Primary:To evaluate the safety and tolerability of repeat subcutaneous doses of GSK2330811 in participants with dcSSc.Secondary:PK. PD (serum levels of total and free OSM). Antibodies against GSK2330811.
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Adverse events. Effects on laboratory, ECG parameters and vital signs (blood
pressure, heart rate, temperature).
Secondary outcome
Plasma concentrations of GSK2330811 and derived PK parameters. Serum levels of
total and free OSM. Incidence of anti-GSK2330811 antibodies.
Additional exploratory endpoints are included to explore pharmacology and
effect on selected clinical endpoints and biomarkers of fibrosis, inflammation
and vasculopathy in blood and skin.
Background summary
Systemic sclerosis (SSc) is a rare autoimmune disease with high morbidity and
mortality. There are no approved disease-modifying therapies and it is an area
of high unmet medical need. GSK2330811 is a monoclonal antibody that binds and
neutralises Oncostatin M (OSM). The biological roles of OSM indicate that
blocking OSM signalling would be expected to inhibit the key pathologic
processes of SSc. This is a proof of mechanism study to evaluate the safety,
tolerability, pharmacokinetics and pharmacodynamics of repeat subcutaneous
doses of GSK2330811 in participants with diffuse cutaneous SSc (dcSSc).
Study objective
Primary:
To evaluate the safety and tolerability of repeat subcutaneous doses of
GSK2330811 in participants with dcSSc.
Secondary:
PK. PD (serum levels of total and free OSM). Antibodies against GSK2330811.
Study design
Double blind (sponsor open) placebo-controlled, parallel group study to
evaluate safety and tolerability of subcutaneous GSK2330811.
First study in patients.
Randomization 3:1 to GSK2330811 and placebo (every other week). Co-treatment
with e.g. micofenolate and low dose corticosteroids accepted (see question D4A
for more details).
Two sequential cohorts. Cohort 1 (performed in other countries) has evaluated
the safety and tolerability of a repeat-dose predicted to provide sub-maximal
inhibition of OSM (100 mg GSK2330811 per dose), leading to a dose escalation
decision. Cohort 2 (multi-country study incl. NL) will now evaluate a
repeat-dose predicted to provide maximal inhibition of OSM (300 mg GSK2330811
per dose) to test proof of mechanism.
An internal Data Review Committee has been responsible for determining
progression from cohort 1 to cohort 2 and the number of subjects for cohort 2.
Study duration up to 34 weeks. Screening up to 6 weeks, treatment period 12
weeks (6 doses in total of 3 injections per dose for cohort 2), follow-up 16
weeks.
24 to 40 subjects.
Intervention
Treatment with GSK2330811 or placebo.
Study burden and risks
Risk: Adverse events of GSK2330811.
Burden:
11 visits in 34 weeks.
Complete physical examination: all visits.
Blood tests: all visits, 500 mL in total.
Pregnancy test: all visits (urine or blood).
Skin biopsy: 2 visits.
ECG: 4 visits.
Questionnaires (2): 3 visits.
Lung function: 4 visits (hospital), weekly at home (during screening and
treatment period).
Optional blood sample (6 mL) for genetic research.
Van Asch van Wijckstraat 55H
Amersfoort 3811 LP
NL
Van Asch van Wijckstraat 55H
Amersfoort 3811 LP
NL
Listed location countries
Age
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-003417-95-NL |
| CCMO | NL66668.100.18 |
| Other | www.gsk-clinicalstudyregister.com, registratienummer 201247 |