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)
- Conditions
- Raynauds phenomenon (RP)10003816
- Registration Number
- NL-OMON52928
- Lead Sponsor
- Gesynta Pharma AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
1. Subjects must provide signed and dated written informed consent before the
conduct of any study-specific procedures.
2. Male and female subjects aged 18-75 years inclusive.
3. SSc 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.
4. 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).
5. Women of childbearing potential (WOCBP) must be using a highly effective
method of contraception to avoid pregnancy throughout the study and for 4 weeks
after the last dose of IMP in such manner that the risk of pregnancy is
minimised. (Clinical Trials Facilitation Group, 2014).
6. Women must not be pregnant or breastfeeding.
7. 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.
8. Ability of subjects to participate fully in all aspects of this clinical
trial.
1. SSc disease duration of greater than 120 months from first non-Raynaud
manifestation
2. Current smokers or stopped smoking or used nicotine in any form <3 months
prior to Visit 1 .
3. Dose-change or initiation of vasodilating substances (calcium blockers or
PDE-5 inhibitors) within 4 weeks prior to Visit 1. Subjects are not allowed to
use a combination of calcium blockers and PDE-5 inhibitors from 4 weeks prior
to Visit 1 and throughout the study.
4. Use of iloprost or other intravenous (iv) or per os (po) prostacyclin
receptor agonist within 4 weeks prior to Visit 1.
5. 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 prior to Visit 1.
Note: Subjects could be included if they have been treated with a stable dose
of mycophenolic acid during 4 weeks prior to study entry.
6. Use of systemic corticosteroids within 4 weeks prior to visit 1 and during
the course of the study.
7. Use of moderate or strong CYP3A4 inhibitors within 5 terminal half-lives
or one week, whichever is longer, prior to Visit 2. Examples of a moderate or
strong CYP3A4 inhibitors are diltiazem, verapamil and grapefruit juice
8. 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.
9. Prolonged corrected QT interval by Friderica (QTcF) defined as a mean QTcF
>450 msec at Visit 1, or at Visit 2 (prior randomization).
10. Creatinine clearance <50 mL/min (determined by Cockcroft-Gault equation) at
Screening (Visit 1).
11. Active digital ulcer (DU) within 4 weeks prior to Visit 1.
12. Have known allergies to any components of the GS-248 formulation.
13. Clinically meaningful laboratory abnormalities at Screening (Visit 1), as
determined and documented by the Investigator.
14. Positive test results for HBsAg, HCVAb or HIV-1 and/or -2 antibodies at
Screening (Visit 1).
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).
16. Subject is mentally or legally incapacitated at the time of screening or
has a history of clinically significant psychiatric disorders that would impact
the subject*s ability to participate in the study according to the
Investigator.
17. Malignancy within the past 5 years except for in situ removal of basal cell
carcinoma and cervical intraepithelial neoplasia grade I.
18. Planned major surgery within the duration of the study.
19. Blood donation (or corresponding blood loss) within 12 weeks prior to Visit
1.
20. Participation in another interventional clinical study involving IMP within
4 weeks or given an experimental drug within 5 half-lives, whichever longest,
prior to Visit 1.
Exclusion Criterion for Cold Challenge
At Visit 2: Finger temperature below 27°C after acclimatising at an
ambient temperature of 23°C (±2°C) for a period of 20 minutes.
Randomization Criteria:
In addition to fulfilling all inclusion and exclusion criteria, subjects must
fulfil the following criteria to be randomised:
1. >=7 RP attacks during the last week of the run-in period as captu
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Efficacy:<br /><br>Mean change from baseline to week 4 in the number of Raynaud*s Phenomenon<br /><br>attacks per week.<br /><br><br /><br>Primary safety:<br /><br>• Incidence of Adverse events.<br /><br>• Incidence of Serious Adverse Events.<br /><br>• Clinical laboratory and vital signs.<br /><br><br /><br>Key secondary efficacy:<br /><br>• Mean change from baseline to week 4 in the Raynaud*s Condition Score (RCS).<br /><br>• Mean change from baseline to week 4 in the cumulative duration of Raynaud*s<br /><br>Phenomenon attacks.<br /><br>• Mean change from baseline to week 4 in pain experienced during RP attacks.<br /><br><br /><br>Exploratory efficacy:<br /><br>• Patient Global Impression of Change at week 4.<br /><br>• Physician Global Impression of Change at week 4.<br /><br>• Mean change in ASRAP Questionnaire score from baseline to week 4.</p><br>
- Secondary Outcome Measures
Name Time Method