A Study of Ustekinumab in Participants With Takayasu Arteritis (TAK)

Takayasu Arteritis Clinical Trial

Official title:

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Ustekinumab in Participants With Takayasu Arteritis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04882072
• Other study ID #: CR108981
• Secondary ID: CNTO1275TAT3001
• Status: Terminated
• Phase: Phase 3
• Start date: September 15, 2021
• Est. completion date: May 25, 2023

Study information

• Verified date: July 2023
• Source: Janssen Pharmaceutical K.K.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of ustekinumab compared to placebo, in combination with oral glucocorticoid (GC) taper regimen, in participants with relapsing Takayasu Arteritis (TAK).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: May 25, 2023
• Est. primary completion date: May 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 75 Years

Eligibility

Inclusion Criteria:

• Must have developed a relapse of Takayasu Arteritis (TAK) within 12 weeks prior to administration of study intervention and the relapse must have occurred at a dose of at least 7.5 milligrams (mg)/day (prednisolone or equivalent)

• Must be receiving oral glucorticoid (GC) treatment of greater than or equal to (>=)15 mg/day (prednisolone or equivalent), inclusive for the treatment of relapsing TAK and be on a stable dose for at least 2 weeks prior to the first administration of study intervention

• If receiving an oral anti-platelet therapy (including but not limited to aspirin, clopidogrel, ticlopidine) or anti-coagulation therapy (including but not limited to warfarin) for treatment of TAK, the dose must have been stable for at least 2 weeks prior to first administration of the study intervention. In terms of warfarin, the dose should be controlled 1-5mg/day to maintain Prothrombin Time and International Normalized Ratio (PT-INR) target range between 2.0-3.0 (if participants are over 70 years old, PT-INR target range should be between 1.6-2.6)

• Have no history of latent or active Tuberculosis (TB) prior to screening. An exception is made for participants who have a history of latent TB and are currently receiving treatment for latent TB, will initiate treatment for latent TB at least 3 weeks prior to the first administration of the study intervention, or have documentation of having completed appropriate treatment for latent TB within 3 years prior to the first administration of the study intervention. It is the responsibility of the investigator to verify the adequacy of previous antituberculous treatment and provide appropriate documentation

• If receiving an oral anti-hypertensive therapy for treatment of TAK, the dose must have been stable for at least 2 weeks prior to first administration of the study intervention

Exclusion Criteria:

• Has currently any known severe or uncontrolled TAK complications (example, hypertension not responding to adequate treatment, aortic incompetence with cardiac insufficiency, progressing aortic aneurysm, coronary artery lesions with severe stenosis)

• Has received immunosuppressant (s) (including but not limited to Methotrexate [MTX], Azathioprine [AZA], Mycophenolate Mofetil [MMF], oral Triamcinolone [TAC], oral Cyclosporine A) within 4 weeks of first study intervention

• Has had a Bacille Calmette-guerin (BCG) vaccination within 12 months of screening

• Any major illness/condition or evidence of an unstable clinical condition example, history of liver or renal insufficiency (estimated creatinine clearance below 60 milliliters/minute [mL/min]); significant (cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances), disease of any organ system or active acute or chronic infection/infectious illness that, in the investigator's judgment, will substantially increase the risk to the participant if he or she participates in the study

• Having a condition that is steroid dependent (example, steroid dependent asthma, chronic obstructive pulmonary disease, et cetera) that is not amenable to tapering oral GC

Related Conditions & MeSH terms

• Arteritis
• Takayasu Arteritis

Intervention

Drug:
• Ustekinumab
Participants will receive IV infusion and SC injection of ustekinumab.

Other:
• Placebo
Participants will receive IV infusion and SC injection of matching placebo.

Drug:
• Glucorticoid Taper Regimen
Glucocorticoid will be administered orally.

Locations

Country	Name	City	State
Japan	Tokyo Medical and Dental University Hospital	Bunkyo-Ku
Japan	Chiba University Hospital	Chiba
Japan	Kyushu University Hospital	Fukuoka
Japan	Hamamatsu University Hospital	Hamamatsu
Japan	Saitama Medical University Hospital	Iruma-gun
Japan	Kagawa University Hospital	Kita-Gun
Japan	Kobe University Hospital	Kobe
Japan	Kyoto University Hospital	Kyoto
Japan	Matsuyama Red Cross Hospital	Matsuyama-City
Japan	Nagoya City University Hospital	Nagoya-City
Japan	Niigata University Medical & Dental Hospital	Niigata
Japan	Okayama University Hospital	Okayama
Japan	Kitano Hospital	Osaka
Japan	Rinku General Medical Center	Osaka
Japan	Kindai University Hospital	Osaka-Sayama-shi
Japan	Kitasato University Hospital	Sagamihara
Japan	Sapporo Medical University Hospital	Sapporo
Japan	Hokkaido University Hospital	Sapporo-shi
Japan	Tohoku University Hospital	Sendai
Japan	National Cerebral and Cardiovascular Center	Suita-Shi
Japan	Mitsui Memorial Hospital	Tokyo
Japan	National Center for Global Health and Medicine	Tokyo
Japan	St. Luke's International Hospital	Tokyo
Japan	Fujita Health University Hospital	Toyoake
Japan	University of Tsukuba Hospital	Tsukuba
Japan	Wakayama Medical University Hospital	Wakayama
Japan	Tottori University Hospital	Yonago

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Pharmaceutical K.K.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Relapse Through the End of Double-blind (DB) Period	Time to relapse is defined as the assessment of 'signs of relapse present' as judged by the investigator for at least 2 of 5 categories: objective systemic symptoms, subjective systemic symptoms, elevated inflammation markers, vascular signs and symptoms, or ischemic symptoms.	Up to occurrence of 35 events (Up to 24 months)
Secondary	Number of Participants with Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment.	Up to 3 years
Secondary	Number of Participants with TEAEs by System Organ Class (SOC) with a Frequency Threshold of 5 Percent (%) or More	An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment.	Up to 3 years
Secondary	Number of Participants with Treatment-emergent Serious Adverse Events (SAEs)	SAE is any untoward medical occurrence that at any dose may 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. Treatment-emergent SAEs are defined as SAEs with onset or worsening on or after date of first dose of study treatment.	Up to 3 years
Secondary	Time to Relapse of TAK by Kerr's Criteria Through the End of DB Period	Time to relapse is defined as the assessment of 'signs of relapse present as judged by the investigator for at least 2 of 4 categories: systemic symptoms (objective or subjective), elevated inflammation markers, vascular signs, and symptoms and ischemic symptoms.	Up to occurrence of 35 events (Up to 24 months)
Secondary	Time to Relapse Based on Clinical Symptoms Through the End of DB Period	Time to relapse based on clinical symptoms through the end of DB period will be reported. Participants who meet at least 1 category in the following 4 clinical categories will be considered as relapse per clinical symptom: 1) Objective systemic symptoms; 2) Subjective systemic symptoms; 3) Vascular signs and symptoms; 4) Ischemic symptoms.	Up to occurrence of 35 events (Up to 24 months)
Secondary	Time to Relapse of TAK in Each of the 5 Categories Through the End of DB Period	Time to relapse is defined as the assessment of 'signs of relapse present' as judged by the investigator in each of the 5 categories: objective systemic symptoms, subjective systemic symptoms, elevated inflammation markers, vascular signs and symptoms, or ischemic symptoms.	Up to occurrence of 35 events (Up to 24 months)
Secondary	Percentage of Participants with Relapse in Each of the 5 Categories Through the End of DB Period	Percentage of participants with relapse in each of the 5 categories (objective systemic symptoms, subjective systemic symptoms, elevated inflammation markers, vascular signs and symptoms, or ischemic symptoms) through the end of DB period will be reported.	Up to occurrence of 35 events (Up to 24 months)
Secondary	Cumulative Oral Glucocorticoid (GC) Dose Through the End of DB Period	Cumulative oral GC dose (prednisolone or equivalent) through the end of DB period will be reported.	Up to occurrence of 35 events (Up to 24 months)
Secondary	Change from Baseline in Oral GC Dose Through the End of DB Period	Change from baseline in oral GC dose (prednisolone or equivalent) through the end of DB period will be reported.	Baseline; up to the end of DB period (Up to 24 months)
Secondary	Number of Participants Achieving GC Dose of 5 milligrams (mg)/day or Less Through the End of DB Period	Number of participants achieving GC dose of 5 mg/day or less at the end of DB period will be reported.	Up to 24 months
Secondary	Number of Participants with Change from Baseline in Imaging Evaluation Through the End of DB Period	Number of participants with change from baseline in imaging evaluation through the end of DB period will be reported. Vessel involvement such as stenosis, obstruction, and aneurysm; arterial wall thickness; and the presence of mural contrast enhancement and oedema will be assessed for imaging evaluation using magnetic resonance angiography (MRA).	Baseline, every 24 weeks from Week 0 and relapse confirmation visit (Up to 24 months)
Secondary	Change from Baseline in C-reactive Protein (CRP) Through the End of DB Period	Change from baseline in CRP through the end of DB period will be reported.	Baseline; up to 24 months
Secondary	Change from Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of DB Period	Change from baseline in ESR through the end of DB period will be reported.	Baseline; up to 24 months
Secondary	Serum Concentrations of Ustekinumab	Serum concentrations of ustekinumab will be reported.	Up to end of study (Up to 3 years)
Secondary	Number of Participants with Positive Anti-ustekinumab Antibodies	Number of participants with positive anti-ustekinumab antibodies will be reported.	Up to end of study (Up to 3 years)