Takayasu Arteritis
Conditions
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).
Interventions
DRUGUstekinumab
Participants will receive IV infusion and SC injection of ustekinumab.
OTHERPlacebo
Participants will receive IV infusion and SC injection of matching placebo.
DRUGGlucorticoid Taper Regimen
Glucocorticoid will be administered orally.
Sponsors
Janssen Pharmaceutical K.K.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
15 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Relapse (ToR) of Takayasu Arteritis (TAK) According to 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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. |
| 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) | 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. |
| 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 (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. |
| 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) | 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. |
| Percentage of Participants With 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) | 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. |
| Cumulative Oral Glucocorticoid (GC) Dose Through the End of Double-blind Period | From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks) | 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. |
| Change From Baseline in Oral GC Dose Through the End of Double-blind Period | Baseline (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 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. |
| Number of Participants Achieving GC Dose of 5 mg/Day or Less Through the End of Double-blind Period | From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks) | Number of participants who achieved GC dose of 5 mg/day or less through the end of double-blind period were reported. |
| Number of Participants With Positive Anti-ustekinumab Antibodies Through End of OLE Period | From OL Week 0 up to end of OLE period (up to 63.1 weeks) | Number of participants with positive anti-ustekinumab antibodies were reported. |
| 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) | 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. |
| Change From Baseline in Imaging Evaluation of Vessel Involvement (Average Percentage of Stenosis) Through 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 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. |
| Change From Baseline in Imaging Evaluation of Average Arterial Wall Thickness Through 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 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. |
| Imaging Evaluation: Number of Participants With Mural Contrast Enhancement Through 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) | 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. |
| Change From Baseline in C-reactive Protein (CRP) Through 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 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. |
| Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through 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 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. |
| Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | 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 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. |
| Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | Pre-dose (OL Week 0), Post-dose: OL Week 0, OL Weeks 8, 16, 24, 32, 40, 48, 52, and 56 | Serum concentrations of ustekinumab was reported during OLE Phase. |
| Number of Participants With Positive Anti-ustekinumab Antibodies Through End of Double-blind Period | 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 were reported. |
| Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | 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) | 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. |
| Change From Baseline in Imaging Evaluation of Vessel Involvement (Average Percentage of Dilation) at 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 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. |
Countries
Japan
Participant flow
Pre-assignment details
Due to the early study termination, participants who had relapse during double blind period were only able to enter open label extension (OLE) period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Then Ustekinumab In the double blind-period, participants received placebo matched to ustekinumab as intravenous (IV) infusion at Week 0 followed by placebo subcutaneous (SC) injection at Week 8 and thereafter every 8 weeks (q8w) until developing relapse or end of double blind period (up to 8.1 weeks), with starting the protocol defined oral glucocorticoid (GC) taper regimen from Week 2. Upon relapse, participants received rescue medication of greater than or equal to (\>=) doubled oral GC dose. These participants were assessed whether they achieved remission at the next scheduled dose administration visit (open label \[OL\] Week 0) from the relapse to enter OLE period and then they received ustekinumab 90 mg IV infusion at OL Week 0 followed by ustekinumab 90 mg SC injection at OL Week 8 and thereafter q8w in OLE period (maximum exposure: 48.1 weeks). Rest of the participants entered OLE period after end of double blind-period and received ustekinumab 90 mg SC injection (maintenance dosing) q8w from OL Week 0 (maximum exposure: 48.1 weeks). Participants who reached oral GC dose of 5 mg/day or less at the end of double blind period were terminated from study intervention administration and underwent early-term visit after completion of double blind period. | 8 |
| Ustekinumab Then Ustekinumab In the double-blind period, participants received body weight-range based ustekinumab (6 mg/kg) IV infusion at Week 0 followed by ustekinumab 90 mg SC injection at Week 8 and thereafter q8w until developing relapse or end of double-blind period (maximum exposure: 56.1 weeks), with starting the protocol defined oral GC taper regimen from Week 2. Upon relapse, participants received rescue medication of \>=doubled oral GC dose. These participants were assessed whether they achieved remission at the next scheduled dose administration visit (OL Week 0) from the relapse to enter OLE period and then they received ustekinumab 90 mg IV infusion at OL Week 0 followed by ustekinumab 90 mg SC injection at OL Week 8 and thereafter q8w in OLE period (maximum exposure: 48.1 weeks). Rest of the participants entered OLE period after end of double-blind period and received ustekinumab 90 mg SC injection (maintenance dosing) q8w from OL Week 0 (maximum exposure: 48.1 weeks). | 6 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double Blind: Week 0 to Week 71.1 | Withdrawal by Subject | 1 | 0 |
| Double Blind: Week 0 to Week 71.1 | Withdrawal Criterion Met | 1 | 0 |
| OL Extension: OL Week 0 to OL Week 63.1 | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo Then Ustekinumab | Ustekinumab Then Ustekinumab | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 12 Participants |
| Age, Continuous | 49.6 years STANDARD_DEVIATION 15.46 | 36.5 years STANDARD_DEVIATION 12.19 | 44 years STANDARD_DEVIATION 15.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 6 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 6 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Female | 7 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 6 / 8 | 5 / 6 | 1 / 3 | 2 / 4 |
| serious Total, serious adverse events | 1 / 8 | 1 / 6 | 0 / 3 | 1 / 4 |
Outcome results
Primary
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.
