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Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT02899026
Other study ID # 205012
Secondary ID
Status Withdrawn
Phase Phase 3
First received September 8, 2016
Last updated November 16, 2017
Start date March 15, 2018
Est. completion date August 26, 2021

Study information

Verified date November 2017
Source GlaxoSmithKline
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Sirukumab is a human anti-IL-6 monoclonal antibody that selectively binds to the cytokine with high affinity that may have therapeutic benefit in the treatment of polymyalgia rheumatica (PMR) by interrupting multiple pathogenic pathways. Sirukumab inhibits IL-6-mediated signal transducer and activator of transcription 3 (STAT3) phosphorylation, resulting in the inhibition of the biological effect of IL-6. This study will evaluate the efficacy and safety of sirukumab to characterize the benefit-to-risk profile of sirukumab in the treatment of active PMR. The study will be conducted in 2 parts (Part A and Part B) and consists of the following phases: Screening phase, Part A: 52-week double-blind treatment phase, Part B: 52-week extension phase with no study drug administration and a 16-week follow-up phase if applicable.

Approximately 150 subjects with a diagnosis of PMR and active disease within 6 weeks of baseline will be randomized into Part A, the 52-week double-blind treatment phase, to receive one of two doses of sirukumab or placebo, each in addition to a pre-specified prednisone taper. The efficacy and safety of sirukumab in sustaining remission will be assessed at Week 52. Subjects completing Part A of the study who are in clinical remission will be eligible to enter Part B, the 52-week extension phase, designed to investigate the long-term maintenance of remission and safety following cessation of sirukumab treatment and to assess long-term corticosteroid use. Subjects will need to have follow-up safety evaluations for at least 16 weeks after receiving the last dose of study drug, applicable for those who have withdrawn prematurely from the study or who have completed Part A but are not eligible for Part B.


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Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Sirukumab
Sirukumab will be provided as 1 millilitre (mL) Pre-filled Syringe (PFS), containing 100 mg/mL or 50 mg/mL of sirukumab, fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug
Placebo to match sirukumab
Placebo to match sirukumab will be provided as 1.0 mL PFS fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug
Prednisone /Prednisone placebo
Prednisone will be provided as tablets with dosage level up to 20 mg/day. All subjects will receive 20 mg prednisone at Baseline (Randomization) and follow predefined taper regimen (6 weeks or 52 weeks) based on treatment assignment. Placebo to match prednisone will be provided as tablets

