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Cold Challenge With C21 in RP

Primary Purpose

Raynaud Phenomenon, Systemic Sclerosis

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
C21
C21
Placebo
Placebo
Sponsored by
Vicore Pharma AB
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Raynaud Phenomenon focused on measuring Systemic sclerosis, Raynaud's phenomenon, Vasoconstriction

Eligibility Criteria

19 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Department of Rheumatology, Salford Royal Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

C21 followed by placebo

Placebo followed by C21

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Maximum Skin Temperature After Rewarming (MAX)
Maximum skin temperature after rewarming within 15 min after cold challenge
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)
Gradient of Rewarming in the First 2 Minutes Post-cold Challenge (GRAD)

Full Information

First Posted
May 11, 2020
Last Updated
July 21, 2022
Sponsor
Vicore Pharma AB
Collaborators
SGS Life Sciences, a division of SGS Belgium NV
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1. Study Identification

Unique Protocol Identification Number
NCT04388176
Brief Title
Cold Challenge With C21 in RP
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)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
January 3, 2020 (Actual)
Primary Completion Date
December 14, 2020 (Actual)
Study Completion Date
December 14, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vicore Pharma AB
Collaborators
SGS Life Sciences, a division of SGS Belgium NV

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Raynaud Phenomenon, Systemic Sclerosis
Keywords
Systemic sclerosis, Raynaud's phenomenon, Vasoconstriction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
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
ParticipantCare ProviderInvestigator
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.
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
C21 followed by placebo
Arm Type
Experimental
Arm Title
Placebo followed by C21
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
C21
Intervention Description
C21 as first treatment
Intervention Type
Drug
Intervention Name(s)
C21
Intervention Description
C21 as second treatment
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo as second treatment
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo as first treatment
Primary Outcome Measure Information:
Title
Area Under the Curve for Rewarming of Each Finger After Cold Challenge (AUC) as Measured by Thermography
Description
Area under the curve for rewarming of each finger after cold challenge as measured by thermography for 15 min
Time Frame
For 15 min after cold challenge (40-55 min after IMP [investigational manufacturing product] administration)
Secondary Outcome Measure Information:
Title
Maximum Skin Temperature After Rewarming (MAX)
Description
Maximum skin temperature after rewarming within 15 min after cold challenge
Time Frame
For 15 min after cold challenge (40-55 min after IMP administration)
Title
The Distal Dorsal Difference, Defined as the Difference in Temperature Between the Dorsum and the Finger (DDD)
Description
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)
Time Frame
Baseline, 10, 20, 30 and 40 min
Title
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 Pre-specified Outcome Measures:
Title
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)
Title
Nailfold Capillaroscopy (Including Red Blood Cell Velocity Measurements)
Description
Nailfold capillaroscopy mean velocity was measured as red blood cell velocity before cold challenge and post recovery
Time Frame
Before cold challenge (at 40 min) and post-recovery (at 55 min)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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 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 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 Pregnant or breast-feeding female subjects. Female subjects of childbearing potential not willing to use contraceptive methods described in Section 5.3.1. Male subjects not willing to use contraceptive methods described in Section 5.3.1. Participation in any other interventional trial during the trial period Subjects known or suspected of not being able to comply with this trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ariane Herrick, MD
Organizational Affiliation
Department of Rheumatology Salford Royal Hospital, Manchester,United Kingdom
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Rheumatology, Salford Royal Hospital
City
Manchester
State/Province
Salford
ZIP/Postal Code
M6 8HD
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
35894657
Citation
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.
Results Reference
derived

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Cold Challenge With C21 in RP

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