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A multi-centre, randomized, double-blind (sponsor open), placebocontrolled, repeat-dose, proof of mechanism study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and explore efficacy of GSK2330811 in participants with diffuse cutaneous systemic sclerosis (study 201247)

Phase 2
Completed
Conditions
systemic sclerosis
10003816
Registration Number
NL-OMON49656
Lead Sponsor
GlaxoSmithKline
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Not specified
Target Recruitment
3
Inclusion Criteria

* Males and females *18 years of age.
* Documented systemic sclerosis with cutaneous involvement and a disease
duration of *60 months and an mRSS *10 and *35 at screening.
* Active disease. See protocol section 6.1, item 5 for details.
* An area of uninvolved or mildly thickened skin that would allow subcutaneous
injection on abdomen, thigh or upper arm and on the fore arm for skin biopsies.
See protocol section 6.1, item 6-7 for details.
* Treatment with mycophenolate mofetil (*3,000 mg/day) or mycophenolate sodium
(*1,440 mg/day), oral corticosteroids (*10 mg/day of prednisone or equivalent),
phosphodiesterase 5 inhibitors and endothelin receptor antagonists is
permitted. See protocol section 6.1, item 8-11 for details.
* Female participants of childbearing potential: see protocol section 6.1, item
12b for details.

Exclusion Criteria

* Limited cutaneous SSc subset.
* Rheumatic autoimmune disease other than dcSSc. See protocol section 6.2, item
2 for details.
* FVC *50% of predicted, or a diffusing capacity of the lung for carbon dioxide
(DLCO) (corrected for hemoglobin) *40% of predicted.
* Pulmonary arterial hypertension, clinically significant inflammatory myositis.
* SSc renal crisis within 6 months of first dosing of study medication.
* Significant co-morbidities. See protocol section 6.2, item 7-10 for details.
* Active infection or history of infections within 6 months of first dosing.
See protocol section 6.2, item 11 for details.
* Prior or concomitant therapy as mentioned in protocol section 6.2, item
17-27.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>Adverse events. Effects on laboratory, ECG parameters and vital signs (blood<br /><br>pressure, heart rate, temperature).</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>Plasma concentrations of GSK2330811 and derived PK parameters. Serum levels of<br /><br>total and free OSM. Incidence of anti-GSK2330811 antibodies.<br /><br><br /><br>Additional exploratory endpoints are included to explore pharmacology and<br /><br>effect on selected clinical endpoints and biomarkers of fibrosis, inflammation<br /><br>and vasculopathy in blood and skin.</p><br>
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