Time frame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Population: Full analysis set (FAS) included all randomized participants who received at least 1 dose of study intervention through double-blind period. Censored:death/discontinued drugs at last assessment through EDBP (before relapse)/before EDBP (no relapse).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Double-blind: Placebo | Time to Relapse (ToR) of Takayasu Arteritis (TAK) According to Protocol-defined Criteria Through the End of Double-blind Period | 12.64 Weeks |
| Double-blind: Ustekinumab | Time to Relapse (ToR) of Takayasu Arteritis (TAK) According to Protocol-defined Criteria Through the End of Double-blind Period | 11.14 Weeks |
95% CI: [0.41, 8.47]
Secondary
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.
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)
Population: FAS includes all randomized participants who received at least 1 dose of study intervention through double-blind period. Here, '0' in the number analyzed field of arm 'Double-blind: Placebo', signifies that no participant was available for analysis because all placebo group participants either relapsed or discontinued the study before Week 24. Here, 'n' (number analyzed) signifies number of participants analyzed at each specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind: Placebo | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 2 | -0.003 milligrams per deciliter (mg/dL) | Standard Deviation 0.0539 |
| Double-blind: Placebo | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 8 | 0.918 milligrams per deciliter (mg/dL) | Standard Deviation 1.3851 |
| Double-blind: Placebo | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 12 | 1.475 milligrams per deciliter (mg/dL) | Standard Deviation 0.5132 |
| Double-blind: Placebo | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Relapse | 2.043 milligrams per deciliter (mg/dL) | Standard Deviation 1.5661 |
| Double-blind: Placebo | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 4 | 0.529 milligrams per deciliter (mg/dL) | Standard Deviation 1.4639 |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 20 | -0.030 milligrams per deciliter (mg/dL) | — |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 24 | 0.00 milligrams per deciliter (mg/dL) | — |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 28 | 0.00 milligrams per deciliter (mg/dL) | — |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 32 | 0.310 milligrams per deciliter (mg/dL) | — |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 36 | 0.060 milligrams per deciliter (mg/dL) | — |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 40 | -0.020 milligrams per deciliter (mg/dL) | — |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 44 | 0.300 milligrams per deciliter (mg/dL) | — |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 48 | -0.010 milligrams per deciliter (mg/dL) | — |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 52 | 0.010 milligrams per deciliter (mg/dL) | — |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 56 | 0.130 milligrams per deciliter (mg/dL) | — |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 8 | 0.333 milligrams per deciliter (mg/dL) | Standard Deviation 0.3505 |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Relapse | 2.598 milligrams per deciliter (mg/dL) | Standard Deviation 3.2988 |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 2 | 0.558 milligrams per deciliter (mg/dL) | Standard Deviation 0.9585 |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 4 | 0.858 milligrams per deciliter (mg/dL) | Standard Deviation 1.6216 |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 12 | 1.170 milligrams per deciliter (mg/dL) | Standard Deviation 1.0333 |
| Double-blind: Ustekinumab | Change From Baseline in C-reactive Protein (CRP) Through the End of Double-blind Period | Double-blind Week 16 | -0.010 milligrams per deciliter (mg/dL) | — |
Secondary
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.
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)
Population: FAS includes all randomized participants who received at least 1 dose of study intervention through double-blind period. Here, '0' in the number analyzed field of Double-blind: Placebo arm signifies that no participant was available for analysis because all placebo group participants either relapsed or discontinued the study before Week 24. Here, 'n' (number analyzed) signifies number of participants analyzed at each specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind: Placebo | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 2 | 0.13 millimeters per hour (mm/h) | Standard Deviation 1.246 |
| Double-blind: Placebo | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 8 | 6.67 millimeters per hour (mm/h) | Standard Deviation 4.131 |
| Double-blind: Placebo | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 4 | 4.75 millimeters per hour (mm/h) | Standard Deviation 11.841 |
| Double-blind: Placebo | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Relapse | 28.25 millimeters per hour (mm/h) | Standard Deviation 15.5 |
| Double-blind: Placebo | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 12 | 24.25 millimeters per hour (mm/h) | Standard Deviation 15.174 |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 16 | 1.00 millimeters per hour (mm/h) | — |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 20 | -2.00 millimeters per hour (mm/h) | — |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 24 | -2.00 millimeters per hour (mm/h) | — |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 28 | 12.00 millimeters per hour (mm/h) | — |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 32 | 13.00 millimeters per hour (mm/h) | — |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 36 | 2.00 millimeters per hour (mm/h) | — |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 40 | 2.00 millimeters per hour (mm/h) | — |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 44 | 0.00 millimeters per hour (mm/h) | — |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 48 | -2.00 millimeters per hour (mm/h) | — |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 52 | -2.00 millimeters per hour (mm/h) | — |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 56 | 20.00 millimeters per hour (mm/h) | — |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Relapse | 18.63 millimeters per hour (mm/h) | Standard Deviation 9.741 |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 2 | 1.20 millimeters per hour (mm/h) | Standard Deviation 8.349 |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 4 | 4.33 millimeters per hour (mm/h) | Standard Deviation 17.397 |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 8 | 5.13 millimeters per hour (mm/h) | Standard Deviation 7.028 |
| Double-blind: Ustekinumab | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Through the End of Double-blind Period | Double-blind Week 12 | 15.50 millimeters per hour (mm/h) | Standard Deviation 15.174 |
Secondary
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.
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)
Population: FAS: who received at least 1 dose of study intervention through double-blind period. Here, '0' in the number analyzed field of 'Double-blind: Placebo' arm signifies that no participant was available for analysis because all placebo group participants either relapsed or discontinued the study before Week 24. Here, 'N' (number of participants analyzed): who were evaluable for this outcome measure and 'n' (number analyzed):number of participants analyzed at each specified timepoints.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Double-blind: Placebo | Change From Baseline in Imaging Evaluation of Average Arterial Wall Thickness Through the End of Double-blind Period | Double-blind Relapse | -1.00 millimeters |
| Double-blind: Ustekinumab | Change From Baseline in Imaging Evaluation of Average Arterial Wall Thickness Through the End of Double-blind Period | Double-blind Week 24 | -1.25 millimeters |
| Double-blind: Ustekinumab | Change From Baseline in Imaging Evaluation of Average Arterial Wall Thickness Through the End of Double-blind Period | Double-blind Week 48 | -1.25 millimeters |
| Double-blind: Ustekinumab | Change From Baseline in Imaging Evaluation of Average Arterial Wall Thickness Through the End of Double-blind Period | Double-blind Relapse | 1.00 millimeters |
Secondary
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.
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)
Population: FAS includes all randomized participants who received at least 1 dose of study intervention through double-blind period. Here, '0' in the number of participants analyzed field of arm 'Double-blind: Placebo' signifies that no participants were available for analysis because placebo group did not have abnormal dilation at double-blind relapse visit. Here, 'N' (number of participants analyzed): who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind: Ustekinumab | Change From Baseline in Imaging Evaluation of Vessel Involvement (Average Percentage of Dilation) at the End of Double-blind Period | -3.95 Percentage of Dilation | Standard Deviation 5.586 |
Secondary
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.
