A Multicenter, Randomized, Double-Blind, Placebo-Controlled Induction Study to Assess the Efficacy and Safety of Risankizumab in Subjects with Moderately to Severely Active Crohn's Disease Who Failed Prior Biologic Treatment



Short title: M15-991

Investigated disease: M. Crohn

Principal Investigator: Dr. med. Anja Schirbel


Clinic, Institute: Medizinische Klinik m.S. Hepatologie und Gastroenterologie CCM - Leitung

Patient (diseased)
Age: 18 - 80
Gender: All

Status: Participants wanted
Last change: 26.09.2020

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Study Description

Title

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Induction Study to Assess the Efficacy and Safety of Risankizumab in Subjects with Moderately to Severely Active Crohn's Disease Who Failed Prior Biologic Treatment

Short title

M15-991

EudraCT-No.

2016-003190-17

General Short Description

"Multizentrische, randomisierte, doppelblinde, placebokontrollierte Induktionsstudie zur Beurteilung der
Wirksamkeit und Sicherheit von Risankizumab bei Patienten mit mittelschwerem bis schwerem aktivem
Morbus Crohn, die nicht auf die vorherige Biologika-Behandlung angesprochen haben"

Scientific Short Description

A Multicenter, Randomized, Double-Blind,
Placebo-Controlled Induction Study to Assess the
Efficacy and Safety of Risankizumab in Subjects
with Moderately to Severely Active Crohn's Disease
Who Failed Prior Biologic Treatment

Investigated Disease, Health Issue

ICD-Code
  • K50 - Crohn-Krankheit [Enteritis regionalis] [Morbus Crohn]

Inclusion Criteria

Age

18 - 80

Gender

All

Additional Inclusion Criteria

Male or female aged ≥ 18 to ≤ 80 years, or minimum age of adult consent
according to local regulations, at the Baseline visit. Where locally permissible,
subjects 16 to < 18 years of age who meet the definition of Tanner stage 5 for
development (refer to Appendix I) at the Baseline Visit (sites will be notified when
adolescents may enroll).
2. Confirmed diagnosis of CD for at least 3 months prior to Baseline. Appropriate
documentation of biopsy results consistent with the diagnosis of CD, in the
assessment of the Investigator, must be available.
3. Crohn's disease activity index (CDAI) score 220 – 450 at Baseline.
4. Endoscopic evidence of mucosal inflammation as documented by the SES-CD of
≥ 3. All eligible scores exclude the presence of narrowing component and are
confirmed by a central reader. (Once cap of no more than 58 subjects is reached,
enrollment criterion will be an SES-CD of ≥ 6 for ileocolonic or colonic disease or
SES-CD of ≥ 4 for isolated ileal disease.)
5. Average daily SF ≥ 4 and/or average daily AP score ≥ 2 at Baseline.
6. Demonstrated intolerance or inadequate response to one or more of the following
biologic agents as defined below: infliximab, adalimumab, certolizumab pegol,
natalizumab, vedolizumab and/or ustekinumab:
● Demonstration of intolerance requires no minimum dose or duration of use
● Inadequate response to biologic agents defined as signs and symptoms of
persistently (in the opinion of the Investigator) active disease despite a history
of one or more of the following:
○ At least one 6-week induction regimen of infliximab (≥ 5 mg/kg IV at
Weeks 0, 2, and 6),
○ At least one 4-week induction regimen of adalimumab (one 160 mg SC
dose at Week 0, followed by one 80 mg SC dose at Week 2 [or one 80 mg
SC dose at Week 0, followed by one 40 mg SC dose at Week 2, in
countries where this dosing regimen is approved]),
○ At least one 4-week induction regimen of certolizumab pegol (400 mg SC
at Weeks 0, 2, and 4)
○ At least one 6-week induction regimen of vedolizumab (300 mg IV at
Weeks 0, 2, and 6),
○ At least one 12-week induction regimen of natalizumab (300 mg IV every
4 weeks)
○ At least one 8-week induction regimen of ustekinumab [260 mg (≤ 55 kg)
or 390 mg (> 55 to ≤ 85 kg) or 520 mg (> 85 kg) IV, followed by 90 mg
SC at Week 8] (Once cap of no more than 20% ustekinumab exposed
subjects is reached, subjects with prior ustekinumab exposure will not be
allowed to enroll.)
● Recurrence of symptoms during scheduled maintenance dosing following prior
clinical benefit of the above biologic agents
● Note: Subjects who discontinued biologic agents for reasons other than
inadequate response as defined above or intolerance (e.g, change of insurance)
are not eligible to enroll
7. If female, subject must meet the criteria as stated in Section 5.2.4 of this protocol
Contraception Recommendations. Females of childbearing potential must have a
negative serum pregnancy test result during Screening, and a negative urine
pregnancy at Baseline. Females of non-childbearing potential (either
postmenopausal or permanently surgically sterile as defined in Section 5.2.4)
during Screening do not require pregnancy testing at Baseline.
Note: Subjects with borderline serum pregnancy test at Screening must have a
serum pregnancy test ≥ 3 days later to document continued lack of a positive
result.
8. Subject must be able and willing to give written informed consent and to comply
with the requirements of this study protocol.

