Cold Challenge With C21 in RP

Systemic Sclerosis Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04388176
• Other study ID #: VP-C21-004
• Secondary ID: 2019-003203-35
• Status: Completed
• Phase: Phase 2
• Start date: January 3, 2020
• Est. completion date: December 14, 2020

Study information

• Verified date: July 2022
• Source: Vicore Pharma AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 14, 2020
• Est. primary completion date: December 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Raynaud Disease
• Raynaud Phenomenon
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Drug:
• C21
C21 as first treatment
• C21
C21 as second treatment
• Placebo
Placebo as second treatment
• Placebo
Placebo as first treatment

Locations

Country	Name	City	State
United Kingdom	Department of Rheumatology, Salford Royal Hospital	Manchester	Salford

Sponsors (2)

Lead Sponsor	Collaborator
Vicore Pharma AB	SGS Life Sciences, a division of SGS Belgium NV

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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)
Primary	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	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)
Secondary	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
Secondary	Gradient of Rewarming in the First 2 Minutes Post-cold Challenge (GRAD)		2 min after cold challenge (40-42 min after IMP administration)