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)
Population: FAS: who received at least 1 dose of study intervention through double-blind period. Here, '0' in the number analyzed field of 'Double-blind: Placebo' arm signifies that no participant was available for analysis because all placebo group participants either relapsed or discontinued the study before Week 24. Here, 'N' (number of participants analyzed): who were evaluable for this outcome measure and 'n' (number analysed): number of participants analyzed at each specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind: Placebo | Change From Baseline in Imaging Evaluation of Vessel Involvement (Average Percentage of Stenosis) Through the End of Double-blind Period | Double-blind Relapse | -7.15 Percentage of Stenosis | Standard Deviation 10.105 |
| Double-blind: Ustekinumab | Change From Baseline in Imaging Evaluation of Vessel Involvement (Average Percentage of Stenosis) Through the End of Double-blind Period | Double-blind Week 24 | -11.39 Percentage of Stenosis | — |
| Double-blind: Ustekinumab | Change From Baseline in Imaging Evaluation of Vessel Involvement (Average Percentage of Stenosis) Through the End of Double-blind Period | Double-blind Week 48 | -12.62 Percentage of Stenosis | — |
| Double-blind: Ustekinumab | Change From Baseline in Imaging Evaluation of Vessel Involvement (Average Percentage of Stenosis) Through the End of Double-blind Period | Double-blind Relapse | -13.94 Percentage of Stenosis | Standard Deviation 22.24 |
Secondary
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.
Time frame: Baseline (double-blind Week 0) up to end of double-blind period (up to 71.1 weeks)
Population: FAS includes all randomized participants who received at least 1 dose of study intervention through double-blind period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind: Placebo | Change From Baseline in Oral GC Dose Through the End of Double-blind Period | -11.3 milligrams per day (mg/day) | Standard Deviation 3.73 |
| Double-blind: Ustekinumab | Change From Baseline in Oral GC Dose Through the End of Double-blind Period | -12.1 milligrams per day (mg/day) | Standard Deviation 6.25 |
Secondary
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.
Time frame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Population: FAS includes all randomized participants who received at least 1 dose of study intervention through double-blind period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind: Placebo | Cumulative Oral Glucocorticoid (GC) Dose Through the End of Double-blind Period | 1043.6 milligrams (mg) | Standard Deviation 367.27 |
| Double-blind: Ustekinumab | Cumulative Oral Glucocorticoid (GC) Dose Through the End of Double-blind Period | 1319.1 milligrams (mg) | Standard Deviation 697.67 |
Secondary
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.
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)
Population: FAS: who received at least 1 dose of study intervention through double-blind period. Here, '0' in the number analyzed field of Double-blind: Placebo arm signifies that no participant was available for analysis because all placebo group participants either relapsed or discontinued the study before Week 24. Here, 'N' (number of participants analyzed): who were evaluable for this outcome measure and 'n' (number analyzed): number of participants analyzed at each specified timepoints.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-blind: Placebo | Imaging Evaluation: Number of Participants With Mural Contrast Enhancement Through the End of Double-blind Period | Baseline (Week 0) | 1 Participants |
| Double-blind: Placebo | Imaging Evaluation: Number of Participants With Mural Contrast Enhancement Through the End of Double-blind Period | Double-blind Relapse | 0 Participants |
| Double-blind: Ustekinumab | Imaging Evaluation: Number of Participants With Mural Contrast Enhancement Through the End of Double-blind Period | Baseline (Week 0) | 1 Participants |
| Double-blind: Ustekinumab | Imaging Evaluation: Number of Participants With Mural Contrast Enhancement Through the End of Double-blind Period | Double-blind Week 24 | 1 Participants |
| Double-blind: Ustekinumab | Imaging Evaluation: Number of Participants With Mural Contrast Enhancement Through the End of Double-blind Period | Double-blind Week 48 | 1 Participants |
| Double-blind: Ustekinumab | Imaging Evaluation: Number of Participants With Mural Contrast Enhancement Through the End of Double-blind Period | Double-blind Relapse | 1 Participants |
Secondary
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.
Time frame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Population: FAS includes all randomized participants who received at least 1 dose of study intervention through double-blind period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind: Placebo | Number of Participants Achieving GC Dose of 5 mg/Day or Less Through the End of Double-blind Period | 3 Participants |
| Double-blind: Ustekinumab | Number of Participants Achieving GC Dose of 5 mg/Day or Less Through the End of Double-blind Period | 1 Participants |
Secondary
Number of Participants With Positive Anti-ustekinumab Antibodies Through End of Double-blind Period
Number of participants with positive anti-ustekinumab antibodies were reported.
