Phase 2 N=35 Randomized Triple-blind Treatment

Proof of Mechanism Study of GSK2330811 in Diffuse Cutaneous Systemic Sclerosis

Scleroderma, Systemic

Bottom Line

View on ClinicalTrials.gov: NCT03041025 ↗

Enrolled (actual)

Serious AEs

8.6%

Results posted

May 2021

Primary outcome: Primary: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) — 8; 3; 24; 1 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: GSK2330811 (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: GlaxoSmithKline
Primary completion: Jul 2020

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)	8; 3; 24; 1; 0; 2	—
PRIMARY Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count	-0.006; 0.013; 0.007; -0.005; -0.003; 0.003	—
PRIMARY Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC)	-2.8; 2.0; -0.2; -2.5; -0.7; -3.7	—
PRIMARY Change From Baseline in Hematology Parameter: Hematocrit	-0.0089; 0.0127; -0.0035; -0.0023; -0.0027; -0.0141	—
PRIMARY Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin (MCH)	-0.08; 0.03; 0.04; -0.24; 0.37; -0.23	—
PRIMARY Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV)	-0.63; 1.33; -0.39; 0.38; 0.33; -1.17	—
PRIMARY Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count	-0.05; 0.07; -0.01; -0.03; -0.07; -0.11	—
PRIMARY Change From Baseline in Hematology Parameter: Red Cell Distribution Width (RDW)	0.04; -0.27; -0.26; 0.24; -0.53; -0.47	—
PRIMARY Change From Baseline in Reticulocyte Production Index	0.2009; -0.1787; -0.2757; 0.0391; -0.2397; -0.2460	—
PRIMARY Change From Baseline Hematology Parameter: Reticulocytes	0.0026; -0.0053; -0.0037; 0.0001; -0.0040; -0.0030	—
PRIMARY Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	0; 0; 0; 8; 3; 23	—
PRIMARY Change From Baseline in Chemistry Parameter: Total Protein	1.0; 0.5; 0.4; -0.1; -1.0; 0.7	—
PRIMARY Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH)	-1.3; -1.0; 0.6; -2.3; 4.5; -1.1	—
PRIMARY Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin	0.571; 2.000; -0.957; -1.000; -3.000; -0.087	—
PRIMARY Change From Baseline in Chemistry Parameters: Cholesterol, Direct High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, Triglycerides	-0.125; 0.067; 0.450; -0.093; -0.033; -0.036	—
PRIMARY Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea	0.011; -0.020; -0.013; -0.035; -0.070; -0.036	—
PRIMARY Change From Baseline in Chemistry Parameter: Estimated Glomerular Filtration Rate	-6.4180; 1.7630; -0.7528; -4.3085; -2.7765; -1.5543	—
PRIMARY Number of Participants With Emergent Worst Case Urinalysis Results by Dipstick	0; 0; 0; 0; 0; 3	—
PRIMARY Number of Participants With Vital Signs Relative to Change From Baseline by Potential Clinical Importance (PCI) Criteria	2; 0; 2; 0; 0; 1	—
PRIMARY Change From Baseline in Body Temperature	0.037; 0.400; 0.117; 0.037; 0.467; 0.130	—
PRIMARY Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings	3; 2; 10; 0; 0; 1	—
SECONDARY Plasma Concentrations of GSK2330811	NA; 0.0; 5510.7; 16197.9; 7782.3; 23407.0	—
SECONDARY Concentration at the End of the Dosing Interval (Ctrough) of GSK2330811	10993.0; 29254.4	—
SECONDARY Apparent Clearance (CL/F) of GSK2330811	0.0147	—
SECONDARY Apparent Volume of Distribution (Vss/F) of GSK2330811	3.25	—
SECONDARY Serum Level of Total Oncostatin M (OSM)	22.110; 30.590; 27.455; 28.175; 576.850; 721.020	—
SECONDARY Serum Level of Free OSM	19.72; 28.93; 20.74; 23.85; 0.73; 0.73	—
SECONDARY Number of Participants With Positive Anti-GSK2330811 Antibodies	0; 0; 3; 0; 0; 1	—

