Clinical Trials List
Protocol NumberM15-991
NCT Number(ClinicalTrials.gov Identfier)NCT03104413
2017-12-01 - 2020-04-01
Phase III
Terminated5
ICD-10K50.90
Crohn's disease, unspecified, without complications
ICD-10K50
Crohn's disease [regional enteritis]
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
-
Trial Applicant
AbbVie
-
Sponsor
AbbVie
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Tsung-Yu Tsai Digestive System Department
- Chun-Lung Feng Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 趙德馨 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 康瑞文 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- 張世慶 Division of Colorectal Surgery
- 王煥昇 Division of Colorectal Surgery
- Hung-Hsin Lin Division of Colorectal Surgery
- 姜正愷 Division of Colorectal Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
CRO
Principal Investigator
Co-Principal Investigator
- 翁昭旼 Digestive System Department
- 謝銘鈞 Division of Hematology & Oncology
- YEN-HSUAN NI Division of Pediatrics
- SHU-CHEN WEI Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Crohn’s Disease
Objectives
The objective of Study M15-991 is to evaluate the efficacy and safety of risankizumab
versus placebo during induction therapy in subjects with moderately to severely active Crohn's disease
(CD).
Test Drug
Risankizumab(ABBV-066)
Active Ingredient
Risankizumab
Dosage Form
Vial;PFS
Dosage
Vial 300 mg/3.33 mL; Prefilled syringe 90 mg/mL
Endpoints
Efficacy:
Co-Primary Endpoints: Proportion of subjects with clinical remission at Week 12 and proportion of
subjects with endoscopic response at Week 12 (risankizumab vs placebo).
Ranked Secondary Endpoints (Risankizumab vs Placebo):
1. Proportion of subjects with enhanced clinical response at Week 4
2. Proportion of subjects with Crohn's disease activity index (CDAI) < 150 at Week 12, in subjects with
CDAI 220 to 450 at Baseline
3. Proportion of subjects with enhanced clinical response at Week 12
4. Proportion of subjects with clinical remission at Week 4
5. Proportion of subjects with enhanced clinical response and endoscopic response at Week 12
6. Proportion of subjects with endoscopic healing at Week 12
7. Change from Baseline in Crohn's Symptom Severity (CSS) at Week 12
8. Proportion of subjects with resolution of extra-intestinal manifestations (EIMs) at Week 12, in
subjects with EIMs at Baseline
9. Proportion of subjects with hospitalization through Week 12
10. Proportion of subjects with draining fistulas at Week 12 in subjects with draining fistulas at Baseline
11. Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue
(FACIT-Fatigue) at Week 12
12. Change from Baseline in SF-36 at Week 12
13. Proportion of subjects with CD-related surgeries through Week 12
For further information, including non-ranked endpoints, refer to protocol.
Co-Primary Endpoints: Proportion of subjects with clinical remission at Week 12 and proportion of
subjects with endoscopic response at Week 12 (risankizumab vs placebo).
Ranked Secondary Endpoints (Risankizumab vs Placebo):
1. Proportion of subjects with enhanced clinical response at Week 4
2. Proportion of subjects with Crohn's disease activity index (CDAI) < 150 at Week 12, in subjects with
CDAI 220 to 450 at Baseline
3. Proportion of subjects with enhanced clinical response at Week 12
4. Proportion of subjects with clinical remission at Week 4
5. Proportion of subjects with enhanced clinical response and endoscopic response at Week 12
6. Proportion of subjects with endoscopic healing at Week 12
7. Change from Baseline in Crohn's Symptom Severity (CSS) at Week 12
8. Proportion of subjects with resolution of extra-intestinal manifestations (EIMs) at Week 12, in
subjects with EIMs at Baseline
9. Proportion of subjects with hospitalization through Week 12
10. Proportion of subjects with draining fistulas at Week 12 in subjects with draining fistulas at Baseline
11. Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue
(FACIT-Fatigue) at Week 12
12. Change from Baseline in SF-36 at Week 12
13. Proportion of subjects with CD-related surgeries through Week 12
For further information, including non-ranked endpoints, refer to protocol.
