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

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04633447
• Collaborator: (none)
• Enrollment: 51
• Locations: 34
• Arms: 2
• Anticipated Duration (Months): 41.7
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Giant Cell Arteritis	Drug: Guselkumab; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 10, 2020
• Anticipated Primary Completion Date: Aug 28, 2023
• Anticipated Study Completion Date: May 31, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving Glucocorticoid (GC)-Free Remission [At Week 28]

   Percentage of participants achieving GC-free remission will be assessed.

Secondary Outcome Measures

1. Percentage of Participants Achieving GC-Free Remission [From Week 28 up to Week 52]

   Percentage of participants achieving GC-free remission will be assessed.

2. 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.

3. 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.

4. 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.

5. Cumulative GC dose [Through Week 28 up to Week 52]

   Cumulative GC dose will be assessed.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. Serum Concentrations of Guselkumab [Up to Week 52]

    Serum concentrations of guselkumab will be assessed in participants receiving active study intervention.

14. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
3	Hospital for Special Surgery	New York	New York	United States	10021
4	Cliniques Universitaires St-Luc	Brussel		Belgium	1200
5	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
6	Mount Sinai Hospital	Toronto	Ontario	Canada	M5T 3L9
7	Hopital du Sacre-Coeur de Montreal	Montreal	Quebec	Canada	H4J 1C5
8	CHU de Brest - Hôpital de la Cavale Blanche	Brest		France	29200
9	CHU caen	Caen		France	14033
10	CHU Dijon	Dijon		France	21000
11	Hopital Cochin	Paris		France	75014
12	Universitätsklinikum Erlangen	Erlangen		Germany	91054
13	Medizinische Hochschule Hannover	Hannover		Germany	30625
14	medius KLINIK KIRCHHEIM	Kirchheim unter Teck		Germany	73230
15	Universitatsklinik Tubingen	Tubingen		Germany	72076
16	Bnai Zion Medical Center	Hifa		Israel	31048
17	Hadassah Medical Center	Jerusalem		Israel	91120
18	Rabin Medical Center, Beilinson Campus	Petah Tikva		Israel	49100
19	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239
20	Azianeda Ospedaliera dell'alto adige - Ospedale di Brunico	Bolzano		Italy	39100
21	Ospedale San Raffaele	Milan		Italy	20132
22	Azienda Ospedaliera di Padova	Padova		Italy	35121
23	Fondazione IRCCS Policlinico San Matteo	Pavia		Italy	27100
24	Azienda USL 4 Prato	Prato		Italy	59100
25	ASUI Santa Maria della Misericordia di Udine	Udine		Italy	33100
26	Szpital Uniwersytecki Nr 2 w Bydgoszczy	Bydgoszcz		Poland	85-168
27	Szpital Specjalistyczny im. J. Dietla	Krakow		Poland	31-121
28	NZOZ Lecznica MAK-MED. S.C.	Nadarzyn		Poland	05-830
29	Hosp. Univ. A Coruña	A Coruña		Spain	15006
30	Hosp. Clinic I Provincial de Barcelona	Barcelona		Spain	08036
31	Hosp. Clinico San Carlos	Madrid		Spain	28040
32	Hosp. Univ. 12 de Octubre	Madrid		Spain	28041
33	Hosp. Regional Univ. de Malaga	Málaga		Spain	29009
34	Hosp. Univ. Marques de Valdecilla	Santander		Spain	39008

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT04633447
• Other Study ID Numbers: CR108887; 2020-000622-26; CNTO1959GCA2001
• First Posted: Nov 18, 2020
• Last Update Posted: Aug 12, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis

Study Results

No Results Posted as of Aug 12, 2022