Cold challenge with C21 in Raynaud's Phenomenon secondary to SSC
Research type
Research Study
Full title
A Phase 2, single-center, randomised, double-blind, placebo-controlled, cross-over, cold challenge study investigating the effect of C21 on cold-induced vasoconstriction in subjects with Raynaud’s Phenomenon (RP) secondary to systemic sclerosis (SSc)
IRAS ID
272640
Contact name
Mimi F. Flensburg
Contact email
Sponsor organisation
Vicore Pharma AB
Eudract number
2019-003203-35
Duration of Study in the UK
0 years, 6 months, 30 days
Research summary
Research Summary
This is a single centre study to evaluate the effect and safety of C21 (a synthetic molecule which selectively stimulates the angiotensin type 2 receptor (AT2R) on blood flow in the fingers of sufferers of Raynaud's phenomenon (RP) secondary to systemic sclerosis.Participants will be enrolled in a 2 period crossover design in which each participant will act as his/her own control.
Sixteen participants will be included and scheduled to receive either C21 or placebo orally in liquid form and in random order without either the participants or the research staff knowing which treatment is administered first or second.
The study duration is not expected to exceed 7 weeks (including all protocol allowed extensions to visit windows) for each participant and will require 4 clinic visits consisting of a screening visit (Visit 1), two treatment visits (Visits 2 and 3) and an end of trial visit (Visit 4).Participants will stay in the clinic for at least 4 hours following each treatment period and be monitored for safety. The effect of C21 will be assessed by comparing the pre and post treatment finger temperature and blood flow. A comparison of the time taken for the hands to re-warm after being exposed to cold water following treatment with C21 compared to after treatment with placebo will also be made.
Safety evaluations during the study will include clinical laboratory tests, historical review of any symptoms, physical examination, vital signs, electrocardiograms, urinalysis and pregnancy tests in women of childbearing potential.
Potential analyses of plasma for biomarkers related to endothelium and platelets may also be performed.
Summary of Results
Title: A Phase 2, single-center, randomised, double-blind, placebo-controlled, cross-over, cold challenge study investigating the effect of C21 on cold-induced vasoconstriction in subjects with Raynaud’s phenomenon (RP) secondary to systemic sclerosis (SSc)This trial was a randomised, double-blind, placebo-controlled, cross-over cold challenge trial in patients with Raynaud’s phenomenon secondary to systemis sclerosis evaluating the efficacy and safety of a single oral dose of 200 mg C21.
Raynaud’s phenomenon (RP) is an episodic, painful ischaemic event affecting primarily fingers and toes in response to cold exposure or to emotional stress, and it is a very common manifestation of systemic sclerosis (SSc).C21 is a small molecule, an angiotensin II type 2 receptor (AT2R) agonist, intended to be used for the prevention and treatment of RP in patients with SSc. Current oral therapies for RP have limited efficacy, and there is a high medical need for new therapeutic alternatives.
The purpose of the trial was to evaluate the effect and safety of a single dose C21 200 mg in patients with RP secondary to SSc.
The trial planned to enroll 16 patients with Raynaud’s phenomenon secondary to systemic sclerosis, however, as recruitment was challenging during the COVID-19 pandemic, enrolment was stopped prematurely when 12 patients were randomised (assigned to treatment). All 12 (100%) randomised patients completed the trial.
The trial involved the following 4 visits:
• Visit 1: Screening (eligibility for trial participation) • Visit 2: Administration of trial treatment (C21 or placebo) and cold challenge (immersion of both hands in cooled water for 15 minutes) (3-21 days after Visit 1) • Visit 3: Administration of trial treatment (C21 or placebo, opposite of Visit 2) and cold challenge (3-7 days after Visit 2) • Visit 4: End of trial (3-15 days after Visit 3 or after withdrawal from trial)
At Visit 2 and 3, thermographic images of fingers were obtained immediately before treatment, every 10 minutes after treatment, and every 10 seconds for 15 minutes after the cold challenge.
Summary of Results
A measure of rewarming of fingers after the cold challenge, mean area under the curve (AUC), was numerically higher after C21 treatment compared to placebo, however no statistically significant difference was observed between the treatment periods in the 15 min observation period.The skin temperature of the fingers 15 min after the cold challenge was statistically significant higher after treatment with C21 compared to after placebo suggesting that C21 increases blood flow in fibrotic tissue via vasodilation (dilation of blood vessels).
At the end of the 15 min observation period, the finger temperature was still rising and a plateau was not reached, suggesting that the experimental design did not capture the full effect of C21
C21 was well tolerated in patients with RP secondary to SSc when administered at an oral, single dose of 200 mg. No severe or serious adverse events (side effects) were reported, and no events were considered related to C21.
In conclusion, C21 was well tolerated in patients with RP secondary to SSc when administered at an oral, single dose of 200 mg. C21 shows effect on finger temperature recovery after a cold challenge, but the experimental design did not seem to capture the full effect of C21, probably due to a too short observation period.
REC name
East of England - Cambridge South Research Ethics Committee
REC reference
19/EE/0330
Date of REC Opinion
13 Dec 2019
REC opinion
Further Information Favourable Opinion