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 Crohn's Disease

• Register: EUCTR
• Last refreshed on: 5 January 2021
• Main ID: EUCTR2019-004225-24-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 Crohn's Disease
• 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 Crohn’s Disease - UNITI-Jr
• Target sample size: 90
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-004225-24
• 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 NV

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International NV

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. Criterion modified per Amendment 2
3.1 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, 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.

Crohn's Disease diagnosis and status
4. Have Crohn's disease or fistulizing Crohn's disease of at least 3 months duration, with active colitis, ileitis, or ileocolitis, confirmed at any time in the past by endoscopy and histology.
5. Must have moderately to severely active Crohn's disease (as defined by a baseline PCDAI score >30) AND at least one of the following:
a. An abnormal CRP (>0.3 mg/dL or 3.0 mg/L at screening)
OR
b. Fecal calprotectin of =250 mg/kg or =250 µg/g at screening
OR
c. Ileocolonoscopy with evidence of active Crohn's disease (defined as ulcerations in the ileum and/or colon) during screening into this study including at the baseline visit.

Allowed concomitant or prior medical therapies for Crohn's disease
6. Prior or current medication for Crohn's disease must include at least 1 of the following:
Have received biologic therapy for the treatment of pediatric Crohn's disease 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 the biologic therapy.
OR
Be naïve to biologic therapy (ie, have not demonstrated a history of failure to respond to or failure to tolerate a biologic therapy) and have a prior or current Crohn's disease 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, AZA, or MTX).
OR
c. History of corticosteroid dependence (ie, an inability to successfully taper corticosteroids without a return of the symptoms of Crohn's disease).
OR
d. Have required more than 3 courses of oral or IV corticosteroids in the past year.
7. Must meet concomitant medication dose stability criteria prior to the first administration of study intervention:

Corticosteroids
a. If receiving budesonide or beclomethasone dipropionate, the dose must have been stable for at least 2 weeks prior to Week I-0.
7.1 Criterion modified per Amendment 2
b. If receiving oral corticosteroids other than budesonide or beclomethasone dipropionate, the dose must be =1.5 mg/kg/da
Exclusion criteria:
Any potential participant who meets any of the following criteria will be excluded from participating in the study:

Crohn's disease diagnosis and status
1. Has complications of Crohn's disease such as symptomatic strictures or stenosis, short gut syndrome, or any other manifestation that might be anticipated to require surgery, that could preclude the use of the PCDAI to assess response to therapy or would possibly confound the ability to assess the effect of treatment with ustekinumab.
2. Currently has or is suspected to have an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks prior to baseline, or 8 weeks prior to baseline for intra-abdominal abscesses, provided that there is no anticipated need for any further surgery. Participants with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses identified.
3. Has had any kind of bowel resection within 6 months or any other intra abdominal surgery within 3 months prior to Week I-0.
4. Presence of a stoma.

Concomitant or Previous Medical Therapies Received
5. Has received any of the following prescribed medications or therapies within the specified period:
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 LY3074828), and risankizumab.
c. Has ever received thalidomide or related agents.
d. Has received natalizumab within 12 months of Week I-0.
e. 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.
f. Has received vedolizumab without appropriate washout period prior to Week I-0.
g. Has received other immunomodulatory agents (eg, 6-thioguanine [6-TG], cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil) within 8 weeks prior to Week I-0.
h. Has received anti-TNFa biologic agents without an appropriate washout period prior to Week I-0.
i. Has used any investigational intervention within 4 weeks prior to Week I-0 or within 5 half-lives of the investigational intervention, whichever is longer.
j. Has used apheresis (ie, Adacolumn apheresis, Cellsorba apheresis) within 2 weeks prior to Week I-0.
k. Have used laxatives, except preparations for endoscopy or other procedures, within 1 week prior to screening procedures.
l. Has initiated enteral nutrition therapy <3 weeks prior to the first administration of study intervention at Week I-0. (Participants who are on a stable regimen =2 weeks prior to the anticipated first administration of study intervention at Week I-0 may be considered for enrollment).
m. Has an indwelling catheter.
n. Is on total (complete) or partial (supplemental) parenteral nutrition or anticipated to require during enrollment in the study. If recently on total (complete) or partial (supplemental) parenteral nutrition, much have stopped therapy at least <3 weeks before baseline.
o. Is on rectal therapy for Crohn's disease with either 5-ASA medications or corticosteroids.
p. Is on IV steroids
q. Is on more than one antibiotic prescribed for the treatment of Crohn's disease

Infections or Predisposition to Infections
6. Have a history of latent or active granulomatous infection, including TB,

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 Crohn's Disease
MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

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)

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

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).

Main Objective: Global:
1. To evaluate the efficacy of ustekinumab dosing in inducing clinical remission in pediatric participants with moderately to severely Crohn's disease
2. To evaluate the safety profile of ustekinumab in pediatric participants with moderately to severely active Crohn's disease.
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]).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1, 3, 13 and 15 Week I-6
2, 12 and 14 Week I-8
4, 5, 16 and 17 Week M-8
6 - 11 and 18 - 22 Week M-44

Secondary end point(s): Secondary endpoints are:

Global
1. Clinical remission at Week I-6
2. Clinical response at Week I-8.
3. Clinical response at Week I-6
4. Endoscopic response at Week M-8
5. Clinical response at Week M-8

The following endpoints will be evaluated for participants who are clinical responders at Week I-8
6. Clinical remission at Week M-44
7. Endoscopic response at Week M-44
8. Clinical response at Week M-44
9. Corticosteriod-free clinical remission at Week M-44
10. Corticosteriod-free clinical response at Week M-44
11. Durable clinical remission at Week M-44

US-specific
12. Clinical Remission at Week I-8
13. Clinical Remission at Week I-6
14. Clinical Response at Week I-8
15. Clinical response at Week I-6.
16. Endoscopic response at Week M-8.*
17. Clinical response at Week M-8.*

The following endpoints will be evaluated for participants who are clinical responders at Week I-8:
18. Endoscopic response at Week M-44.
19. Clinical response at Week M-44.
20. Corticosteroid-free clinical remission at Week M-44.
21. Corticosteroid-free clinical response at Week M-44.
22. Durable clinical remission at Week M-44.

Secondary ID(s)

CNTO1275CRD3004

2019-004225-24-DE

Source(s) of Monetary Support

Janssen Research & Development, LLC