A Study to Evaluate Guselkumab for the Treatment of Participants With New-onset or Relapsing Giant Cell Arteritis

Phase 2TerminatedNCT04633447

Janssen Research & Development, LLC53 enrolled

Overview

The primary purpose of this study is to evaluate the efficacy of guselkumab compared to placebo, in combination with a 26-week glucocorticoid (GC) taper regimen, in adult participants with new-onset or relapsing giant cell arteritis (GCA).

Giant cell arteritis (GCA) is a non-necrotizing granulomatous systemic vasculitis of unknown etiology affecting medium-sized and large arteries usually accompanied or preceded by systemic inflammation. Guselkumab is a monoclonal antibody (mAb) that binds to the p19 sub-unit of human interleukin (IL)-23 with high affinity and blocks binding of extracellular IL-23 to cell surface IL-23 receptor, inhibiting IL 23 specific intracellular signaling and subsequent activation and cytokine production. It is used in treatment of psoriatic arthritis, generalized pustular psoriasis, erythrodermic psoriasis. The study consists of a screening period (less than or equal to \[\<=\] 6 weeks), double-blind treatment period (48 weeks), and safety follow-up period (12 weeks). Participants who complete the Week 52 visit and are assessed to be in glucocorticoid (GC)-free remission, may have the option to participate in the long-term extension (LTE) period of the study for up to 12 months. This study will evaluate the efficacy, safety, Pharmacokinetics (PK), and immunogenicity of guselkumab in combination with a 26-week GC taper regimen for the treatment of active new-onset or relapsing GCA in adult participants. The total duration of the study is up to 66 weeks for the main study and for participants that continue in the LTE period, the total study duration will be up to 112 weeks.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Giant Cell Arteritis

Interventions

GuselkumabDRUG

Guselkumab will be administered subcutaneously.

PlaceboDRUG

Matching placebo will be administered subcutaneously.

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

Inclusion criteria * Diagnosis of Giant cell arteritis (GCA) according to the revised American College of Rheumatology criteria * GCA diagnosis confirmed by either temporal artery biopsy revealing features of GCA either at time of diagnosis or at other timepoint during disease history; or evidence of cranial GCA either at time of diagnosis or at other timepoint during disease history by cranial doppler-ultrasound; or cranial Magnetic Resonance Imaging (MRI) or Magnetic Resonance Angiography; or other imaging modality upon agreement with the sponsor or evidence of GCA by angiography or cross-sectional imaging (ultrasound, MRI, computed tomography \[CT\], positron emission tomography \[PET\]) * Have new onset or relapsing GCA * Have active GCA within 6 weeks of first study intervention: Active GCA: presence of signs and symptoms of GCA and elevated erythrocyte sedimentation rate (ESR) greater than or equal to (\>=) 30 millimeter per hour (mm/hour), or C-reactive protein (CRP) \>= 10 milligrams per liter (mg/L) (or 1 milligrams per deciliter \[mg/dL\]), attributed to active GCA. ESR \>= 30 mm/hour or CRP \>= 10 mg/L (or 1 mg/dL) is not required if active GCA has been confirmed by a positive temporal artery biopsy or ultrasound or other imaging modality within 6 weeks of first study intervention * Clinically stable GCA disease on a glucocorticoid (GC) dose between 20 and 60 milligrams per day (mg/day) (prednisone or equivalent) at randomization such that the participant is able to safely participate in the protocol defined prednisone taper regimen, in the opinion of the investigator Exclusion criteria * Has any known severe or uncontrolled GCA complications * Has any rheumatic disease other than GCA such that could interfere with assessment of GCA * Has a current diagnosis or signs or symptoms of severe, progressive, or concomitant medical condition that places the participant at risk by participating in this study) * Has or has had any major ischemic event, within 12 weeks of first study intervention. Has a personal history of arterial thrombosis or venous thromboembolism (including deep venous thrombosis \[DVT\] and Pulmonary Embolism \[PE\]) * Has any comorbidities requiring 3 or more courses of systemic GCs within 12 months of first study intervention, AND, inability, in the opinion of the investigator, to withdraw GC therapy through protocol-defined taper regimen due to suspected or established adrenal insufficiency, OR, currently on systemic chronic GC therapy for reasons other than GCA and be GC dependent and have the potential to flare due to GC tapering (e.g. unstable asthma, unstable COPD) * Has a history of, or ongoing, chronic or recurrent infectious disease * Has received within specified timeframe, or 5 half-lives (whichever is greater) , or has failed treatment with any investigational or approved biologic agents or Janus Kinase Inhibitor prior to first study intervention * Use of any of the following systemic immunosuppressant treatments within the specified timeframe prior to study start: Any cytotoxic agents (cyclophosphamide, chlorambucil, nitrogen mustard, or other alkylating agents) with 6 months; Hydroxychloroquine, cyclosporine A, azathioprine, tacrolimus, sirolimus, sulfasalazine, leflunomide with cholestyramine washout or mycophenolate mofetil/mycophenolic acid within 3 months; Intramuscular, intra-articular, intrabursal, epidural, intra-lesional or IV GCs within 6 week; and Methotrexate (MTX) within 12 weeks. If started MTX \>12 weeks prior to first study intervention MTX must have been at a stable dose for minimally 4 weeks and must not be receiving more than 25 mg oral or SC MTX per week * Has chronic continuous use of systemic GCs for greater than (\>) 4 years or inability, in the opinion of the investigator, to withdraw GC treatment through protocol-defined taper regimen due to suspected or established adrenal insufficiency

Locations (30)

Outcomes

Primary Outcomes

Main Study: Percentage of Participants Achieving Glucocorticoid (GC)-Free Remission at Week 28

GC free remission at Week 28 was defined as (1) no signs or symptoms of active Giant cell arteritis (GCA) at Week 28; (2) absence of GCA flare from first dose of the study drug through Week 28; and (3) adherence to the protocol specified 26-week GC taper regimen. GCA flare was defined as the recurrence of signs and symptoms of active GCA, with or without elevation of inflammatory markers, and with the necessity for an increase in GC dose for GCA.

Time frame: Week 28

Secondary Outcomes

Main Study: Percentage of Participants Achieving GC-Free Remission at Weeks 28, 32, 36, 40, 44, 48 and 52

GC free remission was defined as (1) no signs or symptoms of active GCA at Weeks 28, 32, 36, 40, 44, 48 and 52 respectively; (2) absence of GCA flare from first dose of the study drug through Weeks 28, 32, 36, 40, 44, 48 and 52; (3) adherence to the protocol specified 26-week GC taper regimen. GCA flare was defined as the recurrence of signs and symptoms of active GCA, with or without elevation of inflammatory markers, and with the necessity for an increase in GC dose for GCA.

Time frame: Weeks 28, 32, 36, 40, 44, 48 and 52

Main Study: Percentage of Participants Achieving Both GC-Free Remission and Normalization of Erythrocyte Sedimentation Rate (ESR) at Weeks 28, 32, 36, 40, 44, 48 and 52

GC-free remission at Weeks 28, 32, 36, 40, 44, 48 and 52 was defined as (1) no signs or symptoms of active GCA at Weeks 28, 32, 36, 40, 44, 48 and 52 respectively (2) absence of GCA flare from first dose of the study drug through Weeks 28, 32, 36, 40, 44, 48 and 52 (3) adherence to the protocol specified 26-week GC taper regimen. Normalization of ESR was defined as ESR less than (\<) 30 millimeter per hour (mm/hr) at Weeks 28, 32, 36, 40, 44, 48 and 52. GCA flare was defined as the recurrence of signs and symptoms of active GCA, with or without elevation of inflammatory markers, and with the necessity for an increase in GC dose for GCA.

