A Study to Investigate Safety of GS-248 and Efficacy on Raynauds' Phenomenon in Systemic Sclerosis

A Phase II, Randomized, Multi-center, Placebo-controlled, Double-blind Study to Investigate the Safety of GS-248, and Efficacy on Raynaud's Phenomenon (RP) and Peripheral Vascular Blood Flow, in Subjects With Systemic Sclerosis (SSc)

The primary objective of this study is to determine the safety, and evaluate the efficacy of GS-248 versus placebo on Raynaud's Phenomenon (RP) in subjects with Systemic Sclerosis (SSc).

Study Overview

• Status: Completed
• Conditions: Systemic Sclerosis
• Intervention / Treatment: Drug: GS-248; Drug: Placebo

Detailed Description

The primary objective of this study is to determine the safety, and evaluate the efficacy of GS-248 versus placebo on Raynaud's Phenomenon (RP) in subjects with Systemic Sclerosis (SSc).

This is a randomized, double-blind, placebo-controlled study conducted in multiple sites in 4 countries in Europe. Approximately 80 subjects will be randomized in a 1:1 allocation to receive either GS-248 (120 mg) or placebo once daily. The study will comprise an enrolment period, a treatment period, and a follow-up period, with a total of 5 study visits over approximately 10 weeks.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium
    • Investigator site
• Netherlands
  • Nijmegen, Netherlands
    • Investigator site
• Poland
  • Gdańsk, Poland
    • Investigator site
  • Kraków, Poland
    • Investigator site
  • Lublin, Poland
    • Investigator site
• United Kingdom
  • Bath, United Kingdom
    • Investigator site
  • Cambridge, United Kingdom
    • Investigator site
  • Dundee, United Kingdom
    • Investigator site
  • Leeds, United Kingdom
    • Investigator site
  • Liverpool, United Kingdom
    • Investigator site
  • London, United Kingdom
    • Investigator site
  • Manchester, United Kingdom
    • Investigator site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must provide signed and dated written informed consent before the conduct of any study-specific procedures.
• Male and female subjects aged 18-75 years inclusive.
• Systemic Sclerosis diagnosed according to European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria (van den Hoogen F et al. 2013). Subjects with signs of other autoimmune diseases (e.g. Sjögren's syndrome, myositis, rheumatoid arthritis) could be included if SSc is the dominating phenotype.
• Raynaud attacks typically ≥7 times per week during the last 4 weeks prior to screening despite background medication (only allowed vasodilatory therapy is calcium channel blockers or PDE-5 inhibitors).
• Women of childbearing potential must be using a highly effective method of contraception to avoid pregnancy throughout the study and for 4 weeks after the last dose of Investigational Medicinal Product in such manner that the risk of pregnancy is minimised.
• Women must not be pregnant or breastfeeding.
• Male subjects to agree to use condom in combination with use of contraceptive methods with a failure rate of <1% to prevent pregnancy and drug exposure of a partner, and refrain from donating sperm from the first date of dosing until 3 months after last dosing of the IMP.
• Ability of subjects to participate fully in all aspects of this clinical trial.

Exclusion Criteria:

• Systemic Sclerosis disease duration of greater than 120 months from first non-Raynaud manifestation
• Current smokers or stopped smoking <3 months prior to Visit 1.
• Dose-change or initiation of vasodilating substances (calcium blockers or PDE-5 inhibitors) within 4 weeks prior to Visit 1.
• Use of iloprost or other intravenous (iv) or po prostacyclin receptor agonist within 4 weeks prior to Visit 1.
• Ongoing treatment with immunosuppressive therapies (other than mycophenolate) including, but not restricted to; cyclophosphamide, azathioprine, methotrexate, or cyclosporine, or use of those medications within 4 weeks of trial entry.
• Use of systemic corticosteroids during 4 weeks before screening and during the course of the study.
• Concurrent serious medical condition, with special attention to cardiovascular conditions, which in the opinion of the Investigator makes the subject not suitable for this study.
• Prolonged QTcF interval defined as a mean QTcF >450 msec.
• Creatinine clearance <50 mL/min (determined by Cockcroft-Gault equation) at Screening.
• Active digital ulcer (DU) within 4 weeks prior to Visit 1.
• Clinically meaningful laboratory abnormalities at Screening (Visit 1), as determined and documented by the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: GS-248; GS-248, capsule, 120 mg, once daily for 4 weeks	Drug: GS-248; 120 mg, capsule, once daily for 4 weeks
PLACEBO_COMPARATOR: Placebo; placebo, capsule, once daily for 4 weeks	Drug: Placebo; capsule, once daily for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline to week 4 in the number of Raynaud attacks per week.	Patient reported number of Raynaud's attacks per day as registered in electronic diary.	Daily from Day -7 to Day 28
Mean change from baseline to week 4 in the Raynaud's Condition Score.	Patient reported Raynaud's Condition Score each day as registered in electronic diary.	Daily from Day -7 to Day 28
Mean change from baseline to week 4 in the cumulative duration of Raynaud attacks.	Patient reported duration of Raynaud's attacks per day as registered in electronic diary.	Daily from Day -7 to Day 28
Mean change from baseline to week 4 in pain experienced during Raynaud attacks.	Patient reported pain of each Raynaud attack using Numeric Rating Scale as registered in electronic diary.	Daily from Day -7 to Day 28
Number of treatment emergent adverse events	Frequency, severity and seriousness of treatment emergent adverse events	Daily from Day 1 to Day 42-49

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in peripheral blood flow in fingers	Peripheral blood flow will be measured with thermography assessments before and after cold challenge.	Day 1 at pre-dose and 2 hours post dose and Day 28 at pre dose

Collaborators and Investigators

• Sponsor: Gesynta Pharma AB
• Collaborators: Ergomed
• Investigators: Study Director: Charlotte Edenius, Gesynta Pharma

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 29, 2020
• Primary Completion (ACTUAL): June 15, 2022
• Study Completion (ACTUAL): June 15, 2022

Study Registration Dates

• First Submitted: January 28, 2021
• First Submitted That Met QC Criteria: February 5, 2021
• First Posted (ACTUAL): February 8, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Connective Tissue Diseases; Peripheral Vascular Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Raynaud Disease
• Other Study ID Numbers: GS-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No