Clinical trial NCT04744207: A Study to Investigate Safety of GS-248 and Efficacy on Raynauds' Phenomenon in Systemic Sclerosis
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Sclerosis
Lead sponsor: Gesynta Pharma AB
Sponsor class: INDUSTRY
Collaborators: name: Ergomed
First posted: 2021-02-08
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Change From Baseline to Week 4 in the Number of Raynaud Attacks Per Week.
timeFrame: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively
Secondary outcomes:
measure: Mean Change From Baseline to Week 4 in the Raynaud's Condition Score.
timeFrame: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively
measure: Mean Change From Baseline to Week 4 in Pain Experienced During Raynaud Attacks.
timeFrame: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively
measure: Mean Change From Baseline to Week 4 in the Mean Duration of Raynaud's Attacks
timeFrame: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively
measure: Mean Change From Baseline to Week 4 in the Cumulative Duration of Raynaud Attacks.
timeFrame: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: Investigator site
city: Nijmegen
country: Netherlands
facility: Investigator Site
city: Gdańsk
country: Poland
facility: Investigator site
city: Kraków
country: Poland
facility: Investigator Site
city: Lublin
country: Poland
facility: Investigator site
city: Bath
country: United Kingdom
facility: Investigator site
city: Cambridge
country: United Kingdom
facility: Investigator site
city: Dundee
country: United Kingdom
facility: Investigator Site
city: Leeds
country: United Kingdom
facility: Investigator site
city: Liverpool
country: United Kingdom
facility: Investigator Site
city: London
country: United Kingdom
facility: Investigator Site
city: Manchester
country: United Kingdom
facility: Investigator site
Study officials:
affiliation: Gesynta Pharma
name: Charlotte Edenius
role: STUDY_DIRECTOR
References: