A Clinical Study of the Efficacy, Safety and Pharmacokinetics of Ustekinumab as Intravenous Induction Treatment Followed by Subcutaneous Ustekinumab Maintenance in Pediatric Participants with Moderately to Severely Active Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 5 January 2021
• Main ID: EUCTR2019-004224-38-GB
• Date of registration: 25/11/2020
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: A Clinical Study of the Efficacy, Safety and Pharmacokinetics of Ustekinumab as Intravenous Induction Treatment Followed by Subcutaneous Ustekinumab Maintenance in Pediatric Participants with Moderately to Severely Active Ulcerative Colitis
• Scientific title: A Phase 3 Study of the Efficacy, Safety and Pharmacokinetics of Ustekinumab as Open-label Intravenous Induction Treatment Followed by Randomized Double-blind Subcutaneous Ustekinumab Maintenance in Pediatric Participants with Moderately to Severely Active Ulcerative Colitis - UNIFI-Jr
• Target sample size: 90
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-004224-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Maintenance Period: Randomized, double-blind, parallel group 2-arm study If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Germany, Hungary, Japan, Poland, Russian Federation, United Kingdom, United States

Contacts

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International N.V.

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International N.V.

Key inclusion & exclusion criteria

Inclusion criteria:
Each potential participant must satisfy all of the following criteria to be enrolled in the study:

General
1. 2 to <18 years of age, inclusive (at the time of the first administration of study intervention at Week I-0) with a body weight =10 kg.
2. 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.
3. Medically stable on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel including liver enzymes, other specific tests, blood coagulation, or hematology are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and acknowledged by the investigator.

UC diagnosis and status
4. Must have had UC diagnosed for at least 1 month prior to screening.
5. Must have biopsy confirmation that is consistent with a diagnosis of UC (eg, crypt distortion, crypt abscess, and goblet cell depletion).
6. Have moderately to severely active UC, defined as a baseline Mayo score of 6 through 12, inclusive, with a screening Mayo endoscopy subscore =2 as determined by a central review of the video of the endoscopy.

Allowed concomitant or previous medical therapies for UC
7. Prior or current medication for UC must include at least one of the following:
Have received biologic therapy (ie, TNFa antagonist or vedolizumab) for the treatment of pediatric UC and have had an appropriate washout duration prior to first administration of study intervention and have a documented history of failure to respond to or not tolerate treatment;
OR
Be naïve to biologic therapy or have not demonstrated a history of failure to respond to, or tolerate a biologic therapy and have a prior or current UC medication history that includes at least 1 of the following:
a. Inadequate response to or failure to tolerate current treatment with oral or IV corticosteroids or immunomodulators (6-MP, AZA, or MTX)
OR
b. History of failure to respond to, or tolerate, at least 1 of the following therapies: oral or IV corticosteroids or immunomodulators (6-MP or AZA or MTX)
OR
c. History of corticosteroid dependence (ie, an inability to successfully taper corticosteroids without a return of the symptoms of UC)
OR
d. Have required more than 3 courses of oral or IV corticosteroids in the past year.
8. Must meet concomitant medication criteria prior to the first administration of study intervention:

Corticosteroids
a. If receiving budesonide or beclomethasone dipropionate, the dose must have been stable or discontinued for at least 2 weeks prior to Week I-0.
b. If receiving oral corticosteroids, other than budesonide or beclomethasone dipropionate, the dose must be =1.5 mg/kg/day prednisone or its equivalent (up to 40 mg/day) and must have been stable or discontinued for at least 2 weeks prior to Week I-0.
c. IV or rectal corticosteroids must have been discontinued for at least 2 weeks prior to Week I-0.

5-Aminosalicylates, MTX, 6-MP, and AZA Compounds
d. If receiving oral or rectal 5-ASA compound
Exclusion criteria:
Any potential participant who meets any of the following criteria will be excluded from participating in the study:

UC Diagnosis and Status
1. Have severe, extensive colitis as evidenced by:
a. Investigator judgment that the participant is likely to require a colectomy within 12 weeks of Week I-0.
OR
b. Symptom complex at screening or Week I-0 visit that includes at least 4 of the following:
• Diarrhea with =6 bowel movements/day with macroscopic blood in stool
• Focal severe or rebound abdominal tenderness
• Persistent fever (=37.5°C) for more than 5 days
• Persistent tachycardia for more than 5 days
• Anemia (hemoglobin <8.5 g/dL)
2. Have UC limited to the rectum only or to <20 cm of the colon.
3. Presence of a stoma.
4. Presence or history of a fistula.
5. Have severe, fixed symptomatic stenosis of the large or small intestine.
6. Require, or required within the 2 months prior to screening, surgery for active GI bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage, or other conditions possibly confounding the evaluation of benefit from study intervention treatment.
7. 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 strictureon barium radiograph or an inability to traverse the stricture at endoscopy).
8. History of extensive colonic resection (eg, less than 30 cm of colon remaining) that would prevent adequate evaluation of the effect of study intervention on clinical disease activity.
9. Presence on screening endoscopy of adenomatous colonic polyps, if not removed prior to study entry, or history of adenomatous colonic polyps that were not removed.
10. Have evidence of Crohn’s disease:
a. Small intestinal or ileal disease by upper GI small bowel follow-through, ileocolonoscopy with histology, video capsule endoscopy, or magnetic resonance enterography
b. Noncaseating and non-mucin granulomas that are suggestive of a diagnosis of Crohn’s disease on colonoscopy
c. Skip lesions on colonoscopy including absolute rectal sparing, with a normal rectum both endoscopically and histologically
d. Perianal disease

