomised.
Participant milestones
| Measure |
C21 Followed by Placebo
C21: C21 as first treatment
Placebo: Placebo as second treatment
|
Placebo Followed by C21
C21: C21 as second treatment
Placebo: Placebo as first treatment
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
|
Overall Study
COMPLETED
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Cold Challenge With C21 in RP
Baseline characteristics by cohort
| Measure |
C21 Followed by Placebo
n=6 Participants
C21: C21 as first treatment
Placebo: Placebo as second treatment
|
Placebo Followed by C21
n=6 Participants
C21: C21 as second treatment
Placebo: Placebo as first treatment
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Age, Continuous
|
59.5 years
n=5 Participants
|
51.5 years
n=7 Participants
|
55.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
6 participants
n=5 Participants
|
6 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Height
|
163.1 cm
n=5 Participants
|
164.3 cm
n=7 Participants
|
163.7 cm
n=5 Participants
|
|
Weight
|
68.3 kg
n=5 Participants
|
64.9 kg
n=7 Participants
|
66.6 kg
n=5 Participants
|
|
BMI
|
25.6 kg/m^2
n=5 Participants
|
24.2 kg/m^2
n=7 Participants
|
24.9 kg/m^2
n=5 Participants
|
PRIMARY outcome
Timeframe: For 15 min after cold challenge (40-55 min after IMP [investigational manufacturing product] administration)Population: Full analysis set
Area under the curve for rewarming of each finger after cold challenge as measured by thermography for 15 min
Outcome measures
| Measure |
Placebo
n=12 Participants
A single oral dose of placebo
|
C21 200 mg
n=12 Participants
A single oral dose of 200 mg C21
|
|---|---|---|
|
Area Under the Curve for Rewarming of Each Finger After Cold Challenge (AUC) as Measured by Thermography
|
19558.43 C*sec
Geometric Coefficient of Variation 4.36
|
20045.96 C*sec
Geometric Coefficient of Variation 7.68
|
SECONDARY outcome
Timeframe: For 15 min after cold challenge (40-55 min after IMP administration)Population: Full analysis set
Maximum skin temperature after rewarming within 15 min after cold challenge
Outcome measures
| Measure |
Placebo
n=12 Participants
A single oral dose of placebo
|
C21 200 mg
n=12 Participants
A single oral dose of 200 mg C21
|
|---|---|---|
|
Maximum Skin Temperature After Rewarming (MAX)
|
22.5043 °C
Geometric Coefficient of Variation 3.73
|
23.5336 °C
Geometric Coefficient of Variation 8.49
|
SECONDARY outcome
Timeframe: Baseline, 10, 20, 30 and 40 minPopulation: The full analysis set
The distal dorsal difference, defined as the difference in temperature between the dorsum and the finger (DDD), from administration of IMP until before cold challenge (0 to 40 min)
Outcome measures
| Measure |
Placebo
n=12 Participants
A single oral dose of placebo
|
C21 200 mg
n=12 Participants
A single oral dose of 200 mg C21
|
|---|---|---|
|
The Distal Dorsal Difference, Defined as the Difference in Temperature Between the Dorsum and the Finger (DDD)
Baseline
|
-2.810 °C
Standard Error 0.3375
|
-2.4215 °C
Standard Error 0.4950
|
|
The Distal Dorsal Difference, Defined as the Difference in Temperature Between the Dorsum and the Finger (DDD)
10 min
|
-3.2378 °C
Standard Error 0.3045
|
-3.395 °C
Standard Error 0.4580
|
|
The Distal Dorsal Difference, Defined as the Difference in Temperature Between the Dorsum and the Finger (DDD)
20 min
|
-3.0596 °C
Standard Error 0.2323
|
-3.1419 °C
Standard Error 0.4792
|
|
The Distal Dorsal Difference, Defined as the Difference in Temperature Between the Dorsum and the Finger (DDD)
30 min
|
-3.1005 °C
Standard Error 0.1903
|
-3.0347 °C
Standard Error 0.4037
|
|
The Distal Dorsal Difference, Defined as the Difference in Temperature Between the Dorsum and the Finger (DDD)
40 min
|
-2.7921 °C
Standard Error 0.1918
|
-2.9448 °C
Standard Error 0.333
|
SECONDARY outcome
Timeframe: 2 min after cold challenge (40-42 min after IMP administration)Population: The full analysis set
Outcome measures
| Measure |
Placebo
n=12 Participants
A single oral dose of placebo
|
C21 200 mg
n=12 Participants
A single oral dose of 200 mg C21
|
|---|---|---|
|
Gradient of Rewarming in the First 2 Minutes Post-cold Challenge (GRAD)
|
0.5412 °C/min
Geometric Coefficient of Variation 42.26
|
0.4482 °C/min
Geometric Coefficient of Variation 39.35
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From intake of IMP to start of cold challenge (0-40 min)Population: The full analysis set
Outcome measures
| Measure |
Placebo
n=12 Participants
A single oral dose of placebo
|
C21 200 mg
n=12 Participants
A single oral dose of 200 mg C21
|
|---|---|---|
|
Change in Finger Temperature From Intake of IMP to Start of Cold Challenge
|
-0.697 °C
Standard Error 0.471
|
-1.347 °C
Standard Error 0.343
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Before cold challenge (at 40 min) and post-recovery (at 55 min)Population: The full analysis set
Nailfold capillaroscopy mean velocity was measured as red blood cell velocity before cold challenge and post recovery
Outcome measures
| Measure |
Placebo
n=12 Participants
A single oral dose of placebo
|
C21 200 mg
n=12 Participants
A single oral dose of 200 mg C21
|
|---|---|---|
|
Nailfold Capillaroscopy (Including Red Blood Cell Velocity Measurements)
Baseline
|
0.122 mm/sec
Standard Error 0.042
|
0.369 mm/sec
Standard Error 0.193
|
|
Nailfold Capillaroscopy (Including Red Blood Cell Velocity Measurements)
Before cold
|
0.302 mm/sec
Standard Error 0.175
|
0.207 mm/sec
Standard Error 0.054
|
|
Nailfold Capillaroscopy (Including Red Blood Cell Velocity Measurements)
Post recovery
|
0.318 mm/sec
Standard Error 0.140
|
0.323 mm/sec
Standard Error 0.149
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
C21 200 mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=12 participants at risk
A single oral dose of placebo
|
C21 200 mg
n=12 participants at risk
A single oral dose of 200 mg C21
|
|---|---|---|
|
Vascular disorders
Flushing
|
8.3%
1/12 • Number of events 1 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
0.00%
0/12 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
|
Blood and lymphatic system disorders
Anaemia
|
8.3%
1/12 • Number of events 1 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
0.00%
0/12 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12 • Number of events 1 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
0.00%
0/12 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
|
Nervous system disorders
Headache
|
8.3%
1/12 • Number of events 1 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
0.00%
0/12 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
|
Nervous system disorders
Hypoaesthesia
|
8.3%
1/12 • Number of events 1 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
0.00%
0/12 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
|
Nervous system disorders
Tremor
|
0.00%
0/12 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
8.3%
1/12 • Number of events 1 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/12 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
8.3%
1/12 • Number of events 1 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/12 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
8.3%
1/12 • Number of events 1 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
|
Skin and subcutaneous tissue disorders
Skin tightness
|
0.00%
0/12 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
8.3%
1/12 • Number of events 1 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/12 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
8.3%
1/12 • Number of events 1 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/12 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
8.3%
1/12 • Number of events 1 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/12 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
16.7%
2/12 • Number of events 2 • From signing of informed consent through study completion, an average of 30 days
At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place