Time frame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Population: The immunogenicity analysis set was defined as all participants who received at least 1 dose of ustekinumab and had at least 1 postdose valid immunogenicity data. For this outcome measure, as pre-planned, data collection and analysis was not performed for the placebo arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind: Placebo | Number of Participants With Positive Anti-ustekinumab Antibodies Through End of Double-blind Period | 0 Participants |
Secondary
Number of Participants With Positive Anti-ustekinumab Antibodies Through End of OLE Period
Number of participants with positive anti-ustekinumab antibodies were reported.
Time frame: From OL Week 0 up to end of OLE period (up to 63.1 weeks)
Population: The immunogenicity analysis set was defined as all participants who received at least 1 dose of ustekinumab and had at least 1 postdose valid immunogenicity data. In ustekinumab arm N included all participants who were initially randomized to ustekinumab arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind: Placebo | Number of Participants With Positive Anti-ustekinumab Antibodies Through End of OLE Period | 0 Participants |
| Double-blind: Ustekinumab | Number of Participants With Positive Anti-ustekinumab Antibodies Through End of OLE Period | 0 Participants |
Secondary
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.
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)
Population: The safety analysis set included all participants who received at least 1 dose of study intervention through double-blind period and OLE period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-blind: Placebo | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Nervous System Disorders | 0 Participants |
| Double-blind: Placebo | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Investigations | 0 Participants |
| Double-blind: Placebo | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Gastrointestinal Disorders | 3 Participants |
| Double-blind: Placebo | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | General Disorders and Administration Site Conditions | 0 Participants |
| Double-blind: Placebo | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Ear and Labyrinth Disorders | 0 Participants |
| Double-blind: Placebo | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Musculoskeletal and Connective Tissue Disorders | 1 Participants |
| Double-blind: Placebo | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Injury, Poisoning and Procedural Complications | 1 Participants |
| Double-blind: Placebo | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Eye Disorders | 2 Participants |
| Double-blind: Placebo | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Infections and Infestations | 1 Participants |
| Double-blind: Placebo | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Vascular Disorders | 1 Participants |
| Double-blind: Placebo | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Respiratory, Thoracic and Mediastinal Disorders | 0 Participants |
| Double-blind: Placebo | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Skin and Subcutaneous Tissue Disorders | 4 Participants |
| Double-blind: Placebo | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Metabolism and Nutrition Disorders | 0 Participants |
| Double-blind: Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Respiratory, Thoracic and Mediastinal Disorders | 0 Participants |
| Double-blind: Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Gastrointestinal Disorders | 0 Participants |
| Double-blind: Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Musculoskeletal and Connective Tissue Disorders | 1 Participants |
| Double-blind: Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Infections and Infestations | 6 Participants |
| Double-blind: Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Skin and Subcutaneous Tissue Disorders | 0 Participants |
| Double-blind: Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Injury, Poisoning and Procedural Complications | 3 Participants |
| Double-blind: Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Metabolism and Nutrition Disorders | 1 Participants |
| Double-blind: Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Investigations | 1 Participants |
| Double-blind: Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | General Disorders and Administration Site Conditions | 4 Participants |
| Double-blind: Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Ear and Labyrinth Disorders | 1 Participants |
| Double-blind: Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Vascular Disorders | 2 Participants |
| Double-blind: Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Eye Disorders | 2 Participants |
| Double-blind: Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Nervous System Disorders | 5 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Injury, Poisoning and Procedural Complications | 1 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | General Disorders and Administration Site Conditions | 0 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Infections and Infestations | 0 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Investigations | 0 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Ear and Labyrinth Disorders | 0 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Eye Disorders | 0 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Metabolism and Nutrition Disorders | 0 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Musculoskeletal and Connective Tissue Disorders | 0 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Gastrointestinal Disorders | 1 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Nervous System Disorders | 1 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Respiratory, Thoracic and Mediastinal Disorders | 0 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Skin and Subcutaneous Tissue Disorders | 0 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Vascular Disorders | 0 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Nervous System Disorders | 1 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Eye Disorders | 0 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Injury, Poisoning and Procedural Complications | 1 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Gastrointestinal Disorders | 2 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Respiratory, Thoracic and Mediastinal Disorders | 2 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Ear and Labyrinth Disorders | 0 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Infections and Infestations | 0 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Vascular Disorders | 1 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Skin and Subcutaneous Tissue Disorders | 0 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Musculoskeletal and Connective Tissue Disorders | 0 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Metabolism and Nutrition Disorders | 0 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | Investigations | 1 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More | General Disorders and Administration Site Conditions | 2 Participants |
Secondary
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.
