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

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

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).

Study Overview

• Status: Terminated
• Conditions: Takayasu Arteritis
• Intervention / Treatment: Drug: Ustekinumab; Drug: Glucorticoid Taper Regimen; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Bunkyo Ku, Japan, 113 8519
    • Tokyo Medical and Dental University Hospital
  • Chiba, Japan, 260 8677
    • Chiba University Hospital
  • Fukuoka, Japan, 812 8582
    • Kyushu University Hospital
  • Hamamatsu, Japan, 431 3192
    • Hamamatsu University Hospital
  • Iruma-gun, Japan, 350-0495
    • Saitama Medical University Hospital
  • Kita Gun, Japan, 761 0793
    • Kagawa University Hospital
  • Kobe, Japan, 650 0017
    • Kobe University Hospital
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Matsuyama-City, Japan, 790-8524
    • Matsuyama Red Cross Hospital
  • Nagoya City, Japan, 467 8602
    • Nagoya City University Hospital
  • Niigata, Japan, 951 8520
    • Niigata University Medical And Dental Hospital
  • Okayama, Japan, 700 8558
    • Okayama University Hospital
  • Osaka, Japan, 530-8480
    • Kitano Hospital
  • Osaka, Japan, 598-8577
    • Rinku General Medical Center
  • Osaka Sayama shi, Japan, 589 8511
    • Kindai University Hospital
  • Sagamihara, Japan, 252-0375
    • Kitasato University Hospital
  • Sapporo, Japan, 060-8543
    • Sapporo Medical University Hospital
  • Sapporo-shi, Japan, 060-8648
    • Hokkaido University Hospital
  • Sendai, Japan, 980 8574
    • Tohoku University Hospital
  • Shinjuku ku, Japan, 162 8655
    • Center Hospital of the National Center for Global Health and Medicine
  • Suita-Shi, Japan, 564-8565
    • National Cerebral and Cardiovascular Center
  • Tokyo, Japan, 101-8643
    • Mitsui Memorial Hospital
  • Tokyo, Japan, 104 8560
    • St. Luke's International Hospital
  • Toyoake, Japan, 470-1192
    • Fujita Health University Hospital
  • Tsukuba, Japan, 305 8576
    • University of Tsukuba Hospital
  • Wakayama, Japan, 641 8510
    • Wakayama Medical University Hospital
  • Yonago, Japan, 683-8504
    • Tottori University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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: Ustekinumab; Double-blind (DB) Period: Participants will receive weight-ranged based ustekinumab (6 milligrams/kilogram[mg/kg]) as IV infusion at Week 0 followed by ustekinumab 90mg injection SC 8 weeks after initial IV dose, then every 8 weeks (q8w) thereafter until the end of the DB period with starting the protocol defined oral GC taper regimen from Week 2 visit. Open Label Extension (OLE) period: Participants will receive ustekinumab SC injection at Week OL-0, followed by ustekinumab 90mg SC injection with oral GC taper at investigator's discretion for 52 weeks (Week OL-52) or until 32 weeks from first SC administration after end of DB period whichever is later. Long-term Extension (LTE) Period: Participants who completed OLE period may be eligible to enter LTE and continue to receive ustekinumab 90mg SC injection q8w.	Drug: Ustekinumab; Participants will receive IV infusion and SC injection of ustekinumab.; Other Names: Stelara®; CNTO1275; Drug: Glucorticoid Taper Regimen; Glucocorticoid will be administered orally.
Placebo Comparator: Placebo; DB period: Participants will receive placebo intravenous (IV) infusion at Week 0 followed by placebo subcutaneous (SC) injection administration, 8 weeks after the initial IV dose, then q8w thereafter until the end of DB period with starting the protocol defined oral GC taper regimen from Week 2 visit. OLE period: Participants will receive ustekinumab SC at Week OL-0, followed by SC administration of ustekinumab with oral GC taper at investigator's discretion for 52 weeks (Week OL-52) or until 32 weeks from the first SC administration after the end of DB period, whichever is later. LTE Period: Participants who complete their participation in OLE period may be eligible to enter the LTE and continue to receive 90 mg SC ustekinumab q8w.	Drug: Ustekinumab; Participants will receive IV infusion and SC injection of ustekinumab.; Other Names: Stelara®; CNTO1275; Drug: Glucorticoid Taper Regimen; Glucocorticoid will be administered orally.; Other: Placebo; Participants will receive IV infusion and SC injection of matching placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Relapse (ToR) of Takayasu Arteritis (TAK) According to Protocol-defined Criteria Through the End of Double-blind Period	ToR:time from randomization to 1st relapse through end of double-blind period (EDBP) per protocol-defined criteria with 5 categories:systemic (objective):body temperature >=38.0°C, weight loss >2kg in 4 weeks, arthralgia, swelling & tenderness =>2 joints; systemic (subjective):malaise, myalgia, headache, dizziness/vertigo at >= grade 2, high inflammation markers (C-reactive protein >=1.0mg/dL, erythrocyte sedimentation rate >=30mm/hr), vascular symptoms:renovascular hypertension: if normal BP <120/80mmHg risen to >=140/90mmHg, or if normal BP >=120/80mmHg, diastolic BP risen by >=20mmHg, new bruits/loss of pulse/difference in systolic BP between left and right by >=10mmHg/tenderness/spontaneous pain in carotid artery/chest/back region, aortic valve incompetence; ischemic symptoms:abdominal pain, seizure, syncope, intermittent claudication, ischemic cardiac pain. Relapse:>=2 categories met criteria.	From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study intervention. TEAEs were defined as AEs with onset or worsening on or after date of first dose of study intervention through the day of last dose.	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)