Inclution Criteria
Main Inclusion:
1. Male or female aged ≥ 18 to ≤ 80 years 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. SES-CD, excluding the presence of narrowing component, ≥ 6 (or ≥ 4 for subjects with isolated
ileal disease), on an endoscopy confirmed by a central reader.
4. Average daily SF ≥ 4 and/or average daily AP score ≥ 2 at Baseline.
5. Demonstrated intolerance or inadequate response to one or more of the following biologic agents:
infliximab, adalimumab, certolizumab pegol, natalizumab, and/or vedolizumab:
Demonstration of intolerance requires no minimum dose or duration of use
Inadequate response to biologic agents defined as signs and symptoms of persistently active
disease despite a history of one or more of the following:
o At least one 6-week induction regimen of infliximab (≥ 5 mg/kg IV at Weeks 0, 2, and 6),
o 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]),
o At least one 4-week induction regimen of certolizumab pegol (400 mg SC at Weeks 0, 2,
and 4)
o At least one 6-week induction regimen of vedolizumab (300 mg IV at Weeks 0, 2, and 6)
o At least one 12-week induction regimen of natalizumab (300 mg IV every 4 weeks)
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
6. 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.
7. Subjects must be able and willing to give written informed consent and to comply with the
requirements of this study protocol.
1. Male or female aged ≥ 18 to ≤ 80 years 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. SES-CD, excluding the presence of narrowing component, ≥ 6 (or ≥ 4 for subjects with isolated
ileal disease), on an endoscopy confirmed by a central reader.
4. Average daily SF ≥ 4 and/or average daily AP score ≥ 2 at Baseline.
5. Demonstrated intolerance or inadequate response to one or more of the following biologic agents:
infliximab, adalimumab, certolizumab pegol, natalizumab, and/or vedolizumab:
Demonstration of intolerance requires no minimum dose or duration of use
Inadequate response to biologic agents defined as signs and symptoms of persistently active
disease despite a history of one or more of the following:
o At least one 6-week induction regimen of infliximab (≥ 5 mg/kg IV at Weeks 0, 2, and 6),
o 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]),
o At least one 4-week induction regimen of certolizumab pegol (400 mg SC at Weeks 0, 2,
and 4)
o At least one 6-week induction regimen of vedolizumab (300 mg IV at Weeks 0, 2, and 6)
o At least one 12-week induction regimen of natalizumab (300 mg IV every 4 weeks)
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
6. 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.
7. Subjects must be able and willing to give written informed consent and to comply with the
requirements of this study protocol.
Exclusion Criteria
Main Exclusion:
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 anti-infectives
(non-CD-related) within 14 days prior to the Baseline visit.
7. Subject who received 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 (e.g., infliximab, adalimumab, certolizumab,
natalizumab, vedolizumab) within 8 weeks prior to Baseline, or 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 p40 inhibitors (e.g., ustekinumab [Stelara]), 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 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),
impassable or fixed bowel stenosis or strictures,
symptomatic bowel strictures,
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 of Chinese hamster ovary (CHO).
23. Subjects with the following chronic or active infections:
Active, chronic, or recurrent infection that based on the Investigator's clinical assessment makes
the subject unsuitable candidate for the study,
Infection with C. difficile toxin or other intestinal pathogen during Screening,
Are infected with human immunodeficiency virus (HIV),
QuantiFERON®
-TB test or Purified Protein Derivative (PPD) skin test will be performed during
Screening. Subjects with a positive test result may participate in the study if further work up
(according to local practice/guidelines) establishes conclusively that the subject has no evidence
of active tuberculosis (subjects with active or history of active TB who have documented
completion of a full course of anti-TB therapy may be allowed to enter the study after
consultation with the AbbVie TA MD
Have active hepatitis B or hepatitis C defined as:
HBV: hepatitis B surface antigen (HBs Ag) positive (+), or detected sensitivity on the HBV
deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) qualitative test for hepatitis B
core antibody (HBc Ab) positive subjects
HCV: HCV ribonucleic acid (RNA) detectable in any subject with positive anti-HCV antibody
(HCV Ab)
24. Subject with a previous history of dysplasia of the gastrointestinal tract or found to have dysplasia,
other than completely removed low-grade dysplastic lesions, in any biopsy performed during the
Screening endoscopy.
