A Study to Evaluate Guselkumab for the Treatment of Participants With New-onset or Relapsing Giant Cell Arteritis
- Registration Number
- NCT04633447
- Lead Sponsor
- Janssen Research & Development, LLC
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 53
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo 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. Guselkumab Guselkumab 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Glucocorticoid (GC)-Free Remission At Week 28 Percentage of participants achieving GC-free remission will be assessed.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving GC-Free Remission and Normalization of Erythrocyte Sedimentation Rate (ESR) At Week 28 and up to Week 52 Percentage of participants achieving GC-free remission and normalization of ESR will be assessed using the Westergren method.
Percentage of Participants Achieving GC-Free Remission and Normalization of C-Reactive Protein (CRP) At Week 28 and up to Week 52 Percentage of participants achieving GC-free remission and normalization of CRP will be assessed.
Percentage of Participants Achieving GC-Free Remission and Normalization of Both ESR and CRP At Week 28 and up to Week 52 Percentage of participants achieving normalization of both ESR and CRP will be assessed.
Time to First GCA Disease Flare or Discontinuation of Study Intervention due to AE of Worsening of GCA Through Week 28 up to Week 52 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.
Number of GCA Disease Flares or Discontinuation of Study Intervention due to AE of Worsening of 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 will be assessed.
Number of Participants with Treatment Emergent Adverse Events (TEAEs) Up to Week 60 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.
Percentage of Participants Achieving GC-Free Remission From Week 28 up to Week 52 Percentage of participants achieving GC-free remission will be assessed.
Cumulative GC dose Through Week 28 up to Week 52 Cumulative GC dose will be assessed.
Number of Participants with Clinically Significant Abnormalities in Laboratory Parameters Up to Week 60 Number of participants with clinically significant abnormalities in laboratory parameters (blood chemistry, hematology, coagulation, serology) will be assessed.
Number of Participants with TEAEs by System Organ Class With a Frequency Threshold of 5 percent (%) or More Up to Week 60 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.
Number of Participants with Treatment Emergent Serious Adverse Event (SAEs) Up to Week 60 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.
Number of Participants with Clinically Significant Abnormalities in Vital Signs Up to Week 60 Number of participants with clinically significant abnormalities in vital signs (Temperature, pulse/heart rate, respiratory rate and blood pressure) will be assessed.
Number of Participants with Antibodies to Guselkumab Up to Week 60 Number of participants with antibodies to guselkumab will be assessed in participants receiving active study intervention.
Serum Concentrations of Guselkumab Up to Week 52 Serum concentrations of guselkumab will be assessed in participants receiving active study intervention.
Trial Locations
- Locations (30)
Hosp Regional Univ de Malaga
🇪🇸Malaga, Spain
Hosp Univ A Coruna
🇪🇸A Coruna, Spain
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Cliniques Universitaires St-Luc
🇧🇪Brussel, 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
Universitatsklinik Tubingen
🇩🇪Tubingen, Germany
Bnai Zion Medical Center
🇮🇱Hifa, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Rabin Medical Center Beilinson Campus
🇮🇱Petah Tikva, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Azianeda Ospedaliera dell'alto adige - Ospedale di Brunico
🇮🇹Bolzano, Italy
Ospedale San Raffaele
🇮🇹Milan, Italy
Azienda Ospedaliera di Padova
🇮🇹Padova, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Azienda USL 4 Prato
🇮🇹Prato, Italy
ASUI Santa Maria della Misericordia di Udine
🇮🇹Udine, Italy
Szpital Uniwersytecki Nr 2 w Bydgoszczy
🇵🇱Bydgoszcz, Poland
Szpital Specjalistyczny im. J. Dietla
🇵🇱Krakow, Poland
Hosp Clinic de Barcelona
🇪🇸Barcelona, Spain
NZOZ Lecznica MAK MED S C
🇵🇱Nadarzyn, Poland
Hosp. Clinico San Carlos
🇪🇸Madrid, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Hosp. Univ. Marques de Valdecilla
🇪🇸Santander, Spain