Clinical trial NCT04882072: A Study of Ustekinumab in Participants With Takayasu Arteritis (TAK)
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Ustekinumab in Participants With Takayasu Arteritis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Takayasu Arteritis
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2021-05-11
Enrollment: 14
Sex: ALL
Minimum age (years): 15
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: Time to Relapse (ToR) of Takayasu Arteritis (TAK) According to Protocol-defined Criteria Through the End of Double-blind Period
timeFrame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Double-blind period: Double-blind Week 0 up to end of double-blind treatment period (56.1 weeks); OLE period: OL Week 0 up to end of OLE treatment period (48.1 weeks)
measure: Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: Double-blind period: Double-blind Week 0 up to end of double-blind treatment period (56.1 weeks); OLE: OL Week 0 up to end of OLE treatment period (48.1 weeks)
measure: Time to Relapse of TAK According to Kerr's Criteria Through the End of Double-blind Period
timeFrame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
measure: Time to Relapse of TAK Based on Clinical Symptoms Through the End of Double-blind Period
timeFrame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
measure: Time to Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period
timeFrame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
measure: Percentage of Participants With Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period
timeFrame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
measure: Cumulative Oral Glucocorticoid (GC) Dose Through the End of Double-blind Period
timeFrame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
measure: Change From Baseline in Oral GC Dose Through the End of Double-blind Period
timeFrame: Baseline (double-blind Week 0) up to end of double-blind period (up to 71.1 weeks)
measure: Number of Participants Achieving GC Dose of 5 mg/Day or Less Through the End of Double-blind Period
timeFrame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
measure: Change From Baseline in Imaging Evaluation of Vessel Involvement (Average Percentage of Dilation) at the End of Double-blind Period
timeFrame: Baseline (double-blind Week 0) and double-blind relapse (up to 14 weeks for Placebo arm; up to 48 weeks for ustekinumab arm)
measure: Change From Baseline in Imaging Evaluation of Vessel Involvement (Average Percentage of Stenosis) Through the End of Double-blind Period
timeFrame: Baseline (double-blind Week 0), Week 24, Week 48, and double-blind relapse (up to 14 weeks for Placebo arm; up to 48 weeks for ustekinumab arm)
measure: Change From Baseline in Imaging Evaluation of Average Arterial Wall Thickness Through the End of Double-blind Period
timeFrame: Baseline (double-blind Week 0), Week 24, Week 48, and double-blind relapse (up to 14 weeks for Placebo arm; up to 48 weeks for ustekinumab arm)
measure: Imaging Evaluation: Number of Participants With Mural Contrast Enhancement Through the End of Double-blind Period
timeFrame: Baseline (double-blind Week 0), Week 24, Week 48, and double-blind relapse (up to 14 weeks for Placebo arm; up to 48 weeks for ustekinumab arm)
measure: Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period
timeFrame: Baseline (double-blind Week 0), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, and double-blind relapse (up to 14 weeks for Placebo arm; up to 48 weeks for ustekinumab arm)
measure: Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period
timeFrame: Baseline (double-blind Week 0), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, and double-blind relapse (up to 14 weeks for Placebo arm; up to 48 weeks for ustekinumab arm)
measure: Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase
timeFrame: Pre-dose (double-blind Week 0), Post-dose: Week 0, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, double-blind relapse (up to 48 weeks)
measure: Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase
timeFrame: Pre-dose (OL Week 0), Post-dose: OL Week 0, OL Weeks 8, 16, 24, 32, 40, 48, 52, and 56
measure: Number of Participants With Positive Anti-ustekinumab Antibodies Through End of Double-blind Period
timeFrame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
measure: Number of Participants With Positive Anti-ustekinumab Antibodies Through End of OLE Period
timeFrame: From OL Week 0 up to end of OLE period (up to 63.1 weeks)
measure: Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More
timeFrame: Double-blind period: double-blind Week 0 up to end of double-blind treatment period (56.1 weeks); OLE period: OL Week 0 up to end of OLE treatment period (48.1 weeks)
Other outcomes:
Locations:
city: Bunkyo Ku
country: Japan
facility: Tokyo Medical and Dental University Hospital
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hamamatsu
country: Japan
facility: Hamamatsu University Hospital
city: Iruma-gun
country: Japan
facility: Saitama Medical University Hospital
city: Kita Gun
country: Japan
facility: Kagawa University Hospital
city: Kobe
country: Japan
facility: Kobe University Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Matsuyama-City
country: Japan
facility: Matsuyama Red Cross Hospital
city: Nagoya City
country: Japan
facility: Nagoya City University Hospital
city: Niigata
country: Japan
facility: Niigata University Medical And Dental Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka Sayama shi
country: Japan
facility: Kindai University Hospital
city: Osaka
country: Japan
facility: Kitano Hospital
city: Osaka
country: Japan
facility: Rinku General Medical Center
city: Sagamihara
country: Japan
facility: Kitasato University Hospital
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
city: Sendai
country: Japan
facility: Tohoku University Hospital
city: Shinjuku ku
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine
city: Suita-Shi
country: Japan
facility: National Cerebral and Cardiovascular Center
city: Tokyo
country: Japan
facility: Mitsui Memorial Hospital
city: Tokyo
country: Japan
facility: St. Luke's International Hospital
city: Toyoake
country: Japan
facility: Fujita Health University Hospital
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital
city: Yonago
country: Japan
facility: Tottori University Hospital
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trial
role: STUDY_DIRECTOR
References: