DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Efficacy and Safety Study of Sirukumab in Patients With Giant Cell Arteritis

Information source: GlaxoSmithKline
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Giant Cell Arteritis

Intervention: Sirukumab (Drug); Placebo to match sirukumab (Drug); Prednisone (Drug); Placebo to match prednisone (Drug)

Phase: Phase 3

Status: Not yet recruiting

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

Overall contact:
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com

Summary

Sirukumab is a fully human anti-interleukin-6 (IL-6) immunoglobulin G1-kappa with a high affinity and specificity for binding to the human IL-6 molecule that may have therapeutic benefit in the treatment of giant cell arteritis (GCA) by interruption of 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 GCA. The study will be conducted in 2 distinct parts (Part A and Part B) and consists of the following phases: Screening phase, Part A: 52-week double-blind treatment phase, Part B: 104-week extension phase with the option to receive open-label sirukumab based on disease status and a 16-week follow-up phase if applicable. Approximately 204 subjects with a diagnosis of GCA 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 will be eligible to enter Part B, the 104-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 with active GCA at the end of Part A or those with new onset of GCA flare during the first 52 weeks of Part B will be eligible to receive open-label sirukumab. Subjects will need to have follow-up safety evaluations for at least 16 weeks after receiving the last dose of study drug, applicable only for those who are withdrawn prematurely from the study or whose open-label sirukumab treatment in Part B completes after Week 88.

Clinical Details

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Sirukumab in the Treatment of Patients With Giant Cell Arteritis

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Proportion of subjects in sustained remission at Week 52 for sirukumab (100 mg every 2 weeks [q2w] for 12 months) as compared to placebo, each administered in addition to a 6-month prednisone treatment regimen

Secondary outcome:

Part A & B: Cumulative prednisone doses in subjects treated with sirukumab plus prednisone

Part A & B: Proportion of subjects in sustained remission

Part A & B: Measure of remission rates over time

Part A & B: Time to first GCA flare

Part A & B: Number of disease flares per subject over time

Part A & B: Safety: Incidence of adverse events

Part A & B: Safety: Incidence of corticosteroid-related adverse events

Part A & B: Composite of vital signs assessment as a measure of safety: blood pressure, pulse rate and temperature

Part A & B: Composite of clinical laboratory tests assessment as a measure of safety: clinical chemistry and hematology

Part A: Assessment of Patient Global Impression of Change (PGIC)

Part A & B: Pain assessment

Part A & B: Health Assessment Questionnaire-Disability Index (HAQ-DI)

Part A & B: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)

Part A & B: Assessment of steroid impact

Part A & B: Assessment of quality of life using the 36-item Short Form Version 2 Acute (SF-36v2 Acute)

Part A & B: Assessment of health status using the EuroQoL-5D (EQ-5D)

Part A: Pharmacodynamics: Change from baseline in erythrocyte sedimentation rate (ESR) over time

Part A: Pharmacodynamics: Change from baseline in serum C-reactive protein (CRP) over time

Part A: Pharmacokinetics: Serum concentrations of sirukumab

Part A & B: Immunogenicity: Serum anti-sirukumab antibodies

Eligibility

Minimum age: 50 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnosis of GCA defined by the following Revised GCA Diagnosis Criteria:

Age >=50 years. History of ESR >=50 millimeter/hour (mm/hour) or CRP >=2. 45 milligram/deciliter(mg/dL). Presence of at least one of the following: Unequivocal cranial symptoms of GCA; Unequivocal symptoms of polymyalgia rheumatic (PMR). Presence of at least one of the following: Temporal artery biopsy revealing features of GCA; Evidence of large-vessel vasculitis by angiography or cross-sectional imaging.

- Active GCA within 6 weeks of Randomization (Baseline) where active disease is defined

by an ESR >=30 mm/hr or CRP >=1 mg/dL AND the presence of at least one of the following: Unequivocal cranial symptoms of GCA; Unequivocal symptoms of PMR; Other features judged by the clinician investigator to be consistent with GCA or PMR flares.

- At screening, receiving or able to receive prednisone 20-60 mg/day for the treatment

of active GCA.

- Clinically stable GCA disease at baseline such that the subject is able to safely

participate in the blinded prednisone taper regimen in the opinion of the investigator.

- Practicing acceptable methods of birth control if a female of child-bearing

potential.

- No evidence of active or latent infection with Mycobacterium tuberculosis (TB).

Exclusion Criteria:

- Are pregnant or breastfeeding.

- Recent (within the past 12 weeks) or planned major surgery that would impact on study

procedures or assessments.

- Organ transplantation recipients (except corneas within 3 months prior to baseline

visit).

- Had prior treatment with any of the following:

Systemic immunosuppressives) within 4 weeks of baseline; Biologic agents targeted at reducing tumor necrosis factor-alpha (TNF-alpha) within 2-8 weeks of baseline, depending on the agent; Any prior use of tocilizumab or other anti-IL-6 agents; B-cell depleting agents (eg, rituximab) within 12 months prior to baseline or longer if B cell counts have not returned to normal range or baseline levels; Cytotoxic drugs such as cyclophosphamide, chlorambucil, nitrogen mustard, or other alkylating agents within 4 weeks of baseline; Abatacept within 8 weeks of baseline; Tofacitinib within 4 weeks of baseline; Methotrexate use within 2 weeks of baseline. Methylprednisolone > 100 mg/day intravenous (IV) (or equivalent) within 8 weeks of baseline.

- History of severe allergic reactions to monoclonal antibodies, human proteins, or

excipients.

- Evidence of serious concomitant disease, which in the opinion of the investigator

makes them unsuitable for participation in the study.

- Major ischemic event, unrelated to GCA, within 12 weeks of screening.

- Marked baseline prolongation of corrected QT (QTc) interval >= 450 milliseconds

(msec) (QTc by Bazett's formula [QTcB ]or QTc by Fridericia's formula [QTcF] ), history of Torsade de Pointes, family history of long QT syndrome, history of second or third degree heart block.

- Current liver disease that could interfere with the trial

- History of or current active diverticulitis, inflammatory bowel disease, or other

symptomatic gastrointestinal tract condition that might predispose to bowel perforation.

- History of known demyelinating diseases such as multiple sclerosis or optic neuritis.

- Active infections, or history of recurrent infections or have required management of

acute or chronic infections, as follows: Currently on any suppressive therapy for a chronic infection, history or suspicion of chronic infection, hospitalization for treatment of infection within 60 days of the baseline visit, or use of parenteral (IV) or intra-muscular [IM]) antimicrobials within 60 days of baseline or oral antimicrobials within 30 days of baseline

- Primary or secondary immunodeficiency or any other autoimmune disease.

- Human immunodeficiency virus (HIV) infection, hepatitis C or hepatitis B infection

- Live virus or bacterial vaccination within 3 months before the first administration

of study drug

Locations and Contacts

US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com

Additional Information

Starting date: September 2015
Last updated: August 20, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017