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 were defined as SAEs with onset or worsening on or after date of first dose of study intervention through the day of last dose.	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)
Time to Relapse of TAK According to Kerr's Criteria Through the End of Double-blind Period	ToR was defined from the date of randomization to the judged date of relapse through the EDBP based on Kerr's definition: participants who met 2 or more categories in the following 4 categories were considered as relapse: systemic (objective):body temperature >=38.0°C, weight loss >2kg in 4 weeks, arthralgia, swelling & tenderness =>2 joints; systemic (subjective):malaise, myalgia, headache, dizziness/vertigo at >= grade 2, high inflammation markers (C-reactive protein >=1.0mg/dL, erythrocyte sedimentation rate >=30mm/hr), vascular symptoms:renovascular hypertension: if normal BP <120/80mmHg risen to >=140/90mmHg, or if normal BP >=120/80mmHg, diastolic BP risen by >=20mmHg, new bruits/loss of pulse/difference in systolic BP between left and right by >=10mmHg/tenderness/spontaneous pain in carotid artery/chest/back region, aortic valve incompetence; ischemic symptoms:abdominal pain, seizure, syncope, intermittent claudication, ischemic cardiac pain.	From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Time to Relapse of TAK Based on Clinical Symptoms Through the End of Double-blind Period	Time (in weeks) to relapse of TAK: time from randomization to the 1st relapse through the EDBP according to protocol-defined criteria with 5 categories: systemic (objective):body temperature >=38.0°C, weight loss >2kg in 4 weeks, arthralgia, swelling and tenderness =>2 joints; systemic (subjective):malaise, myalgia, headache, dizziness/vertigo at >= grade 2, high inflammation markers (C-reactive protein >=1.0mg/dL, erythrocyte sedimentation rate >=30mm/hr), vascular symptoms:renovascular hypertension: if normal BP <120/80mmHg risen to >=140/90mmHg, or if normal BP >=120/80mmHg, diastolic BP risen by >=20mmHg, new bruits/loss of pulse/difference in systolic BP between left and right by >=10mmHg/tenderness/spontaneous pain in carotid artery/chest/back region, aortic valve incompetence; ischemic symptoms:abdominal pain, seizure, syncope, intermittent claudication, ischemic cardiac pain. Time to relapse was calculated by each category independently. Relapse:>=2 categories met criteria.	From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Time to Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period	Time to relapse of TAK: time from randomization date to the 1st relapse through the EDBP according to protocol-defined criteria with 5 categories: systemic (objective):body temperature >=38.0°C, weight loss >2kg in 4 weeks, arthralgia, swelling and tenderness =>2 joints; systemic (subjective):malaise, myalgia, headache, dizziness/vertigo at >= grade 2, high inflammation markers (C-reactive protein >=1.0mg/dL, erythrocyte sedimentation rate >=30mm/hr), vascular symptoms:renovascular hypertension: if normal BP <120/80mmHg risen to >=140/90mmHg, or if normal BP >=120/80mmHg, diastolic BP risen by >=20mmHg, new bruits/loss of pulse/difference in systolic BP between left and right by >=10mmHg/tenderness/spontaneous pain in carotid artery/chest/back region, aortic valve incompetence; ischemic symptoms:abdominal pain, seizure, syncope, intermittent claudication, ischemic cardiac pain. Time to relapse was calculated by each category independently. Relapse:>=2 categories met criteria.	From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Percentage of Participants With Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period	Percentage of participants with time to relapse of TAK through the EDBP were reported. Protocol-defined criteria consisted of 5 categories: systemic (objective):body temperature >=38.0°C, weight loss >2kg in 4 weeks, arthralgia, swelling & tenderness =>2 joints; systemic (subjective):malaise, myalgia, headache, dizziness/vertigo at >= grade 2, high inflammation markers (C-reactive protein >=1.0mg/dL, erythrocyte sedimentation rate >=30mm/hr), vascular symptoms:renovascular hypertension: if normal BP <120/80mmHg risen to >=140/90mmHg, or if normal BP >=120/80mmHg, diastolic BP risen by >=20mmHg, new bruits/loss of pulse/difference in systolic BP between left and right by >=10mmHg/tenderness/spontaneous pain in carotid artery/chest/back region, aortic valve incompetence; ischemic symptoms: abdominal pain, seizure, syncope, intermittent claudication, ischemic cardiac pain.	From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Cumulative Oral Glucocorticoid (GC) Dose Through the End of Double-blind Period	Cumulative oral GC dose (prednisolone or equivalent) through the end of double-blind period were reported. If the participant had relapse, oral GC dose (prednisolone or equivalent) used from randomization date to last observed date prior to the date of relapse were included in the analysis and if the participant had no relapse then oral GC dose used from randomization to last observed date through the end of double-blind period were included in the analysis.	From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Change From Baseline in Oral GC Dose Through the End of Double-blind Period	Change from baseline in oral GC dose through the end of double-blind period were reported. Change from baseline was defined as the change between the GC dose at randomization and the last observed GC dose. If the participant had relapse, oral GC dose (prednisolone or equivalent) used from randomization date to last observed date prior to the date of relapse were included in the analysis and if the participant had no relapse then oral GC dose used from randomization to last observed date through the end of double-blind period were included in the analysis.	Baseline (double-blind Week 0) up to end of double-blind period (up to 71.1 weeks)
