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

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

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).

Study Overview

• Status: Terminated
• Conditions: Giant Cell Arteritis
• Intervention / Treatment: Drug: Placebo; Drug: Guselkumab

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.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 3L9
      • Mount Sinai Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Hôpital du Sacré-Coeur de Montréal
• France
  • Dijon, France, 21000
    • CHU Dijon
  • Paris, France, 75014
    • Hopital Cochin
• Germany
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
  • Kirchheim unter Teck, Germany, 73230
    • medius KLINIK KIRCHHEIM
  • Tubingen, Germany, 72076
    • Universitätsklinik Tübingen
• Israel
  • Hifa, Israel, 31048
    • Bnai Zion Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center Beilinson Campus
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Italy
  • Bolzano, Italy, 39100
    • Azianeda Ospedaliera dell'alto adige - Ospedale di Brunico
  • Milan, Italy, 20132
    • Ospedale San Raffaele
  • Padova, Italy, 35121
    • Azienda Ospedaliera di Padova
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo
  • Prato, Italy, 59100
    • Azienda USL 4 Prato
  • Udine, Italy, 33100
    • ASUI Santa Maria della Misericordia di Udine
• Poland
  • Bydgoszcz, Poland, 85 168
    • Szpital Uniwersytecki Nr 2 w Bydgoszczy
  • Krakow, Poland, 31-121
    • Szpital Specjalistyczny im. J. Dietla
  • Nadarzyn, Poland, 05 830
    • NZOZ Lecznica MAK MED S C
• Spain
  • A Coruna, Spain, 15006
    • Hosp Univ A Coruna
  • Barcelona, Spain, 08036
    • Hosp Clinic de Barcelona
  • Madrid, Spain, 28040
    • Hosp. Clinico San Carlos
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Malaga, Spain, 29009
    • Hosp Regional Univ de Malaga
  • Santander, Spain, 39008
    • Hosp. Univ. Marques de Valdecilla
• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Guselkumab; Guselkumab will be administered subcutaneously.; Other Names: Tremfya; CNTO 1959
Experimental: 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.	Drug: Placebo; Matching placebo will be administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Weeks 28, 32, 36, 40, 44, 48 and 52
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.	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.	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.	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.	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.	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.	Baseline (Day 1) up to Week 60
Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More	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.	Baseline (Day 1) up to Week 60
Main Study: Number of Participants With Treatment-emergent Serious Adverse Event (SAEs)	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.	Baseline (Day 1) up to Week 60
Main Study: Number of Participants With Clinically Significant Abnormalities in Vital Signs	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.	Baseline (Day 1) up to Week 60
Main Study: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters	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.	Baseline (Day 1) up to Week 60
Main Study: Serum Concentrations of Guselkumab	Serum concentrations of Guselkumab over time was reported.	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)
Main Study: Number of Participants With Antibodies to Guselkumab	Number of participants with antibodies to Guselkumab were reported.	Baseline (Day 1) up to Week 28, Week 52

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2020
• Primary Completion (Actual): May 22, 2024
• Study Completion (Actual): May 22, 2024

Study Registration Dates

• First Submitted: November 6, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 26, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Muscular Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Skin Diseases; Skin Diseases, Vascular; Vasculitis; Vasculitis, Central Nervous System; Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis
• Other Study ID Numbers: CR108887; 2020-000622-26 (EudraCT Number); CNTO1959GCA2001 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No