Time frame: Weeks 28, 32, 36, 40, 44, 48 and 52

Data from ClinicalTrials.gov

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University of Kansas Medical Center

Kansas City, Kansas, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Cliniques Universitaires St-Luc

Brussels, Belgium

UZ Leuven Gasthuisberg

Leuven, Belgium

Mount Sinai Hospital

Toronto, Ontario, Canada

Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, Canada

CHU Dijon

Dijon, France

Hopital Cochin

Paris, France

Universitatsklinikum Erlangen

Erlangen, Germany

medius KLINIK KIRCHHEIM

Kirchheim unter Teck, Germany

...and 20 more locations

Main Study: Percentage of Participants Achieving Both GC-Free Remission and Normalization of C-Reactive Protein (CRP) at Weeks 28, 32, 36, 40, 44, 48 and 52

GC-free remission at Weeks 28, 32, 36, 40, 44, 48 and 52 was defined as (1) no signs or symptoms of active Giant cell arteritis (GCA) at Weeks 28, 32, 36, 40, 44, 48 and 52 respectively (2) absence of GCA flare from first dose of the study drug through Weeks 28, 32, 36, 40, 44, 48 and 52 (3) adherence to the protocol specified 26-week GC taper regimen. Normalization of CRP is defined as CRP \<10 milligrams per liter (mg/L) or \<1 milligrams per deciliter (mg/dL). GCA flare was defined as the recurrence of signs and symptoms of active GCA, with or without elevation of inflammatory markers, and with the necessity for an increase in GC dose for GCA.

Time frame: Weeks 28, 32, 36, 40, 44, 48 and 52

Main Study: Percentage of Participants Achieving Both GC-Free Remission and Normalization of Both ESR and CRP at Weeks 28, 32, 36, 40, 44, 48 and 52

GC-free remission at Weeks 28, 32, 36, 40, 44, 48 and 52 was defined as (1) no signs or symptoms of active GCA at Weeks 28, 32, 36, 40, 44, 48 and 52 respectively; (2) absence of GCA flare from first dose of the study drug through Weeks 28, 32, 36, 40, 44, 48 and 52; (3) adherence to the protocol specified 26-week GC taper regimen. Normalization of ESR is defined as ESR \< 30 mm/hr at Weeks 28, 32, 36, 40, 44, 48 and 52. Normalization of CRP is defined as CRP \<10 mg/L or \<1 mg/dL. GCA flare was defined as the recurrence of signs and symptoms of active GCA, with or without elevation of inflammatory markers, and with the necessity for an increase in GC dose for GCA.

Time frame: Weeks 28, 32, 36, 40, 44, 48 and 52

Main Study: Cumulative Glucocorticoid (GC) Dose

Total cumulative GC dose administered included GCA taper, GC rescue therapy as well as for all other indications (any oral GC) from baseline (Day 1) up to Weeks 28 and 52 was reported.

Time frame: Baseline (Day 1) up to Weeks 28 and 52

Main Study: Time to First GCA Disease Flare or Discontinuation of Study Intervention Due to Adverse Event (AE) of Worsening of GCA

Time to occurrence of GCA disease flare was defined as the time from first dose of the study agent to the occurrence of the first observation of GCA disease flare or discontinuation due to adverse event (AE) of worsening of GCA. GCA flare was defined as the recurrence of signs and symptoms of active GCA, with or without elevation of inflammatory markers, and with the necessity for an increase in GC dose for GCA.

Time frame: Baseline (Day 1) up to Week 30 and Week 52

Main Study: Number of Participants With GCA Disease Flares or Discontinuation of Study Intervention Due to AE of Worsening of GCA

Number of participants with GCA disease flares or discontinuation of study intervention due to AE of worsening of GCA were reported. GCA flare was defined as the recurrence of signs and symptoms of active GCA, with or without elevation of inflammatory markers, and with the necessity for an increase in GC dose for GCA.

Time frame: Baseline (Day 1) up to Week 30 and Week 52

Main Study: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Number of participants with TEAEs (including serious and non-serious AEs) were reported. An AE was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Any AE occurring at or after the initial administration of study intervention through the end of the main study was considered to be treatment emergent.