Cold Challenge With C21 in RP

• ClinicalTrials.gov Identifier: NCT04388176
• Recruitment Status: Completed
• First Posted: May 14, 2020
• Results First Posted: May 18, 2023
• Last Update Posted: May 18, 2023
• Sponsor: Vicore Pharma AB
• Collaborator: SGS Life Sciences, a division of SGS Belgium NV
• Information provided by (Responsible Party): Vicore Pharma AB

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Raynaud Phenomenon; Systemic Sclerosis	Drug: C21; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: This is a randomised, double-blind, placebo-controlled cold challenge study. A cross-over design is applied to control for inter-individual variability in response to cold challenge.
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: The study will be conducted in double-blind fashion and the allocation of treatments will not be disclosed until clean file has been declared and the database has been locked.
• Primary Purpose: Treatment
• Official 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)
• Actual Study Start Date: January 3, 2020
• Actual Primary Completion Date: December 14, 2020
• Actual Study Completion Date: December 14, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Other Outcome Measures:

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

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

United Kingdom

Department of Rheumatology, Salford Royal Hospital

Manchester, Salford, United Kingdom, M6 8HD

Sponsors and Collaborators

Vicore Pharma AB

SGS Life Sciences, a division of SGS Belgium NV

Investigators

• Principal Investigator: Ariane Herrick, MD; Department of Rheumatology Salford Royal Hospital, Manchester,United Kingdom

  Study Documents (Full-Text)

Documents provided by Vicore Pharma AB:

Study Protocol  [PDF] October 22, 2020

Statistical Analysis Plan  [PDF] February 1, 2021

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Vicore Pharma AB
• ClinicalTrials.gov Identifier: NCT04388176
• Other Study ID Numbers: VP-C21-004; 2019-003203-35 ( EudraCT Number )
• First Posted: May 14, 2020
• Results First Posted: May 18, 2023
• Last Update Posted: May 18, 2023
• Last Verified: July 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Vicore Pharma AB:

Systemic sclerosis; Raynaud's phenomenon; Vasoconstriction

Additional relevant MeSH terms:

Raynaud Disease; Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis; Pathologic Processes; Connective Tissue Diseases; Skin Diseases; Livedoid Vasculopathy; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Skin Diseases, Vascular; Compound 21; Anti-Inflammatory Agents