Clinical trial NCT04633447: A Study to Evaluate Guselkumab for the Treatment of Participants With New-onset or Relapsing Giant Cell Arteritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Giant Cell Arteritis
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-11-18
Enrollment: 53
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Achieving Glucocorticoid (GC)-Free Remission
timeFrame: At Week 28
Secondary outcomes:
measure: Percentage of Participants Achieving GC-Free Remission
timeFrame: From Week 28 up to Week 52
measure: Percentage of Participants Achieving GC-Free Remission and Normalization of Erythrocyte Sedimentation Rate (ESR)
timeFrame: At Week 28 and up to Week 52
measure: Percentage of Participants Achieving GC-Free Remission and Normalization of C-Reactive Protein (CRP)
timeFrame: At Week 28 and up to Week 52
measure: Percentage of Participants Achieving GC-Free Remission and Normalization of Both ESR and CRP
timeFrame: At Week 28 and up to Week 52
measure: Cumulative GC dose
timeFrame: Through Week 28 up to Week 52
measure: Time to First GCA Disease Flare or Discontinuation of Study Intervention due to AE of Worsening of GCA
timeFrame: Through Week 28 up to Week 52
measure: Number of GCA Disease Flares or Discontinuation of Study Intervention due to AE of Worsening of GCA
timeFrame: Through Week 28 up to Week 52
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Week 60
measure: Number of Participants with TEAEs by System Organ Class With a Frequency Threshold of 5 percent (%) or More
timeFrame: Up to Week 60
measure: Number of Participants with Treatment Emergent Serious Adverse Event (SAEs)
timeFrame: Up to Week 60
measure: Number of Participants with Clinically Significant Abnormalities in Vital Signs
timeFrame: Up to Week 60
measure: Number of Participants with Clinically Significant Abnormalities in Laboratory Parameters
timeFrame: Up to Week 60
measure: Serum Concentrations of Guselkumab
timeFrame: Up to Week 52
measure: Number of Participants with Antibodies to Guselkumab
timeFrame: Up to Week 60
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Brussel
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Dijon
country: France
facility: CHU Dijon
city: Paris
country: France
facility: Hopital Cochin
city: Erlangen
country: Germany
facility: Universitatsklinikum Erlangen
city: Kirchheim unter Teck
country: Germany
facility: medius KLINIK KIRCHHEIM
city: Tubingen
country: Germany
facility: Universitatsklinik Tubingen
city: Hifa
country: Israel
facility: Bnai Zion Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center Beilinson Campus
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bolzano
country: Italy
facility: Azianeda Ospedaliera dell'alto adige - Ospedale di Brunico
city: Milan
country: Italy
facility: Ospedale San Raffaele
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Prato
country: Italy
facility: Azienda USL 4 Prato
city: Udine
country: Italy
facility: ASUI Santa Maria della Misericordia di Udine
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki Nr 2 w Bydgoszczy
city: Krakow
country: Poland
facility: Szpital Specjalistyczny im. J. Dietla
city: Nadarzyn
country: Poland
facility: NZOZ Lecznica MAK MED S C
city: A Coruna
country: Spain
facility: Hosp Univ A Coruna
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Madrid
country: Spain
facility: Hosp. Clinico San Carlos
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Malaga
country: Spain
facility: Hosp Regional Univ de Malaga
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: