Cold Challenge With C21 in RP

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 is a randomised, double-blind, placebo-controlled, cross-over phase 2 trial investigating the effect of C21 on cold-induced vasoconstriction in subjects with Raynaud's phenomenon secondary to systemic sclerosis. The purpose of the trial is to achieve a vasodilatory effect in subjects with Raynaud's phenomenon by stimulation of the AT2R (angiotensin II type 2 receptor) with C21.

Study Overview

• Status: Completed
• Conditions: Systemic Sclerosis; Raynaud Phenomenon
• Intervention / Treatment: Drug: C21; Drug: C21; Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Salford
    • Manchester, Salford, United Kingdom, M6 8HD
      • Department of Rheumatology, Salford Royal Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent must be obtained before any trial related procedures are performed.
2. Subjects diagnosed with SSc according to European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria
3. Age 19-75 years inclusive
4. RP secondary to SSc as determined by the investigator, and with a typical frequency of attacks during the winter months (November-March) of on average at least 5 per week.

Exclusion Criteria:

1. Smoking (including E-cigarettes) or use of nicotine replacement therapy for three months prior to Visit 1 and during the trial.
2. BMI >30
3. Mixed connective tissue disease or "overlap" (i.e. those who satisfy more than one set of ACR criteria for a rheumatic disease).
4. Concurrent serious medical condition with special attention to cardiac or ophthalmic conditions which in the opinion of the investigator makes the patient inappropriate for this study
5. Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma and cervical intraepithelial neoplasia grade I
6. Planned major surgery within the duration of the study
7. Subjects who forsake any alcohol intake or have known uncontrolled allergic conditions or allergy/hypersensitivity to any components of the trial drug or placebo excipients (see Section 7.1)
8. Blood donation (or corresponding blood loss) within three months prior to Visit 1

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

   • Any dose-change or initiation of vasoactive substances

     , and not able or willing to withhold these medications for 3 days preceding Visit 2 and Visit 3, respectively

   • Iloprost
   • Any treatment with CYP3A4 inducers (e.g. rifampicin, phenytoin, St John's Wort)
   • Any treatment with CYP3A4 inhibitors (e.g. clarithromycin, ketoconazole, nefazodone, itraconazole, ritonavir)
   • Any treatment with medicines that are substrates of CYP1A2, CYP3A4 or CYP2C9 with a narrow therapeutic range
   • Any experimental drug

   • Any systemic immunosuppressive therapy other than:

     • Inhaled corticosteroids which can be used throughout the trial period
     • The continuation of stable doses of <10 mg prednisolone
     • Mycophenolate mofetil (MMF) which must be withheld for 3 days preceding Visit 2 and Visit 3

10. Any of the following findings at the time of screening:

    • Finger temperature below 27°C after acclimatising at an ambient temperature of 23°C for a period of 20 minutes
    • Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG, as judged by the Investigator
    • Positive results for HBsAg, HCVAb or HIV 1+2 Ag/Ab
    • Positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG)
    • 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
11. Pregnant or breast-feeding female subjects.
12. Female subjects of childbearing potential not willing to use contraceptive methods described in Section 5.3.1.
13. Male subjects not willing to use contraceptive methods described in Section 5.3.1.
14. Participation in any other interventional trial during the trial period
15. Subjects known or suspected of not being able to comply with this trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: C21 followed by placebo	Drug: C21; C21 as first treatment; Drug: C21; C21 as second treatment; Drug: Placebo; Placebo as second treatment; Drug: Placebo; Placebo as first treatment
Experimental: Placebo followed by C21	Drug: C21; C21 as first treatment; Drug: C21; C21 as second treatment; Drug: Placebo; Placebo as second treatment; Drug: Placebo; Placebo as first treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve for Rewarming of Each Finger After Cold Challenge (AUC) as Measured by Thermography	Area under the curve for rewarming of each finger after cold challenge as measured by thermography for 15 min	For 15 min after cold challenge (40-55 min after IMP [investigational manufacturing product] administration)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Skin Temperature After Rewarming (MAX)	Maximum skin temperature after rewarming within 15 min after cold challenge	For 15 min after cold challenge (40-55 min after IMP administration)
The Distal Dorsal Difference, Defined as the Difference in Temperature Between the Dorsum and the Finger (DDD)	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)	Baseline, 10, 20, 30 and 40 min
Gradient of Rewarming in the First 2 Minutes Post-cold Challenge (GRAD)		2 min after cold challenge (40-42 min after IMP administration)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Finger Temperature From Intake of IMP to Start of Cold Challenge		From intake of IMP to start of cold challenge (0-40 min)
Nailfold Capillaroscopy (Including Red Blood Cell Velocity Measurements)	Nailfold capillaroscopy mean velocity was measured as red blood cell velocity before cold challenge and post recovery	Before cold challenge (at 40 min) and post-recovery (at 55 min)

Collaborators and Investigators

• Sponsor: Vicore Pharma AB
• Collaborators: SGS Life Sciences, a division of SGS Belgium NV
• Investigators: Principal Investigator: Ariane Herrick, MD, Department of Rheumatology Salford Royal Hospital, Manchester,United Kingdom

Publications and helpful links

General Publications

• Herrick AL, Batta R, Overbeck K, Raud J, Manning J, Murray A, Dinsdale G, Tornling G. A phase 2 trial investigating the effects of the angiotensin II type 2 receptor agonist C21 in systemic sclerosis-related Raynaud's. Rheumatology (Oxford). 2023 Feb 1;62(2):824-828. doi: 10.1093/rheumatology/keac426.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2020
• Primary Completion (Actual): December 14, 2020
• Study Completion (Actual): December 14, 2020

Study Registration Dates

• First Submitted: May 11, 2020
• First Submitted That Met QC Criteria: May 13, 2020
• First Posted (Actual): May 14, 2020

Study Record Updates

• Last Update Posted (Actual): May 18, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Systemic sclerosis; Vasoconstriction; Raynaud's phenomenon
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Connective Tissue Diseases; Peripheral Vascular Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Raynaud Disease; Anti-Inflammatory Agents; Compound 21
• Other Study ID Numbers: VP-C21-004; 2019-003203-35 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No