Cold Challenge With C21 in RP

NCT04388176 | Completed Phase 2 Results

• 2 other identifiers: VP-C21-0042019-003203-35
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Keywords

Systemic sclerosis; Raynaud's phenomenon; Vasoconstriction

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Maximum Skin Temperature After Rewarming (MAX)

  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)

  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 Outcomes (2)

• 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)

  Before cold challenge (at 40 min) and post-recovery (at 55 min)

Study Arms (2)

C21 followed by placebo

EXPERIMENTAL

Drug: C21; Drug: Placebo

Placebo followed by C21

EXPERIMENTAL

Drug: C21; Drug: Placebo

Interventions

C21 DRUG

C21 as first treatment

C21 followed by placebo

Placebo DRUG

Placebo as second treatment

C21 followed by placebo

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained before any trial related procedures are performed.
• Subjects diagnosed with SSc according to European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria
• Age 19-75 years inclusive
• 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.

You may not qualify if:

• Smoking (including E-cigarettes) or use of nicotine replacement therapy for three months prior to Visit 1 and during the trial.
• BMI \>30
• Mixed connective tissue disease or "overlap" (i.e. those who satisfy more than one set of ACR criteria for a rheumatic disease).
• 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
• Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma and cervical intraepithelial neoplasia grade I
• Planned major surgery within the duration of the study
• 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)
• Blood donation (or corresponding blood loss) within three months prior to Visit 1
• 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

Sponsors & Collaborators

• Vicore Pharma AB: lead
• SGS Life Sciences, a division of SGS Belgium NV: collaborator

Study Sites (1)

Department of Rheumatology, Salford Royal Hospital

Manchester, Salford, M6 8HD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35894657 DERIVED

MeSH Terms

Conditions

Raynaud Disease; Scleroderma, Systemic

Interventions

compound 21

Condition Hierarchy (Ancestors)

Livedoid Vasculopathy; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Connective Tissue Diseases

Results Point of Contact

• Title: Carl-Johan Dalsgaard
• Organization: Vicore Pharma AB

carl-johan.dalsgaard@vicorepharma.com

+46 70 975 98 63

Study Officials

• Ariane Herrick, MD

  Department of Rheumatology Salford Royal Hospital, Manchester,United Kingdom

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 11, 2020
• First Posted: May 14, 2020
• Study Start: January 3, 2020
• Primary Completion: December 14, 2020
• Study Completion: December 14, 2020
• Last Updated: May 18, 2023
• Results First Posted: May 18, 2023

Record last verified: 2022-07

Locations

GB (1)