Cold Challenge With C21 in RP

NCT ID: NCT04388176

Last Updated: 2023-05-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-03
• Study Completion Date: 2020-12-14

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.

Conditions

Raynaud Phenomenon; Systemic Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

C21 followed by placebo

Group Type: EXPERIMENTAL

C21

Intervention Type: DRUG

C21 as first treatment

Placebo

Intervention Type: DRUG

Placebo as second treatment

Placebo followed by C21

Group Type: EXPERIMENTAL

C21

Intervention Type: DRUG

C21 as second treatment

Placebo

Intervention Type: DRUG

Placebo as first treatment

Interventions

C21

C21 as first treatment

Intervention Type: DRUG

C21

C21 as second treatment

Intervention Type: DRUG

Placebo

Placebo as second treatment

Intervention Type: DRUG

Placebo

Placebo as first treatment

Intervention Type: DRUG

Eligibility 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)

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SGS Life Sciences, a division of SGS Belgium NV

OTHER

Sponsor Role: collaborator

Vicore Pharma AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ariane Herrick, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Rheumatology Salford Royal Hospital, Manchester,United Kingdom

Locations

Department of Rheumatology, Salford Royal Hospital

Manchester, Salford, United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 35894657 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-003203-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VP-C21-004

Identifier Type: -

Identifier Source: org_study_id