Number of Participants Achieving GC Dose of 5 mg/Day or Less Through the End of Double-blind Period	Number of participants who achieved GC dose of 5 mg/day or less through the end of double-blind period were reported.	From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Change From Baseline in Imaging Evaluation of Vessel Involvement (Average Percentage of Dilation) at the End of Double-blind Period	Change from baseline in average percentage of dilation for abnormal vessel segments through the end of double-blind period was reported. Assessment was performed using computed tomography angiography (CTA) or magnetic resonance angiography (MRA). For a participant, the time point at which the 1st relapse developed or discontinuation from double-blind period was considered as the end of double-blind period.	Baseline (double-blind Week 0) and double-blind relapse (up to 14 weeks for Placebo arm; up to 48 weeks for ustekinumab arm)
Change From Baseline in Imaging Evaluation of Vessel Involvement (Average Percentage of Stenosis) Through the End of Double-blind Period	Change from baseline in average percentage of stenosis for abnormal vessel segments through the end of double-blind period was reported. Assessment was performed using CTA or MRA. For a participant, the time point at which the 1st relapse developed or discontinuation from double-blind period was considered as the end of double-blind period.	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)
Change From Baseline in Imaging Evaluation of Average Arterial Wall Thickness Through the End of Double-blind Period	Change from baseline in average wall thickness for abnormal segments through the end of double-blind period was reported. Assessment was performed using CTA or MRA. For a participant, the time point at which the 1st relapse developed or discontinuation from double-blind period was considered as the end of double-blind period.	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)
Imaging Evaluation: Number of Participants With Mural Contrast Enhancement Through the End of Double-blind Period	Number of participants with mural contrast enhancement through the end of double-blind period were reported. The mural contrast enhancement were assessed for imaging evaluation using CTA or MRA. For a participant, the time point at which the 1st relapse developed or discontinuation from double-blind period was considered as the end of double-blind period.	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)
Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period	Change from baseline in CRP (as inflammatory marker) through the end of double-blind period were reported. For a participant, the time point at which the 1st relapse developed or discontinuation from double-blind period was considered as the end of double-blind period.	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)
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period	Change from baseline in ESR (as inflammatory marker) through the end of double-blind period were reported. For a participant, the time point at which the 1st relapse developed or discontinuation from double-blind period was considered as the end of double-blind period.	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)
Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase	Serum concentrations of ustekinumab was reported during double-blind Phase. For a participant, the time point at which the 1st relapse developed or discontinuation from double-blind period was considered as the end of double-blind period.	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)
Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase	Serum concentrations of ustekinumab was reported during OLE Phase.	Pre-dose (OL Week 0), Post-dose: OL Week 0, OL Weeks 8, 16, 24, 32, 40, 48, 52, and 56
Number of Participants With Positive Anti-ustekinumab Antibodies Through End of Double-blind Period	Number of participants with positive anti-ustekinumab antibodies were reported.	From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Number of Participants With Positive Anti-ustekinumab Antibodies Through End of OLE Period	Number of participants with positive anti-ustekinumab antibodies were reported.	From OL Week 0 up to end of OLE period (up to 63.1 weeks)
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 with the study intervention. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study intervention through the day of last dose. If same participant had more than one AE within the same SOC, that participant is counted only once in the below data table.	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)

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutical K.K.
• Investigators: Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial, Janssen Pharmaceutical K.K.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Actual): May 25, 2023
• Study Completion (Actual): May 25, 2023

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Actual): April 29, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Skin Diseases; Skin Diseases, Vascular; Aortic Diseases; Vasculitis; Arteritis; Takayasu Arteritis; Aortic Arch Syndromes; Dermatologic Agents; Ustekinumab
• Other Study ID Numbers: CR108981; CNTO1275TAT3001 (Other Identifier: Janssen Pharmaceutical K.K., Japan)

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