A Phase 3 Study of the Efficacy, Safety and Pharmacokinetics of Ustekinumab as Openlabel Intravenous Induction Treatment Followed by Randomized Double-blind Subcutaneous Ustekinumab Maintenance in Pediatric Participants with Moderately to Severely Active Ulcerative Colitis
A Study of Ustekinumab in Pediatric Participants with Moderately to Severely Active Ulcerative Colitis (UC)
Nishikawa Kazuko
Janssen Pharmaceutical K.K.
3-5-2 Nishi-kanda, Chiyoda-ku, Tokyo
+81-120-183-275
DL-JANJP-JCO_TL_TSG_EMP@its.jnj.com
Medical Information Center
Janssen Pharmaceutical K.K.
3-5-2 Nishi-kanda, Chiyoda-ku, Tokyo
+81-120-183-275
DL-JANJP-JCO_TL_TSG_EMP@its.jnj.com
Recruiting
Oct. 12, 2021
Oct. 28, 2021
100
Interventional
randomized controlled trial
double blind
dose comparison control
parallel assignment
treatment purpose
- Medically stable on the basis of physical examination, medical history, and vital signs, performed at screening. Any abnormalities must be consistent with the underlying illness in the study population and this determination must be recorded in the participant's source documents and acknowledged by the investigator
- Must have had UC diagnosed prior to screening
- Have moderately to severely active UC, defined as a baseline Mayo score of 6 through 12, inclusive, with a screening Mayo endoscopy subscore greater than or equal to (>=) 2 as determined by a central review of the video of the endoscopy
- A participant who has had extensive colitis for >= 8 years, or disease limited to the left side of the colon for >= 10 years, must: a) have had a full colonoscopy to assess for the presence of dysplasia within 1 year before the first administration of study intervention or b) have a full colonoscopy with surveillance for dysplasia as the baseline endoscopy during the screening period. Results from these surveillance biopsies must be negative for dysplasia (low-grade, high-grade, or indeterminant) prior to the first administration of study intervention
- Females of childbearing potential must have a negative highly sensitiveurine pregnancy test at screening and at Week I-0 prior to study intervention administration
- Have UC limited to the rectum only or to less than (<) 20 centimeter (cm) of the colon
- Presence or history of colonic or small bowel obstruction within 6 months prior to screening, confirmed by objective radiographic or endoscopic evidence of a stricture with resulting obstruction (dilation of the colon or small bowel proximal to the stricture on barium radiograph or an inability to traverse the stricture at endoscopy)
- Have a history of latent or active granulomatous infection, histoplasmosis, or coccidioidomycosis, or have had a nontuberculous mycobacterial infection prior to screening
- Presence or history of any malignancy including presence or history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as
lymphadenopathy of unusual size or location (example, nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic areas) and monoclonal gammopathy of undetermined significance, or clinically significant hepatomegaly or splenomegaly
- Has known allergies, hypersensitivity, or intolerance to ustekinumab or its excipients
2age old over
18age old not
Both
Colitis, Ulcerative
-Ustekinumab Dose Based on BSA and Body Weight
As per BSA and body weight Ustekinumab will be administered SC and IV.
Induction Period (I):Ustekinumab
Maintenance (M) Period: Ustekinumab once every 8 Week (q8w)
Maintenance (M) Period: Ustekinumab once every 12 Week (q12w)
-Matching Placebo
Placebo will be administered subcutaneously.
Maintenance (M) Period: Ustekinumab once every 8 Week (q8w)
Maintenance (M) Period: Ustekinumab once every 12 Week (q12w)
Global:
Number of Participants with Clinical Remission at Induction Week 8 (I-8) Visit
Clinical remission is defined as Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency ubscore has not increased from induction baseline.
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability
SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product.
Number of Participants with AEs Leading to Discontinuation of Study Intervention
Number of Participants with discontinuation of study intervention due to an AE, infections, injection-site reactions, and AEs during or within 1 hour of an infusion will be reported.
Number of Participants with AEs of Special Interest (AESI) as a Measure of Safety and Tolerability
AESI of any newly identified malignancy, case of active tuberculosis (TB), or opportunistic infection ccurring after the first administration of study intervention(s) in participants will be reported.