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
GlaxoSmithKline

Outcome

Type Measure Description Time frame Safety issue
Primary Proportion of subjects in sustained Sustained remission at Week 52 is defined as having achieved all of the following: Remission by Week 12; Absence of disease flare following remission at Week 12 through Week 52; Completion of the assigned prednisone taper protocol; No requirement for rescue therapy at any time through Week 52. One flare before Week 12 is permitted if it can be successfully treated with a 5 mg/day prednisone add-on taper regimen in addition to the predefined taper schedule providing all other sustained remission criteria are met. Week (wk) 52
Secondary Part A: Cumulative prednisone dose at Week 52 Cumulative prednisone dose at Week 52 (Part A) Week 52
Secondary Part A&B: Cumulative prednisone dose over time Cumulative prednisone dose over time Over 104 weeks
Secondary Part A&B: Proportion of subjects in sustained remission Subjects with sustained disease remission will be evaluated Week 12 to Week 52 (Part A) and to Week 104 (Part B)
Secondary Part A&B: Proportion of subjects in remission while on a daily prednisone dose of 5mg Subjects in remission while on a daily prednisone dose of 5mg will be evaluated Week 52 (Part A) and Week 76 (Part B)
Secondary Part B: Proportion of subjects in remission while off prednisone Proportion of subjects in remission while off prednisone at baseline of Part B and who remain off prednisone during the first 24 weeks of Part B Week 76 (Part B)
Secondary Part A&B: Time to first PMR disease flare Time to first PMR flare after remission 52 weeks (Part A) and 104 weeks (Part B)
Secondary Part A&B: Number of PMR disease flares per subject over time PMR disease flare over time 52 weeks (Part A) and 104 weeks (Part B)
Secondary Part A: Change in PMR-activity score (AS) Change in PMR-AS score from baseline to Week 12 and 52 Week 12 and 52
Secondary Part A: Proportion of subjects meeting PMR-AS remission criteria of <1.5 Subjects withng PMR-AS remission criteria of <1.5 Week 12 and 52
Secondary Part A&B: Incidence of adverse events (AEs) and Serious AEs (SAEs) All AEs and SAEs will be reported 52 weeks (Part A) and 104 weeks (Part B)
Secondary Part A: Incidence of GC-related AEs GC-related AEs will be reported 52 weeks
Secondary Part A&B: Vital sign assessment as measure of safety Vital sign assessment includes systolic and diastolic blood pressure, pulse rate and body temperature Baseline (Week 0) to Week 52 (Part A) and Week 104 (Part B)
Secondary Part A&B: Number of subjects having abnormal hematology parameters as a measure of safety Blood samples will be collected to measure hematological parameters such as platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, white blood cell (WBC) count (including neutrophil count, lymphocyte count, monocyte count, eosinophil count and basophils count). Baseline (Week 0) to Week 52 (Part A) and Week 104 (Part B)
Secondary Part A&B: Number of subjects having abnormal clinical chemistry parameters as a measure of safety Blood samples will be collected to measure serum chemistry parameters such as sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, glucose aspartate transaminase, alanine transaminase, alkaline phosphatase, calcium, phosphate, albumin, total protein, direct, indirect and total bilirubin Baseline (Week 0) to Week 52 (Part A) and Week 104 (Part B)
Secondary Part A&B: Assessment of quality of life using the 36-item Short Form Health Survey version 2 (SF-36v2) (acute) Patient report of quality of life 52 weeks (Part A) and 104 weeks (Part B)
Secondary Part A&B: Functional Assessment of Chronic Illness Therapy (FACIT )-Fatigue Patient report of elements of fatigue 52 weeks (Part A) and 104 weeks (Part B)
Secondary Part A&B: Assessment of pain Pain assessed by patient reported rating on a numeric rating scale from 0 to 10 52 weeks (Part A) and 104 weeks (Part B)
Secondary Part A&B: Assessment of steroid impact Patient assessment of the side effects and impact of steroids on PMR symptoms over time 52 weeks (Part A) and 104 weeks (Part B)
Secondary Part A&B: Modified Health Assessment Questionnaire (MHAQ) Patient reported outcome of disease-related disability, discomfort, and quality of life 52 weeks (Part A) and 104 weeks (Part B)
Secondary Part A&B: Assessment of Patient Global Impression of Change (PGIC) Estimate of the magnitude of patient response to treatment at different time points by patient report 52 weeks (Part A) and 104 weeks (Part B)
Secondary Part A&B: Patient Global Assessment of Disease Activity (PtGA) Patient report of PMR disease activity 52 weeks (Part A) and 104 weeks (Part B)
Secondary Part A&B: Duration of Morning Stiffness Patient report of the duration of morning stiffness 52 weeks (Part A) and 104 weeks (Part B)
Secondary Part A&B: Physician Global Assessment of Disease Activity (PhGA) Physician assessment of PMR disease activity on a scale of 0-100 52 weeks (Part A) and 104 weeks (Part B)
Secondary Part A&B: Pharmacokinetics: Serum concentrations of sirukumab Blood samples for Pharmacokinetic (PK) analysis of sirukumab serum concentrations will be collected at Baseline, wk 4, wk 8, wk 12, wk 16, wk 24, wk 36 and wk 52 in Part A; and at wk 60 and wk 68 (Part B) 68 weeks
Secondary Part A&B: Serum anti-sirukumab antibodies Blood samples for antibodies analysis of sirukumab will be collected at Baseline, wk 24 and wk 52 in Part A; and at wk 68 in Part B 68 weeks
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