Exclusion Criteria

1. Subject with a current diagnosis of ulcerative colitis or indeterminate colitis.
Concomitant Medications and Treatments
2. Subject on CD-related antibiotics who has not been on stable doses for greater
than, or discontinued within, 14 days prior to Baseline.
3. Subject on oral aminosalicylates who has not been on stable doses for greater than,
or discontinued within, at least 14 days prior to Baseline.
4. Subject taking oral corticosteroids:
● Budesonide > 9 mg/day
● Beclomethasone > 5 mg/day
● Prednisone or equivalent > 20 mg/day
● Or has not been on the current course for ≥ 14 days prior to Baseline and on a
stable dose for ≥ 7 days prior to Baseline
5. Subject on immunomodulators (AZA, 6-MP, MTX) who:
● Has not been on the current course for ≥ 42 days prior to Baseline, and
● Has not been on a stable dose for ≥ 35 days prior to Baseline
Medications and Treatments During the Screening Period
6. Subject who received IV anti-infectives within 35 days prior to Baseline visit or
oral/intramuscular anti-infectives (non-CD-related) within 14 days prior to the
Baseline visit. This does not apply to TB prophylaxis.
7. Subject who received exclusive enteral nutrition or any parenteral nutrition within
35 days prior to Baseline.
8. Subject who received any live bacterial or viral vaccination within 30 days prior to
Screening or during the Screening Period.
9. Subject who received cyclosporine, tacrolimus, or mycophenolate mofetil within
35 days prior to Baseline.
10. Subject who received fecal microbial transplantation within 35 days prior to
Baseline.
Prior Medications and Treatments
11. Subject who received any:
● approved biologic agent: infliximab, adalimumab, certolizumab, vedolizumab,
natalizumab within 8 weeks prior to Baseline or ustekinumab within 12 weeks
prior to Baseline
Note: If there is proper documentation of an undetectable drug level measured
by a commercially available assay for any of the approved biologics above,
there is no minimum washout prior to Baseline.
● any investigational biologic or other agent or procedure within 35 days or
5 half-lives prior to Baseline, whichever is longer.
12. Subject with prior exposure to p19 inhibitors (e.g, risankizumab).
13. Subject has been taking combination of two or more of the following: oral
budesonide, or oral beclomethasone and/or oral prednisone (or equivalent)
simultaneously, with the exception of inhalers, within 14 days prior to Screening or
during the Screening period.
14. Subject who received IV/intramuscular corticosteroids within 14 days prior to
Screening or during the Screening period.
15. Subject who received therapeutic enema or suppository, other than required for
endoscopy, within 14 days prior to endoscopy used for Screening or during the
Screening period.
16. Subject who received apheresis (e.g, Adacolumn apheresis) ≤ 60 days prior to
Screening or during the Screening period.
17. Subject who has concomitant cannabis use either recreational or for medical
reasons within 14 days of Baseline or any history of clinically significant drug, or
alcohol abuse in the last 12 months.
CD Related
18. Subject with currently known complications of CD such as:
● abscess (abdominal or perianal),
● symptomatic bowel strictures,
● > 2 missing segments of the following 5 segments: terminal ileum, right
colon, transverse colon, sigmoid and left colon, and rectum
● fulminant colitis,
● toxic megacolon,
● or any other manifestation that might require surgery while enrolled in the
study.
19. Subject with ostomy or ileoanal pouch.
20. Subject diagnosed with short gut or short bowel syndrome.
21. Subject with surgical bowel resection within the past 3 months prior to Baseline, or
a history of ≥ 3 bowel resections.
Safety
22. Subject who has a known hypersensitivity to risankizumab or the excipients of any
of the study drugs or the ingredients

Characteristics

Studytype

Interventional

Studyphase

3

Contact

Contact for Study Participants


Frau Marika Saegebarth

+49 30 450 614 096

marika.saegebarth(at)charite.de

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