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)
Population: The safety analysis set included all participants who received at least 1 dose of study intervention through double-blind period and OLE period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind: Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| Double-blind: Ustekinumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 5 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 1 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
Secondary
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.
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)
Population: The safety analysis set included all participants who received at least 1 dose of study intervention through double-blind period and OLE period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind: Placebo | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 1 Participants |
| Double-blind: Ustekinumab | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 1 Participants |
| OLE: Placebo Then Ustekinumab | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 0 Participants |
| OLE: Ustekinumab Then Ustekinumab | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 1 Participants |
Secondary
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.
Time frame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Population: FAS includes all randomized participants who received at least 1 dose of study intervention through double-blind period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-blind: Placebo | Percentage of Participants With Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Systemic Symptoms (Subjective Assessment) | 37.5 percentage of participants |
| Double-blind: Placebo | Percentage of Participants With Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Vascular Signs And Symptoms | 50.0 percentage of participants |
| Double-blind: Placebo | Percentage of Participants With Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Elevated Inflammation Markers | 50.0 percentage of participants |
| Double-blind: Placebo | Percentage of Participants With Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Ischemic Symptoms | 0 percentage of participants |
| Double-blind: Placebo | Percentage of Participants With Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Systemic Symptoms (Objective Assessment) | 25.0 percentage of participants |
| Double-blind: Ustekinumab | Percentage of Participants With Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Ischemic Symptoms | 0 percentage of participants |
| Double-blind: Ustekinumab | Percentage of Participants With Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Systemic Symptoms (Objective Assessment) | 16.7 percentage of participants |
| Double-blind: Ustekinumab | Percentage of Participants With Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Systemic Symptoms (Subjective Assessment) | 50.0 percentage of participants |
| Double-blind: Ustekinumab | Percentage of Participants With Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Elevated Inflammation Markers | 50.0 percentage of participants |
| Double-blind: Ustekinumab | Percentage of Participants With Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Vascular Signs And Symptoms | 100.0 percentage of participants |
Secondary
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.
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)
Population: The pharmacokinetic (PK) analysis set was defined as participants who received at least 1 complete dose of ustekinumab and had at least 1 valid postdose PK data. Here, 'n' (number analyzed) signifies number of participants analyzed at each specified timepoints. For this outcome measure, as pre-planned, data collection and analysis was not performed for the placebo arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 4 | 21.630 micrograms per millilitres (mcg/mL) | Standard Deviation 3.5437 |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Pre-dose (Week 0) | NA micrograms per millilitres (mcg/mL) | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Post-dose (Week 0) | 135.644 micrograms per millilitres (mcg/mL) | Standard Deviation 33.2099 |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 2 | 40.470 micrograms per millilitres (mcg/mL) | Standard Deviation 8.5492 |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 8 | 8.663 micrograms per millilitres (mcg/mL) | Standard Deviation 2.9795 |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 12 | 7.762 micrograms per millilitres (mcg/mL) | Standard Deviation 0.7537 |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 16 | 3.811 micrograms per millilitres (mcg/mL) | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 20 | 4.970 micrograms per millilitres (mcg/mL) | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 24 | 2.195 micrograms per millilitres (mcg/mL) | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 28 | 5.323 micrograms per millilitres (mcg/mL) | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 32 | 2.033 micrograms per millilitres (mcg/mL) | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 36 | 3.984 micrograms per millilitres (mcg/mL) | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 40 | 1.695 micrograms per millilitres (mcg/mL) | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 44 | 4.958 micrograms per millilitres (mcg/mL) | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 48 | 2.121 micrograms per millilitres (mcg/mL) | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 52 | 6.447 micrograms per millilitres (mcg/mL) | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 56 | 2.596 micrograms per millilitres (mcg/mL) | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Week 60 | 3.244 micrograms per millilitres (mcg/mL) | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Double-blind Phase | Double-blind: Relapse | 13.437 micrograms per millilitres (mcg/mL) | — |
Secondary
Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase
Serum concentrations of ustekinumab was reported during OLE Phase.
