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CompletedNCT04744207Updated Aug 9, 2024Results posted

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

A Phase 2 interventional study of GS-248 and Placebo in Systemic Sclerosis, sponsored by Gesynta Pharma AB. Completed at 12 sites in 4 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-08-09.

Sponsored by Gesynta Pharma AB · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
94
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Systemic Sclerosis
03

In context

Raynaud Disease

83 studies on the registry are indexed under Raynaud Disease; 8 are open to participants now.

This study's enrollment of 94 is above the median of 30 across 71 interventional studies indexed under Raynaud Disease.

Browse Raynaud Disease studies →

Lead sponsor

Gesynta Pharma AB is the lead sponsor of 4 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
94 participants (actual)

Study arms

  • Experimental
    GS-248

    GS-248, capsule, 120 mg, once daily for 4 weeks

    Drug: GS-248

  • Placebo comparator
    Placebo

    placebo, capsule, once daily for 4 weeks

    Drug: Placebo

Interventions

  • DrugGS-248

    120 mg, capsule, once daily for 4 weeks

  • DrugPlacebo

    capsule, once daily for 4 weeks

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively

Secondary outcomes

  1. Mean Change From Baseline to Week 4 in the Raynaud's Condition Score.

    Patients reported Raynaud's Condition Score (RCS) once a day in an electronic diary. RCS is a validated numeric rating scale (from 0 to 10) answering the question "What difficulty did you have today with your Raynaud's condition?" where a score of '0' = 'No difficulty', and a score of '10' = 'Extreme difficulty'.

    Time frame: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively

  2. Mean Change From Baseline to Week 4 in Pain Experienced During Raynaud Attacks.

    The patient reported the experienced pain of each Raynaud attack using a Numeric Rating Scale (NRS) from 0 to 10 in an electronic diary where '0'='No pain' and '10'='Worst imaginable pain'.

    Time frame: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively

  3. Mean Change From Baseline to Week 4 in the Mean Duration of Raynaud's Attacks

    The patient reported the start time (hh:mm) and stop time (hh:mm) of each Raynaud's attack in the electronic diary.

    Time frame: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively

  4. Mean Change From Baseline to Week 4 in the Cumulative Duration of Raynaud Attacks.

    The patient reported the start time (hh:mm) and stop time (hh:mm) of each Raynaud's attack in the electronic diary.

    Time frame: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively

07

Results

Posted Aug 9, 2024

Participant flow

In addition to fulfilling all eligibility criteria, subjects must fulfil the following criteria to be randomised: •≥7 RP attacks during the last week of the run-in period as captured in the eDiary, with no more than 2 days without RP attacks. •Compliance with the eDiary during the 7 most recent days prior to baseline (Visit 2), excluding the visit day itself, defined as having submitted ≥5 days of eDiary records (out of a possible 7 days) for RCS and RP during that period.

Treatment
Participant flow — Treatment
MilestoneGS-248Placebo
Started3336
Completed3034
Not completed32
Withdrew: Withdrawal by subject20
Withdrew: Adverse event12
Follow-up
Participant flow — Follow-up
MilestoneGS-248Placebo
Started3034
Completed3034
Not completed00

Outcome measures

PrimaryMean 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.

Time frame:
From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively
Reported as:
Least squares mean · number of attacks
Mean Change From Baseline to Week 4 in the Number of Raynaud Attacks Per Week.
number of attacksGS-248Placebo
Mean Change From Baseline to Week 4 in the Number of Raynaud Attacks Per Week.-3.41 (-5.83 to -0.99)-4.22 (-6.48 to -1.96)
Statistical analysis
  • GS-248 vs Placebo · ANCOVA · p = <0.05 · Least squares mean estimate: 0.81 · 95% CI -2.48 to 4.10
SecondaryMean Change From Baseline to Week 4 in the Raynaud's Condition Score.

Patients reported Raynaud's Condition Score (RCS) once a day in an electronic diary. RCS is a validated numeric rating scale (from 0 to 10) answering the question "What difficulty did you have today with your Raynaud's condition?" where a score of '0' = 'No difficulty', and a score of '10' = 'Extreme difficulty'.

Time frame:
From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively
Reported as:
Least squares mean · score
Mean Change From Baseline to Week 4 in the Raynaud's Condition Score.
scoreGS-248Placebo
Mean Change From Baseline to Week 4 in the Raynaud's Condition Score.-0.99 (-1.54 to -0.45)-0.95 (-1.45 to -0.46)
SecondaryMean Change From Baseline to Week 4 in Pain Experienced During Raynaud Attacks.