Number of Participants with Laboratory Abnormalities
Number of participants with laboratory abnormalities related to hematology, serum chemistry, and coagulation will be reported.
Reactions Temporally Associated with an Intravenous (IV) Infusion and Subcutaneous (SC) Injection-site Reactions
Reactions temporally associated with an IV infusion (induction period) and SC injection-site reactions (maintenance period) will be reported.
Serum Concentration of Ustekinumab
Serum samples will be analyzed to determine concentrations of ustekinumab.
US Specific: Clinical Remission at M-44 for Participants who are in Clinical Response at I-8
Clinical remission at M-44 for participants who are in clinical response at I-8 will be reported. Clinical remission is defined as a Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline.
Global:
Number of Participants With Clinical Response at I-8 Visit
Clinical response is defined as decrease from baseline in the modified Mayo score by >= 30 percent (%) and >=2 points, with either a decrease from baseline in the rectal bleeding subscore of >= 1 or a rectal bleeding subscore of 0 or 1.
Number of Participants with Symptomatic Remission at I-8 Visit
Symptomatic remission is defined as Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0, where the stool frequency subscore has not increased from induction baseline.
Clinical Remission at I-8 as Assessed by the Pediatric Ulcerative Colitis Activity Index Score (PUCAI) Score
Clinical remission is defined as a PUCAI score less than (<)10.
Endoscopic Improvement at I-8 Visit
Endoscopic improvement is defined as a Mayo endoscopy subscore of 0 or <= 1 with no friability present on the endoscopy.
Histologic-endoscopic Mucosal Improvement at Week I-8
Histologic-endoscopic mucosal improvement is defined as achieving a combination of histologic (neutrophil infiltration in less than [<] 5% of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system) and endoscopic improvement (endoscopy subscore of 0 or 1 with no friability present on the endoscopy).
Number of Participants with Clinical Remission at Week 44 (M-44) Visit
Clinical remission is defined as a Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline.
Number of Participants with Symptomatic Remission at M-44 Visit
Symptomatic remission is defined as Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0, where the stool frequency subscore has not increased from induction baseline.
Clinical Remission at M-44 as Assessed by the PUCAI Score
Clinical remission is defined as a PUCAI score less than < 10.
Endoscopic Improvement at M-44 Visit
Endoscopic improvement is defined as a Mayo endoscopy subscore of 0 or <= 1 with no friability present on the endoscopy.
Corticosteroid-free Clinical Remission at Week M-44
Corticosteroid-free clinical remission is defined as a Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline; and not receiving corticosteroids for at least 90 days prior to Week M-44.
Clinical Remission at M-44 and not Receiving Corticosteroids for at Least 90 Days Prior to M-44 Among Participants who Received Corticosteroids at M-0
Clinical remission is defined as a PUCAI score less than < 10. Clinical remission at M-44 and in participants not receiving corticosteroids for at least 90 days prior to M-44 among participants who received corticosteroids at M-0 as assessed by PUCAI score will be reported.
Clinical Remission at M-44 for Participants who are in Clinical Remission at I-8
Clinical remission at M-44 for participants who are in clinical remission at I-8 will be reported. Clinical remission is defined as a Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline.
US Specific:
Number of Participants with Clinical Remission at I-8 Visit
Clinical remission is defined as Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline.
Histologic-endoscopic Mucosal Improvement at Week M-44
Histologic-endoscopic mucosal improvement is defined as achieving a combination of histologic (neutrophil infiltration in < 5% of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system) and endoscopic improvement (endoscopy subscore of 0 or 1 with no friability present on the endoscopy).
Janssen Pharaceutical K.K.
Juntendo University Hospital Institutional Review Board
3-1-3 Hongo, Bunkyo-ku, Tokyo
+81-3-5802-1584
Approval
Dec. 25, 2020
Yes
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinicaltrials/ 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
2019-004224-38
EudraCT
NCT04630028
ClinicalTrials.gov
United States Of America/Belgium/Germany/Hungary/Poland/Russian Federation/United Kingdom Of Great Britain And Northern Irela
