Takayasu ArteritisPhase 3NCT04882072
A Study of Ustekinumab in Participants With Takayasu Arteritis (TAK)
A Phase 3 study testing Ustekinumab and Glucorticoid Taper Regimen in people with Takayasu Arteritis, run by Janssen Pharmaceutical K.K. at 27 sites in Japan.
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). Read more about this study
- Who is it for?
- Ages 15 to 75 years
- Conditions the study is for
- Takayasu Arteritis
- What is being tested?
- Ustekinumab and Glucorticoid Taper Regimen
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 27 sitesJapan
- Study dates
- 15 Sep 2021to 25 May 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
27 sites in 1 country.
27 sites in 1 country
Japan27 sites
Tokyo Medical and Dental University Hospital
Bunkyō City, 113 8519
Chiba University Hospital
Chiba, 260 8677
Kyushu University Hospital
Fukuoka, 812 8582
Hamamatsu University Hospital
Hamamatsu, 431 3192
Saitama Medical University Hospital
Iruma-gun, 350-0495
Kagawa University Hospital
Kita Gun, 761 0793
Kobe University Hospital
Kobe, 650 0017
Kyoto University Hospital
Kyoto, 606-8507
Matsuyama Red Cross Hospital
Matsuyama, 790-8524
Nagoya City University Hospital
Nagoya, 467 8602
Niigata University Medical And Dental Hospital
Niigata, 951 8520
Okayama University Hospital
Okayama, 700 8558
Kitano Hospital
Osaka, 530-8480
Rinku General Medical Center
Osaka, 598-8577
Kindai University Hospital
Osaka Sayama Shi, 589 8511
Kitasato University Hospital
Sagamihara, 252-0375
Sapporo Medical University Hospital
Sapporo, 060-8543
Hokkaido University Hospital
Sapporo, 060-8648
Tohoku University Hospital
Sendai, 980 8574
Center Hospital of the National Center for Global Health and Medicine
Shinjuku Ku, 162 8655
National Cerebral and Cardiovascular Center
Suita-Shi, 564-8565
Mitsui Memorial Hospital
Tokyo, 101-8643
St. Luke's International Hospital
Tokyo, 104 8560
Fujita Health University Hospital
Toyoake, 470-1192
University of Tsukuba Hospital
Tsukuba, 305 8576
Wakayama Medical University Hospital
Wakayama, 641 8510
Tottori University Hospital
Yonago, 683-8504
About this study
Official title: 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).
- Conditions
- Takayasu Arteritis
- Being tested
- Ustekinumab, Placebo, Glucorticoid Taper Regimen
- Medical subject headings
- Takayasu Arteritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UstekinumabDrug
Also called Stelara®, CNTO1275
Participants will receive IV infusion and SC injection of ustekinumab.
PlaceboOther
Participants will receive IV infusion and SC injection of matching placebo.
Glucorticoid Taper RegimenDrug
Glucocorticoid will be administered orally.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Ustekinumab; Other: Placebo; Drug: Glucorticoid Taper Regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2021
- Study start15 Sep 2021
- Primary completion25 May 2023
- Study completion25 May 2023
Why it stopped: Due to difficulties in enrollment and ongoing feasibility issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Takayasu ArteritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Pharmaceutical K.K.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Pharmaceutical K.K., Japan Clinical Trial, Study director, Janssen Pharmaceutical K.K.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04882072
- Sponsor's protocol ID
- CR108981
- Other IDs
- CNTO1275TAT3001
- Status last verified
- Apr 2025
- First submitted
- 10 May 2021
- Last updated
- 29 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
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.
PubMed 40104212
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Ustekinumab in Participants With Takayasu Arteritis
- ClinicalTrials.gov ID
- NCT04882072
- Acronym / sponsor ID
- CR108981
- Conditions
- Takayasu Arteritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to difficulties in enrollment and ongoing feasibility issues
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Janssen Pharmaceutical K.K.Industry (pharma, biotech, devices)
- Study start
- 15 Sep 2021 (actual)
- Primary completion
- 25 May 2023 (actual)
- Study completion
- 25 May 2023 (actual)
- First posted
- 11 May 2021 (actual)
- Results
- Posted 2 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ustekinumab | Experimental | Drug: Ustekinumab, Drug: Glucorticoid Taper RegimenDouble-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. |
| Placebo | Placebo comparator | Drug: Ustekinumab, Other: Placebo, Drug: Glucorticoid Taper RegimenDB 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. |
Who may qualify
- Ages
- 15 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UstekinumabAlso: Stelara®, CNTO1275Participants will receive IV infusion and SC injection of ustekinumab. | Drug | Placebo, Ustekinumab |
| PlaceboParticipants will receive IV infusion and SC injection of matching placebo. | Other | Placebo |
| Glucorticoid Taper RegimenGlucocorticoid will be administered orally. | Drug | Placebo, Ustekinumab |
Primary outcome
Time to Relapse (ToR) of Takayasu Arteritis (TAK) According to Protocol-defined Criteria Through the End of Double-blind Period
Time frame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
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.
20 secondary outcomes
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: 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)
Time frame: 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
Time frame: 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 frame: 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 frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40104212Yoshifuji 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.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Pharmaceutical K.K., Japan Clinical Trial study director
Janssen Pharmaceutical K.K.
27 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ustekinumab and Glucorticoid Taper Regimen in people with Takayasu Arteritis, run by Janssen Pharmaceutical K.K. at 27 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Relapse (ToR) of Takayasu Arteritis (TAK) According to Protocol-defined Criteria Through the End of Double-blind Period (time frame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04882072, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2025.