Concomitant or previous medical therapies received
11. Have received the following concomitant or previous medical therapies:
a. Has ever received ustekinumab or a biologic agent targeting IL-12/23 or IL-23, including but not limited to briakinumab, brazikumab, guselkumab, mirikizumab (formerly LY-3074828), and risankizumab.
b. Has ever received thalidomide or related agents.
c. Has received natalizumab within 12 months of Week I-0.
d. Has received agents that deplete B or T cells (eg, rituximab, alemtuzumab, or visilizumab) within 12 months of Week I-0 or continue to manifest depletion of B or T cells more than 12 months after completion of therapy with lymphocyte depleting agents.
e. Has received vedolizumab without an appropriate washout period prior to Week I-0.
f. Has received other oral immunomodulatory agents (eg, 6-thioguanine [6-TG], cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil [MMF]) within 8 weeks prior to Week I-0.
g. Has received anti-TNFa biologic agents without an appropriate washout period prior to Week I-0.
h. Has used any investigational intervention within 4 weeks prior to Week I-0 or within 5 half-liv

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Moderately to Severely Active Ulcerative Colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Trade Name: STELARA®
Product Name: Ustekinumab
Product Code: CNTO1275
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Ustekinumab
CAS Number: 815610-63-0
Current Sponsor code: CNTO1275
Other descriptive name: USTEKINUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: STELARA®
Product Name: Ustekinumab
Product Code: CNTO1275
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Ustekinumab
CAS Number: 815610-63-0
Current Sponsor code: CNTO1275
Other descriptive name: USTEKINUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 90-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: STELARA®
Product Name: Ustekinumab
Product Code: CNTO1275
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Ustekinumab
CAS Number: 815610-63-0
Current Sponsor code: CNTO1275
Other descriptive name: USTEKINUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 90-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Global
1. Clinical remission at Induction Week 8 (Week I-8).

US-specific
2. Clinical remission at Maintenance Week (Week M-44).

Secondary Objective: 1. To evaluate the efficacy of IV ustekinumab during the induction period.
2. To evaluate the efficacy of SC ustekinumab during the maintenance period among participants who were in clinical response in induction.

Main Objective: Global:
1. To evaluate the efficacy of ustekinumab dosing in inducing clinical remission in pediatric participants with moderately to severely active UC.
2. To evaluate the safety profile of ustekinumab in pediatric participants with moderately to severely active UC.
3. To evaluate ustekinumab exposure (PK).

US specific:
4. To evaluate the efficacy of ustekinumab dosing in maintaining clinical remission among participants who were in clinical response in induction.
5. To evaluate the safety profile of ustekinumab.
6. To evaluate ustekinumab exposure (pharmacokinetics [PK]).

Timepoint(s) of evaluation of this end point: 1. Week I-8
2. Week M-44

Secondary Outcome(s)

Secondary end point(s): Secondary endpoints are:

Global
1. Clinical response at Week I-8.
2. Symptomatic remission at Week I-8.
3. Clinical remission at Week I-8 as assessed by the Pediatric Ulcerative Colitis Activity Index (PUCAI) score.
4. Endoscopic improvement at Week I-8.
5. Clinical remission at Maintenance Week (Week M-44.)
6. Symptomatic remission at Week M-44.
7. Clinical remission at Week M-44 as assessed by the PUCAI score.
8. Endoscopic improvement at Week M-44.
9. Clinical remission at Week M-44 and not receiving corticosteroids for at least 90 days prior to Week M-44 among participants who received corticosteroids at Week M-0.
10. Clinical remission at Week M-44 for participants who are in clinical remission at Week I-8.

US-specific
11. Clinical remission at Induction Week 8 (Week I-8).
12. Clinical response at Week I-8.
13. Symptomatic remission at Week I-8.
14. Clinical remission at Week I-8 as assessed by the PUCAI score.
15. Endoscopic improvement at Week I-8.
16. Symptomatic remission at Week M-44.
17. Clinical remission at Week M-44 as assessed by the PUCAI score.
18. Endoscopic improvement at Week M-44.
19. Clinical remission at Week M-44 and not receiving corticosteroids for at least 90 days prior to Week M-44 among participants who received corticosteroids at Week M-0.
20. Clinical remission at Week M-44 for participants who are in clinical remission at Week I-8.

Timepoint(s) of evaluation of this end point: 1 to 4. and 11 to 15. Week I-8
5 to 10. and 16 to 20. Week M-44

Secondary ID(s)

2019-004224-38-DE

CNTO1275PUC3001

Source(s) of Monetary Support

Janssen Research & Development, LLC