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

NCT04882072 | Terminated Phase 3 Results DMC

• 2 other identifiers: CR108981CNTO1275TAT3001
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 27

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).

Conditions

Takayasu Arteritis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (20)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  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)

  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

  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

  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

  From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)

Study Arms (2)

Ustekinumab

EXPERIMENTAL

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; Drug: Glucorticoid Taper Regimen

Placebo

PLACEBO COMPARATOR

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; Other: Placebo; Drug: Glucorticoid Taper Regimen

Interventions

Ustekinumab DRUG

Participants will receive IV infusion and SC injection of ustekinumab.

Also known as: Stelara®, CNTO1275

Placebo; Ustekinumab

Placebo OTHER

Participants will receive IV infusion and SC injection of matching placebo.

Placebo

Glucorticoid Taper Regimen DRUG

Glucocorticoid will be administered orally.

Placebo; Ustekinumab

Eligibility Criteria

• Age: 15 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Pharmaceutical K.K.: lead

Study Sites (27)

Tokyo Medical and Dental University Hospital

Bunkyō City, 113 8519, Japan

Location

Chiba University Hospital

Chiba, 260 8677, Japan

Location

Kyushu University Hospital

Fukuoka, 812 8582, Japan

Location

Hamamatsu University Hospital

Hamamatsu, 431 3192, Japan

Location

Saitama Medical University Hospital

Iruma-gun, 350-0495, Japan

Location

Kagawa University Hospital

Kita Gun, 761 0793, Japan

Location

Kobe University Hospital

Kobe, 650 0017, Japan

Location

Kyoto University Hospital

Kyoto, 606-8507, Japan

Location

Matsuyama Red Cross Hospital

Matsuyama, 790-8524, Japan

Location

Nagoya City University Hospital

Nagoya, 467 8602, Japan

Location

Niigata University Medical And Dental Hospital

Niigata, 951 8520, Japan

Location

Okayama University Hospital

Okayama, 700 8558, Japan

Location

Kitano Hospital

Osaka, 530-8480, Japan

Location

Rinku General Medical Center

Osaka, 598-8577, Japan

Location

Kindai University Hospital

Osaka Sayama Shi, 589 8511, Japan

Location

Kitasato University Hospital

Sagamihara, 252-0375, Japan

Location

Sapporo Medical University Hospital

Sapporo, 060-8543, Japan

Location

Hokkaido University Hospital

Sapporo, 060-8648, Japan

Location

Tohoku University Hospital

Sendai, 980 8574, Japan

Location

Center Hospital of the National Center for Global Health and Medicine

Shinjuku Ku, 162 8655, Japan

Location

National Cerebral and Cardiovascular Center

Suita-Shi, 564-8565, Japan

Location

Mitsui Memorial Hospital

Tokyo, 101-8643, Japan

Location

St. Luke's International Hospital

Tokyo, 104 8560, Japan

Location

Fujita Health University Hospital

Toyoake, 470-1192, Japan

Location

University of Tsukuba Hospital

Tsukuba, 305 8576, Japan

Location

Wakayama Medical University Hospital

Wakayama, 641 8510, Japan

Location

Tottori University Hospital

Yonago, 683-8504, Japan

Location

Related Publications (1)

• Yoshifuji H, Ishii T, Ohashi H, Yoshizawa K, Mihoya M, Nishikawa K, Nakaoka Y. Phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study of ustekinumab in patients with Takayasu arteritis. Rheumatol Adv Pract. 2025 Feb 3;9(2):rkaf013. doi: 10.1093/rap/rkaf013. eCollection 2025.

  PMID: 40104212 DERIVED

MeSH Terms

Conditions

Takayasu Arteritis

Interventions

Ustekinumab

Condition Hierarchy (Ancestors)

Aortic Arch Syndromes; Aortic Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was terminated early by the sponsor due to difficulties in participant recruitment.

Results Point of Contact

• Title: Senior Director GI Clinical Development
• Organization: Janssen Pharmaceutical K.K.

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Pharmaceutical K.K., Japan Clinical Trial

  Janssen Pharmaceutical K.K.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 11, 2021
• Study Start: September 15, 2021
• Primary Completion: May 25, 2023
• Study Completion: May 25, 2023
• Last Updated: April 29, 2025
• Results First Posted: December 2, 2024

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

JP (27)