Time frame: Pre-dose (OL Week 0), Post-dose: OL Week 0, OL Weeks 8, 16, 24, 32, 40, 48, 52, and 56
Population: PK analysis set: who experienced relapse in double-blind period and received at least 1 complete dose of ustekinumab and had at least 1 valid postdose PK data from OL Week 0 to end of OLE period. Here, '0' in the number analyzed field of second arm signifies that no participant was available for analysis because all participants were relapsed before OL Week 48. Here, 'n' (number analyzed): number of participants analyzed at each specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | Post-dose OL Week 0 | 126.394 mcg/mL | Standard Deviation 15.5782 |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | OL Week 8 | 15.830 mcg/mL | Standard Deviation 7.3113 |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | OL Week 16 | 7.253 mcg/mL | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | OL Week 24 | 8.844 mcg/mL | Standard Deviation 4.3775 |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | OL Week 32 | 6.096 mcg/mL | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | OL Week 40 | 3.911 mcg/mL | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | OL Week 52 | 9.676 mcg/mL | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | OL Week 56 | 3.710 mcg/mL | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | OL Week 48 | 3.719 mcg/mL | — |
| Double-blind: Placebo | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | Pre-dose OL Week 0 | NA mcg/mL | — |
| Double-blind: Ustekinumab | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | Post-dose OL Week 0 | 132.580 mcg/mL | Standard Deviation 36.2574 |
| Double-blind: Ustekinumab | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | OL Week 16 | 7.560 mcg/mL | — |
| Double-blind: Ustekinumab | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | OL Week 32 | 3.870 mcg/mL | — |
| Double-blind: Ustekinumab | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | Pre-dose OL Week 0 | 4.765 mcg/mL | Standard Deviation 2.1977 |
| Double-blind: Ustekinumab | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | OL Week 24 | 4.807 mcg/mL | — |
| Double-blind: Ustekinumab | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | OL Week 8 | 10.912 mcg/mL | Standard Deviation 4.5891 |
| Double-blind: Ustekinumab | Serum Concentrations of Ustekinumab in Participants Receiving Ustekinumab During Open-label Extension Phase | OL Week 40 | 3.911 mcg/mL | — |
Secondary
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.
Time frame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Population: FAS includes all randomized participants who received at least 1 dose of study intervention through double-blind period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Double-blind: Placebo | Time to Relapse of TAK According to Kerr's Criteria Through the End of Double-blind Period | 12.64 Weeks |
| Double-blind: Ustekinumab | Time to Relapse of TAK According to Kerr's Criteria Through the End of Double-blind Period | 11.14 Weeks |
Secondary
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.
Time frame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Population: FAS included all randomized participants who received at least 1 dose of study intervention through double-blind period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Double-blind: Placebo | Time to Relapse of TAK Based on Clinical Symptoms Through the End of Double-blind Period | 12.14 weeks |
| Double-blind: Ustekinumab | Time to Relapse of TAK Based on Clinical Symptoms Through the End of Double-blind Period | 4.14 weeks |
Secondary
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.
Time frame: From double-blind Week 0 up to end of double-blind period (up to 71.1 weeks)
Population: FAS includes all randomized participants who received at least 1 dose of study intervention through double-blind period. Here, '0' in the number analyzed field signifies that no participants were in relapse.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Double-blind: Placebo | Time to Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Systemic Symptoms (Objective Assessment) | 14.00 weeks |
| Double-blind: Placebo | Time to Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Systemic Symptoms (Subjective Assessment) | 12.64 weeks |
| Double-blind: Placebo | Time to Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Elevated Inflammation Markers | 13.14 weeks |
| Double-blind: Placebo | Time to Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Vascular Signs And Symptoms | 12.14 weeks |
| Double-blind: Ustekinumab | Time to Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Vascular Signs And Symptoms | 7.14 weeks |
| Double-blind: Ustekinumab | Time to Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Systemic Symptoms (Objective Assessment) | NA weeks |
| Double-blind: Ustekinumab | Time to Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Elevated Inflammation Markers | 12.14 weeks |
| Double-blind: Ustekinumab | Time to Relapse of TAK in Each of the 5 Categories (Within Protocol-defined Criteria) Through the End of Double-blind Period | Systemic Symptoms (Subjective Assessment) | 10.00 weeks |