A Study of Ustekinumab in Participants With Takayasu Arteritis (TAK)
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| 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:
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:
Other: Placebo
Participants will receive IV infusion and SC injection of matching placebo.
Drug: Glucorticoid Taper Regimen
Glucocorticoid will be administered orally.
|
Outcome Measures
Primary Outcome Measures
- Time to Relapse Through the End of Double-blind (DB) Period [Up to occurrence of 35 events (Up to 24 months)]
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.
Secondary Outcome Measures
- Number of Participants with Treatment Emergent Adverse Events (TEAEs) [Up to 3 years]
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.
- Number of Participants with TEAEs by System Organ Class (SOC) with a Frequency Threshold of 5 Percent (%) or More [Up to 3 years]
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.
- Number of Participants with Treatment-emergent Serious Adverse Events (SAEs) [Up to 3 years]
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.
- Time to Relapse of TAK by Kerr's Criteria Through the End of DB Period [Up to occurrence of 35 events (Up to 24 months)]
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.
- Time to Relapse Based on Clinical Symptoms Through the End of DB Period [Up to occurrence of 35 events (Up to 24 months)]
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.
- Time to Relapse of TAK in Each of the 5 Categories Through the End of DB Period [Up to occurrence of 35 events (Up to 24 months)]
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.
- Percentage of Participants with Relapse in Each of the 5 Categories Through the End of DB Period [Up to occurrence of 35 events (Up to 24 months)]
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.
- Cumulative Oral Glucocorticoid (GC) Dose Through the End of DB Period [Up to occurrence of 35 events (Up to 24 months)]
Cumulative oral GC dose (prednisolone or equivalent) through the end of DB period will be reported.
- Change from Baseline in Oral GC Dose Through the End of DB Period [Baseline; up to the end of DB period (Up to 24 months)]
Change from baseline in oral GC dose (prednisolone or equivalent) through the end of DB period will be reported.
- Number of Participants Achieving GC Dose of 5 milligrams (mg)/day or Less Through the End of DB Period [Up to 24 months]
Number of participants achieving GC dose of 5 mg/day or less at the end of DB period will be reported.
- Number of Participants with Change from Baseline in Imaging Evaluation Through the End of DB Period [Baseline, every 24 weeks from Week 0 and relapse confirmation visit (Up to 24 months)]
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).
- Change from Baseline in C-reactive Protein (CRP) Through the End of DB Period [Baseline; up to 24 months]
Change from baseline in CRP through the end of DB period will be reported.
- Change from Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of DB Period [Baseline; up to 24 months]
Change from baseline in ESR through the end of DB period will be reported.
- Serum Concentrations of Ustekinumab [Up to end of study (Up to 3 years)]
Serum concentrations of ustekinumab will be reported.
- Number of Participants with Positive Anti-ustekinumab Antibodies [Up to end of study (Up to 3 years)]
Number of participants with positive anti-ustekinumab antibodies will be reported.
Eligibility Criteria
Criteria
Inclusion Criteria:
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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)
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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
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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)
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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
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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:
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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)
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Has received Methotrexate (MTX), Azathioprine (AZA), Mycophenolate Mofetil (MMF), oral Triamcinolone (TAC), oral Cyclosporine A within 4 weeks of first study intervention
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Has had a Bacille Calmette-guerin (BCG) vaccination within 12 months of screening
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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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tokyo Medical and Dental University Hospital | Bunkyo-Ku | Japan | 113-8519 | |
| 2 | Chiba University Hospital | Chiba | Japan | 260-8677 | |
| 3 | Kyushu University Hospital | Fukuoka | Japan | 812-8582 | |
| 4 | Hamamatsu University Hospital | Hamamatsu | Japan | 431-3192 | |
| 5 | Saitama Medical University Hospital | Iruma-gun | Japan | 350-0495 | |
| 6 | Kagoshima University Hospital | Kagoshima City | Japan | 890-8544 | |
| 7 | Kagawa University Hospital | Kita-Gun | Japan | 761-0793 | |
| 8 | Kobe University Hospital | Kobe | Japan | 650-0017 | |
| 9 | Kyoto University Hospital | Kyoto | Japan | 606-8507 | |
| 10 | Matsuyama Red Cross Hospital | Matsuyama-City | Japan | 790-8524 | |
| 11 | Nagoya City University Hospital | Nagoya-City | Japan | 467-8602 | |
| 12 | Niigata University Medical & Dental Hospital | Niigata | Japan | 951-8520 | |
| 13 | Okayama University Hospital | Okayama | Japan | 700-8558 | |
| 14 | Kindai University Hospital | Osaka-Sayama-shi | Japan | 589-8511 | |
| 15 | Kitano Hospital | Osaka | Japan | 530-8480 | |
| 16 | Rinku General Medical Center | Osaka | Japan | 598-8577 | |
| 17 | Kitasato University Hospital | Sagamihara | Japan | 252-0375 | |
| 18 | Hokkaido University Hospital | Sapporo-shi | Japan | 060-8648 | |
| 19 | Sapporo Medical University Hospital | Sapporo | Japan | 060-8543 | |
| 20 | Tohoku University Hospital | Sendai | Japan | 980-8574 | |
| 21 | National Cerebral and Cardiovascular Center Hospital | Suita-Shi | Japan | 564-8565 | |
| 22 | Mitsui Memorial Hospital | Tokyo | Japan | 101-8643 | |
| 23 | St. Luke's International Hospital | Tokyo | Japan | 104-8560 | |
| 24 | National Center for Global Health and Medicine | Tokyo | Japan | 162-8655 | |
| 25 | The Sakakibara Heart Institute | Tokyo | Japan | 183-0003 | |
| 26 | Fujita Health University Hospital | Toyoake | Japan | 470-1192 | |
| 27 | University of Tsukuba Hospital | Tsukuba | Japan | 305-8576 | |
| 28 | Wakayama Medical University Hospital | Wakayama | Japan | 641-8510 | |
| 29 | Tottori University Hospital | Yonago | Japan | 683-8504 |
Sponsors and Collaborators
- Janssen Pharmaceutical K.K.
Investigators
- Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial, Janssen Pharmaceutical K.K.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR108981
- CNTO1275TAT3001