Summary

GSK2330811 is a humanized monoclonal antibody which is in development for systemic sclerosis (SSc), a rare autoimmune disease with high morbidity and mortality. Currently, there are no approved disease modifying therapies and it is an area of high unmet medical need. GSK2330811 has been shown to bind and neutralize Oncostatin M (OSM) that has been associated with fibrosis, vasculopathy and inflammation in a number of diseases. This multi-center, randomized, double-blind (sponsor open), placebo controlled, proof of mechanism study will be the first study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of repeat subcutaneous (SC) doses of GSK2330811 in male and female participants with diffuse cutaneous SSc (dcSSc). Participants with active disease and a disease duration of <= 60 months will be enrolled. Approximately 24 to 40 participants will be randomized across two sequential cohorts. Cohort 1 will evaluate a repeat-dose predicted to provide sub-maximal inhibition of OSM, leading to a dose escalation decision. Cohort 1 is planned to consist of at least 4 participants, randomized such that 3 participants will receive GSK2330811 100 milligram (mg) and 1 will receive placebo. Cohort 2 is planned to consist of at least 20 participants, randomized such that participants will receive GSK2330811 300 mg and placebo in a 3:1 ratio respectively. The duration of the study is up to 34 weeks including a screening period of up to 6 weeks, treatment period of 12 weeks and follow-up period of 16 weeks.

Eligibility Criteria

Inclusion Criteria

Participants of 18 years or over, at the time of signing the informed consent.
Documented diagnosis of systemic sclerosis with diffuse cutaneous involvement.
Modified rodnan skin score (mRSS) >=10 and =6 mg/liter (L) (0.6 mg/deciliter [dL]), that in the opinion of the investigator is due to SSc.
Disease duration =3 mRSS units, compared with an assessment performed within the previous 6 months.
Involvement of one new body area and an increase of >=2 mRSS units compared with an assessment performed within the previous 6 months.
Involvement of two new body areas within the previous 6 months.
An area of uninvolved or mildly thickened skin that in the opinion of the investigator would allow subcutaneous injection either at abdomen, front or middle region of the thigh or at outer area of the upper arm.
An area of involved skin (mRSS >=1) on the forearm suitable for repeated skin biopsies to be collected.
Participants who are taking mycophenolate mofetil ( =3 months at the first dosing day (Day 1) and participant and investigator are willing to continue this dose until at least completion of the Day 85 (Week 12) visit. If mycophenolate was recently ceased, there must be >=3 months between the date mycophenolate was ceased and the first dosing day (Day 1).
Participants who are taking oral corticosteroids ( 2 times upper limit of normal (ULN) at screening.
Bilirubin >1.5 times ULN at screening (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin 480 milliseconds (msec) or QTc >500 msec in participants with bundle branch block at screening.
A history of carcinoma in situ and malignant disease, with the exception of basal cell carcinoma that has been completely excised prior to the study.
Treatment with methotrexate within 3 months prior to the first dosing day (Day 1).
Previous or planned bone marrow transplant (e.g. autologous stem cell transplant).
Treatment with a biologic within the following timeframes:
Tocilizumab, abatacept or anti- tumor necrosis factor (including etanercept, infliximab, certolizumab, golimumab or adalimumab) within 3 months prior to the first dosing day (Day 1).
Rituximab within 12 months prior to the first dosing day (Day 1).
For any other biologic consult the medical monitor.
Treatment with oral or intravenous cyclophosphamide within 6 months prior to the first dosing day (Day 1).
Treatment with any other non-biologic systemic immunosuppressive medication (e.g. azathioprine, tacrolimus, ciclosporin) not mentioned above within 4 weeks prior to the first dosing day (Day 1), with the exception of mycophenolate and permitted oral corticosteroid.
Treatment with topical immunosuppressive medications (e.g. topical corticosteroids, tacrolimus) within 1 week prior to the first dosing day (Day 1).
Treatment with intravenous prostanoids (e.g. iloprost) within 2 weeks prior to the first dosing day (Day 1) or planned treatment before the Day 85 (Week 12) visit.
Treatment with anti-fibrotic medications including tyrosine kinase inhibitors (e.g. nintedinib and imatinib) and pirfenidone within 3 months prior to the first dosing day (Day 1).
Live vaccine(s) within 4 weeks prior to the first dosing day (Day 1), or plans to receive such vaccines during the study.
Treatment with anti-coagulant medications, including warfarin, heparin, thrombin inhibitors, and factor Xa inhibitors within 2 weeks prior to the first dosing day (Day 1).
Treatment with anti-platelet medications (e.g. clopidogrel, prasugrel, ticagrelor and dipyridamole) within 2 weeks prior to first dosing day (Day 1). This does not include aspirin at doses of 150 mg or less, or non-steroidal anti-inflammatory drugs, which are permitted.
Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study treatment.
Exposure to more than 4 new chemical entities w

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03041025). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.