Clinical Trial: Efficacy and Safety Study of Sirukumab in Subjects With Polymyalgia Rheumatica

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Sirukumab in Subjects With Polymyalgia Rheumatica

Brief 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safety evaluations for at least 16 weeks after receiving the last dose of study drug, applicable for those who have withdrawn prematurely from the study or who have completed Part A but are not eligible for Part B.


Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome: Proportion of subjects in sustained [ Time Frame: Week (wk) 52 ]

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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Part A: Cumulative prednisone dose at Week 52 [ Time Frame: Week 52 ]
    Cumulative prednisone dose at Week 52 (Part A)
  • Part A&B: Cumulative prednisone dose over time [ Time Frame: Over 104 weeks ]
    Cumulative prednisone dose over time
  • Part A&B: Proportion of subjects in sustained remission [ Time Frame: Week 12 to Week 52 (Part A) and to Week 104 (Part B) ]
    Subjects with sustained disease remission will be evaluated
  • Part A&B: Proportion of subjects in remission while on a daily prednisone dose of 5mg [ Time Frame: Week 52 (Part A) and Week 76 (Part B) ]
    Subjects in remission while on a daily prednisone dose of 5mg will be evaluated
  • Part B: Proportion of subjects in remission while off prednisone [ Time Frame: Week 76 (Part B) ]
    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
  • Part A&B: Time to first PMR disease flare [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
    Time to first PMR flare after remission
  • Part A&B: Number of PMR disease flares per subject over time [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
    PMR disease flare over time
  • Part A: Change in PMR-activity score (AS) [ Time Frame: Week 12 and 52 ]
    Change in PMR-AS score from baseline to Week 12 and 52
  • Part A: Proportion of subjects meeting PMR-AS remission criteria of <1.5 [ Time Frame: Week 12 and 52 ]
    Subjects withng PMR-AS remission criteria of <1.5
  • Part A&B: Incidence of adverse events (AEs) and Serious AEs (SAEs) [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
    All AEs and SAEs will be reported
  • Part A: Incidence of GC-related AEs [ Time Frame: 52 weeks ]
    GC-related AEs will be reported
  • Part A&B: Vital sign assessment as measure of safety [ Time Frame: Baseline (Week 0) to Week 52 (Part A) and Week 104 (Part B) ]
    Vital sign assessment includes systolic and diastolic blood pressure, pulse rate and body temperature
  • Part A&B: Number of subjects having abnormal hematology parameters as a measure of safety [ Time Frame: Baseline (Week 0) to Week 52 (Part A) and Week 104 (Part B) ]
    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).
  • Part A&B: Number of subjects having abnormal clinical chemistry parameters as a measure of safety [ Time Frame: Baseline (Week 0) to Week 52 (Part A) and Week 104 (Part B) ]
    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
  • Part A&B: Assessment of quality of life using the 36-item Short Form Health Survey version 2 (SF-36v2) (acute) [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
    Patient report of quality of life
  • Part A&B: Functional Assessment of Chronic Illness Therapy (FACIT )-Fatigue [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
    Patient report of elements of fatigue
  • Part A&B: Assessment of pain [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
    Pain assessed by patient reported rating on a numeric rating scale from 0 to 10
  • Part A&B: Assessment of steroid impact [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
    Patient assessment of the side effects and impact of steroids on PMR symptoms over time
  • Part A&B: Modified Health Assessment Questionnaire (MHAQ) [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
    Patient reported outcome of disease-related disability, discomfort, and quality of life
  • Part A&B: Assessment of Patient Global Impression of Change (PGIC) [ Time Frame: 52

    Original Secondary Outcome:

    • Part A: Cumulative prednisone dose at Week 52 [ Time Frame: Week 52 ]
      Cumulative prednisone dose at Week 52 (Part A)
    • Part A&B: Cumulative prednisone dose over time [ Time Frame: Over 104 weeks ]
      Cumulative prednisone dose over time
    • Part A&B: Proportion of subjects in sustained remission [ Time Frame: Week 12 to Week 52 (Part A) and to Week 104 (Part B) ]
    • Part A&B: Proportion of subjects in remission while on a daily prednisone dose of <5mg [ Time Frame: Week 52 (Part A) and Week 76 (Part B) ]
    • Part B: Proportion of subjects in remission while off prednisone [ Time Frame: Week 76 (Part B) ]
      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
    • Part A&B: Time to first PMR disease flare [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
      Time to first PMR flare after remission
    • Part A&B: Number of PMR disease flares per subject over time [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
    • Part A: Change in PMR-activity score (AS) [ Time Frame: Week 12 and 52 ]
      Change in PMR-AS score from baseline to Week 12 and 52
    • Part A: Proportion of subjects meeting PMR-AS remission criteria of <1.5 [ Time Frame: Week 12 and 52 ]
    • Part A&B: Incidence of adverse events (AEs) and Serious AEs (SAEs) [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
    • Part A: Incidence of GC-related AEs [ Time Frame: 52 weeks ]
    • Part A&B: Vital sign assessment as measure of safety [ Time Frame: Baseline (Week 0) to Week 52 (Part A) and Week 104 (Part B) ]
      Vital sign assessment includes systolic and diastolic blood pressure, pulse rate and body temperature
    • Part A&B: Number of subjects having abnormal hematology parameters as a measure of safety [ Time Frame: Baseline (Week 0) to Week 52 (Part A) and Week 104 (Part B) ]
    • Part A&B: Number of subjects having abnormal clinical chemistry parameters as a measure of safety [ Time Frame: Baseline (Week 0) to Week 52 (Part A) and Week 104 (Part B) ]
    • Part A&B: Assessment of quality of life using the 36-item Short Form Health Survey version 2 (SF-36v2) (acute) [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
      Patient report of quality of life
    • Part A&B: Functional Assessment of Chronic Illness Therapy (FACIT )-Fatigue [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
      Patient report of elements of fatigue
    • Part A&B: Assessment of pain [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
      Pain assessed by patient reported rating on a numeric rating scale from 0 to 10
    • Part A&B: Assessment of steroid impact [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
      Patient assessment of the side effects and impact of steroids on PMR symptoms over time
    • Part A&B: Modified Health Assessment Questionnaire (MHAQ) [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
      Patient reported outcome of disease-related disability, discomfort, and quality of life
    • Part A&B: Assessment of Patient Global Impression of Change (PGIC) [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
      Estimate of the magnitude of patient response to treatment at different time points by patient report
    • Part A&B: Patient Global Assessment of Disease Activity (PtGA) [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
      Patient report of PMR disease activity
    • Part A&B: Duration of Morning Stiffness [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
      Patient report of the duration of morning stiffness
    • Part A&B: Physician Global Assessment of Disease Activity (PhGA) [ Time Frame: 52 weeks (Part A) and 104 weeks (Part B) ]
      Physician assessment of PMR disease activity on a scale of 0-100
    • Part A&B: Pharmacokinetics: Serum concentrations of sirukumab [ Time Frame: 68 weeks ]
      Blood samples for Pharmacokinetic (PK) analysis of sirukumab serum c

      Information By: GlaxoSmithKline

      Dates:
      Date Received: September 8, 2016
      Date Started: March 15, 2018
      Date Completion: August 26, 2021
      Last Updated: May 22, 2017
      Last Verified: May 2017