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 Main Study: Percentage of Participants Achieving Glucocorticoid (GC)-Free Remission at Week 28 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.
- Secondary Outcome Measures
Name Time Method 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 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.
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 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.
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 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.
Main Study: Time to First GCA Disease Flare or Discontinuation of Study Intervention Due to Adverse Event (AE) of Worsening of GCA Baseline (Day 1) up to Week 30 and Week 52 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.
Main Study: Number of Participants With GCA Disease Flares or Discontinuation of Study Intervention Due to AE of Worsening of GCA Baseline (Day 1) up to Week 30 and Week 52 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.
Main Study: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters Baseline (Day 1) up to Week 60 Number of participants with National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade 3 or 4 abnormalities in clinical laboratory tests: hematology and chemistry were reported. Clinical laboratory abnormalities of living participants were assessed as per NCI CTCAE version 5, grades (0-4), where Grade 0-Normal, Grade 1- Mild, Grade 2- Moderate, Grade 3- Severe or medically significant but not immediately life-threatening, Grade 4- Life-threatening consequences. Higher grades showed severe abnormality. As per the discretion of investigator, laboratory abnormalities with NCI CTCAE Grade 3 or 4 were considered clinically significant. Combined data of Grade 3 and 4 abnormalities are reported as planned. Only those categories in which at least 1 participant had data were reported.
Main Study: Number of Participants With Antibodies to Guselkumab Baseline (Day 1) up to Week 28, Week 52 Number of participants with antibodies to Guselkumab were reported.
Main Study: Percentage of Participants Achieving GC-Free Remission at Weeks 28, 32, 36, 40, 44, 48 and 52 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.
Main Study: Cumulative Glucocorticoid (GC) Dose Baseline (Day 1) up to Weeks 28 and 52 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.
Main Study: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Baseline (Day 1) up to Week 60 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.
Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More Baseline (Day 1) up to Week 60 Number of participants with TEAEs (including serious and non-serious AEs) by SOC with a frequency threshold of 5 percent (%) or more were reported. An adverse event (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.
Main Study: Number of Participants With Treatment-emergent Serious Adverse Event (SAEs) Baseline (Day 1) up to Week 60 Number of participants with treatment emergent SAEs were reported. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurred at or after the initial administration of study intervention through the end of the main study was considered to be treatment emergent.
Main Study: Number of Participants With Clinically Significant Abnormalities in Vital Signs Baseline (Day 1) up to Week 60 Number of participants with clinically significant abnormalities in vital signs were reported. Clinically significant abnormal vital signs criteria: Pulse rate: \<50 beats per minutes (bpm) and with greater than (\>) 20 bpm decrease from baseline, \>115 bpm and with \>30 bpm increase from baseline; Systolic blood pressure (SBP): \<90 millimeters of mercury \[mmHg\] and with \>30 mmHg decrease from baseline, \>150 mmHg and with \>40 mmHg increase from baseline; Diastolic blood pressure (DBP): \<50 mmHg and with \>20 mmHg decrease from baseline, \>95 mmHg and with \>30 mmHg increase from baseline; Interarm blood pressure: Interarm blood pressure difference greater than or equal to (\>=) 15 mmHg in systolic blood pressure at 3 consecutive visits; Temperature (Temp): \>38.4 Degree Celsius (C) and with \>=1 C increase from baseline; Weight (kilogram \[kg\]): decrease 10 percent (%) from baseline, increase 10% from baseline; Respiratory Rate: \>20 breaths per minute.
Main Study: Serum Concentrations of Guselkumab Pre-dose and 1 hour post dose on Week 0 (Day 1), Week 4 (Day 28), and Week 8 (Day 56); Week 12 (Day 84), Week 16 (Day 112), Week 28 (Day 196), Week 52 (Day 364) Serum concentrations of Guselkumab over time was reported.
Trial Locations
- Locations (30)
Hosp Univ A Coruna
🇪🇸A Coruna, Spain
Hosp Regional Univ de Malaga
🇪🇸Malaga, 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
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