25. Subject with a known history of lymphoproliferative disease, including lymphoma, or signs and
symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or
splenomegaly.
26. Subject with current or previous history of malignancy other than a successfully treated
non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of
the cervix.
27. Subject who has severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine,
disorder or symptoms thereof.
28. Female subjects who is pregnant, breastfeeding, or is considering becoming pregnant during the
study or for approximately 112 days after the last dose of study drug.
29. Subject who has any condition that in the opinion of the Investigator, would compromise the safety
of the subject or the quality of the data and is an unsuitable candidate for the study.
30. Screening laboratory and other analyses show any of the following abnormal results:
Aspartate transaminase (AST), alanine transaminase (ALT) > 2 × upper limit of the reference
range;
White blood cell (WBC) count < 3.0 × 109/L;
Total bilirubin ≥ 2 mg/dL; except for subjects with isolated elevation of indirect bilirubin
relating to Gilbert syndrome;
Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal
Disease (MDRD) formula < 30 ml/min/1.73 m2
.
Hemoglobin < 8 g/dL
Platelets < 100,000/µL
Positive serum pregnancy test at the Screening visit or positive urine pregnancy test at the
Baseline visit
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 anti-infectives
(non-CD-related) within 14 days prior to the Baseline visit.
7. Subject who received 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 (e.g., infliximab, adalimumab, certolizumab,
natalizumab, vedolizumab) within 8 weeks prior to Baseline, or 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 p40 inhibitors (e.g., ustekinumab [Stelara]), 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 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),
impassable or fixed bowel stenosis or strictures,
symptomatic bowel strictures,
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 of Chinese hamster ovary (CHO).
23. Subjects with the following chronic or active infections:
Active, chronic, or recurrent infection that based on the Investigator's clinical assessment makes
the subject unsuitable candidate for the study,
Infection with C. difficile toxin or other intestinal pathogen during Screening,
Are infected with human immunodeficiency virus (HIV),
QuantiFERON®
-TB test or Purified Protein Derivative (PPD) skin test will be performed during
Screening. Subjects with a positive test result may participate in the study if further work up
(according to local practice/guidelines) establishes conclusively that the subject has no evidence
of active tuberculosis (subjects with active or history of active TB who have documented
completion of a full course of anti-TB therapy may be allowed to enter the study after
consultation with the AbbVie TA MD
Have active hepatitis B or hepatitis C defined as:
HBV: hepatitis B surface antigen (HBs Ag) positive (+), or detected sensitivity on the HBV
deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) qualitative test for hepatitis B
core antibody (HBc Ab) positive subjects
HCV: HCV ribonucleic acid (RNA) detectable in any subject with positive anti-HCV antibody
(HCV Ab)
24. Subject with a previous history of dysplasia of the gastrointestinal tract or found to have dysplasia,
other than completely removed low-grade dysplastic lesions, in any biopsy performed during the
Screening endoscopy.
25. Subject with a known history of lymphoproliferative disease, including lymphoma, or signs and
symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or
splenomegaly.
26. Subject with current or previous history of malignancy other than a successfully treated
non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of
the cervix.
27. Subject who has severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine,
disorder or symptoms thereof.
28. Female subjects who is pregnant, breastfeeding, or is considering becoming pregnant during the
study or for approximately 112 days after the last dose of study drug.
29. Subject who has any condition that in the opinion of the Investigator, would compromise the safety
of the subject or the quality of the data and is an unsuitable candidate for the study.
30. Screening laboratory and other analyses show any of the following abnormal results:
Aspartate transaminase (AST), alanine transaminase (ALT) > 2 × upper limit of the reference
range;
White blood cell (WBC) count < 3.0 × 109/L;
Total bilirubin ≥ 2 mg/dL; except for subjects with isolated elevation of indirect bilirubin
relating to Gilbert syndrome;
Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal
Disease (MDRD) formula < 30 ml/min/1.73 m2
.
Hemoglobin < 8 g/dL
Platelets < 100,000/µL
Positive serum pregnancy test at the Screening visit or positive urine pregnancy test at the
Baseline visit
The Estimated Number of Participants
-
Taiwan
10 participants
-
Global
618 participants
