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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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A Phase 2, Multicenter, Randomized, Placebo-controlled, Double-blind, Proof-of-Concept Study to Evaluate Guselkumab for the Treatment of Participants With New-onset or Relapsing Giant Cell Arteritis

Conditions
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Giant Cell Arteritis

Intervention / Treatment
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* Drug: Guselkumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Guselkumab<br>Participants will receive guselkumab subcutaneously (SC) every 4 weeks from Week 0 through Wweek 48. This will be in combination with a protocol specified 26-week GC taper. Participants of the long-term extension (LTE) period will continue to receive subcutaneous (SC) injections every 4 weeks starting at Week 52 (LTE Week 0) through Week 100 (LTE Week 48) or until the participants have a Giant cell arteritis (GCA) flare, or the participants discontinues treatment due to unblinding after the Week 60 DBL for the Main study, or until a decision is made not to continue clinical development in this GCA population, whichever occurs first. | Drug: Guselkumab<br>* Guselkumab will be administered subcutaneously.<br>* Other names: CNTO 1959;|
| Experimental: Placebo<br>Participants will receive matching placebo SC every 4 weeks from Week 0 through Week 48. This will be in combination with a protocol-specified 26-week GC taper. Participants of the LTE period will continue to receive SC injections every 4 weeks starting at Week 52 (LTE Week 0) through Week 100 (LTE Week 48) or until the participants have a GCA flare, or the participants discontinues treatment due to unblinding after the Week 60 DBL for the Main study, or until a decision is made not to continue clinical development in this GCA population, whichever occurs first. | Drug: Placebo<br>* Matching placebo will be administered subcutaneously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Glucocorticoid (GC)-Free Remission | Percentage of participants achieving GC-free remission will be assessed. | At Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving GC-Free Remission | Percentage of participants achieving GC-free remission will be assessed. | From Week 28 up to Week 52 | 
| Percentage of Participants Achieving GC-Free Remission and Normalization of Erythrocyte Sedimentation Rate (ESR) | Percentage of participants achieving GC-free remission and normalization of ESR will be assessed using the Westergren method. | At Week 28 and up to Week 52 | 
| Percentage of Participants Achieving GC-Free Remission and Normalization of C-Reactive Protein (CRP) | Percentage of participants achieving GC-free remission and normalization of CRP will be assessed. | At Week 28 and up to Week 52 | 
| Percentage of Participants Achieving GC-Free Remission and Normalization of Both ESR and CRP | Percentage of participants achieving normalization of both ESR and CRP will be assessed. | At Week 28 and up to Week 52 | 
| Cumulative GC dose | Cumulative GC dose will be assessed. | Through Week 28 up to Week 52 | 
| Time to First GCA Disease Flare or Discontinuation of Study Intervention due to AE of Worsening of GCA | The time to first GCA disease flare or discontinuation of study intervention due to AE of worsening of GCA will be assessed. Flare is defined as the recurrence of signs and symptoms of GCA, with or without elevation of inflammatory markers, and the necessity for an increase in GC dose for GCA. | Through Week 28 up to Week 52 | 
| Number of GCA Disease Flares or Discontinuation of Study Intervention due to AE of Worsening of GCA | Number of GCA disease flares or discontinuation of study intervention due to AE of worsening of GCA will be assessed. | Through Week 28 up to Week 52 | 
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) | An adverse event (AE) occurring at or after the initial administration of study intervention through the day of last dose plus 12 weeks (up to Week 60) is considered to be treatment emergent. An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An adverse event does not necessarily have a causal relationship with the intervention and can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product. | Up to Week 60 | 
| Number of Participants with TEAEs by System Organ Class With a Frequency Threshold of 5 percent (%) or More | An AE occurring at or after the initial administration of study intervention through the day of last dose plus 12 weeks is considered to be treatment emergent. An adverse event is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An adverse event does not necessarily have a causal relationship with the intervention and can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product. | Up to Week 60 | 
| Number of Participants with Treatment Emergent Serious Adverse Event (SAEs) | SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. | Up to Week 60 | 
| Number of Participants with Clinically Significant Abnormalities in Vital Signs | Number of participants with clinically significant abnormalities in vital signs (Temperature, pulse/heart rate, respiratory rate and blood pressure) will be assessed. | Up to Week 60 | 
| Number of Participants with Clinically Significant Abnormalities in Laboratory Parameters | Number of participants with clinically significant abnormalities in laboratory parameters (blood chemistry, hematology, coagulation, serology) will be assessed. | Up to Week 60 | 
| Serum Concentrations of Guselkumab | Serum concentrations of guselkumab will be assessed in participants receiving active study intervention. | Up to Week 52 | 
| Number of Participants with Antibodies to Guselkumab | Number of participants with antibodies to guselkumab will be assessed in participants receiving active study intervention. | Up to Week 60 |