The patient reported the experienced pain of each Raynaud attack using a Numeric Rating Scale (NRS) from 0 to 10 in an electronic diary where '0'='No pain' and '10'='Worst imaginable pain'.

Time frame:
From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively
Reported as:
Least squares mean · numeric rating scale
Mean Change From Baseline to Week 4 in Pain Experienced During Raynaud Attacks.
numeric rating scaleGS-248Placebo
Mean Change From Baseline to Week 4 in Pain Experienced During Raynaud Attacks.-0.65 (-1.16 to -0.14)-0.60 (-1.07 to -0.13)
SecondaryMean Change From Baseline to Week 4 in the Mean Duration of Raynaud's Attacks

The patient reported the start time (hh:mm) and stop time (hh:mm) of each Raynaud's attack in the electronic diary.

Time frame:
From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively
Reported as:
Least squares mean · LN (minutes); back-transformed
Mean Change From Baseline to Week 4 in the Mean Duration of Raynaud's Attacks
LN (minutes); back-transformedGS-248Placebo
Mean Change From Baseline to Week 4 in the Mean Duration of Raynaud's Attacks1.06 (0.87 to 1.29)0.89 (0.74 to 1.08)
SecondaryMean Change From Baseline to Week 4 in the Cumulative Duration of Raynaud Attacks.

The patient reported the start time (hh:mm) and stop time (hh:mm) of each Raynaud's attack in the electronic diary.

Time frame:
From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively
Reported as:
Least squares mean · LN (minutes); back-transformed
Mean Change From Baseline to Week 4 in the Cumulative Duration of Raynaud Attacks.
LN (minutes); back-transformedGS-248Placebo
Mean Change From Baseline to Week 4 in the Cumulative Duration of Raynaud Attacks.0.70 (0.51 to 0.98)0.61 (0.45 to 0.82)

Adverse events

Collected over All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
GS-2480/33 (0%)0/33 (0%)10/33 (30.3%)
Placebo1/36 (2.8%)1/36 (2.8%)9/36 (25%)
Most frequent serious events
Most frequent serious events
EventGS-248Placebo
Thermal burnInjury, poisoning and procedural complications0/331/36
SepsisInfections and infestations0/331/36
Most frequent other events
Most frequent other events
EventGS-248Placebo
HeadacheNervous system disorders6/334/36
ArthralgiaMusculoskeletal and connective tissue disorders0/333/36
Abdominal pain upperGastrointestinal disorders2/330/36
NauseaGastrointestinal disorders2/331/36
White blood cell count decreasedInvestigations0/332/36

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)GS-248PlaceboTotal
<=18 years000
Between 18 and 65 years303262
>=65 years347
Age, Continuous
Age, Continuous(years)GS-248PlaceboTotal
Mean49.0 ± 10.650.6 ± 10.649.8 ± 10.5
Sex: Female, Male
Sex: Female, Male(Participants)GS-248PlaceboTotal
Female273360
Male639
Race (NIH/OMB)
Race (NIH/OMB)(Participants)GS-248PlaceboTotal
American Indian or Alaska Native000
Asian101
Native Hawaiian or Other Pacific Islander000
Black or African American000
White303464
More than one race000
Unknown or Not Reported224
Region of Enrollment
Region of Enrollment(participants)GS-248PlaceboTotal
Netherlands235
Belgium213
Poland172037
United Kingdom121224
Stratification factors FAS
Stratification factors FAS(Participants)GS-248PlaceboTotal
Ca-blockers181937
PDE-5 inhibitors91019
No treatment6713
08

Study locations

12 sites
  • Investigator site
    Gent, Belgium
  • Investigator Site
    Nijmegen, Netherlands
  • Investigator site
    Gdańsk, Poland
  • Investigator Site
    Kraków, Poland
  • Investigator site
    Lublin, Poland
  • Investigator site
    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
09

References and documents

Study documents

  • Study protocol · Dec 10, 2021
  • Statistical analysis plan · Jul 19, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 9, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04744207
Lead sponsor
Gesynta Pharma AB
Collaborators
Ergomed
Responsible party
Sponsor
First posted
Feb 8, 2021
Start date
Dec 29, 2020
Primary completion
Jun 15, 2022
Completion
Jun 15, 2022
Results posted
Aug 9, 2024
Last update
Aug 9, 2024

Study contacts

Charlotte Edenius
study director · Gesynta Pharma

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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