This is an open-label, single-arm, phase 4 study to assess the safety and efficacy of mirikizumab in approximately 60 participants with stricturing CD.
This is an open-label, single-arm, phase 4 study to assess the safety and efficacy of mirikizumab in approximately 60 participants with stricturing CD. This study will enroll adults (≥18 years of age) with a diagnosis of ileal or ileocolonic CD based upon radiologic, clinical, endoscopic, and histologic evidence with tolerable obstructive stricture symptoms. Participants will be recruited from approximately 15 sites in 2 countries (United States and Canada). This study consists of 3 study periods (screening period, open-label treatment period, and safety follow-up). After signing informed consent, potential study participants will be screened over a 5-week screening period, including MRE and ileocolonoscopy to confirm the presence of inflammatory strictures. Eligible participants will receive 900 mg mirikizumab IV Q4W to Week 12 and then 300 mg mirikizumab SC Q4W to Week 24. During screening and Week 24 visits, participants will undergo MRE for blinded MRE disease activity assessment with the MaRIA score and assessment of stricture features. At the same time points, ileocolonoscopy with biopsy collection (2 from the ileum, 2 from the rectum, and 2 from each colonic segment \[ascending, transverse, descending, and sigmoid\]; 12 biopsies total) will be performed for blinded endoscopic and histopathologic disease activity assessments with the SES-CD and RHI, respectively. Throughout the study, participants will undergo routine safety assessments at clinic visits, which will include physical examination, vital signs, clinical laboratory assessment, and recording of SAEs. At specified time points throughout the study, participants will complete a 7 day paper study diary consisting of patient reported items of the CDAI, UNRS, PGI-C, PGI-S, and the S-PRO. Blood samples will be collected at Weeks 12 and 24 for safety laboratory and CRP assessments. Stool samples will be collected at baseline and Week 24 for assessing FCP levels. The SIBDQ will be completed in-clinic at screening and Week 24. Participants will undergo a Safety Follow-up Visit 4 weeks after the last dose of study treatment for safety assessments and recording of SAEs, severe liver injury (ALT or AST ≥ 3 × ULN), serious infections, and CD-related complications. The safety follow-up visit can be performed by telephone, unless the participant has any ongoing AEs that require follow-up assessment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Mirikizumab is an IL-23 antagonist.
To evaluate the efficacy of mirikizumab in inducing a radiologic response in participants with inflammatory stricturing CD
Achievement of radiologic response (defined by a ≥ 50% improvement in stricture length and no worsening of prestenotic small bowel diameter OR a ≥ 50% improvement in prestenotic small bowel diameter and no worsening of stricture length)
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in S PRO score
Time frame: At week 4
To evaluate the efficacy of mirikizumab in health-related quality of life in participants with inflammatory stricturing CD
Change from baseline in S PRO score
Time frame: At week 4
To evaluate the efficacy of mirikizumab in radiologic disease activity in participants with inflammatory stricturing CD
Change from baseline in S PRO score
Time frame: At week 4
To evaluate the efficacy of mirikizumab in endoscopic disease activity in participants with inflammatory stricturing CD
Change from baseline in S PRO score
Time frame: At week 4
To evaluate the efficacy of mirikizumab in histologic disease activity in participants with inflammatory stricturing CD
Change from baseline in S PRO score
Time frame: At week 4
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
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Change from baseline in S PRO score
Time frame: At week 8
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change in baseline in S PRO score
Time frame: At week 12
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in S PRO score
Time frame: At week 16
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in S PRO score
Time frame: At week 20
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in S PRO score
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in CDAI score
Time frame: At week 12
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in CDAI score
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in PRO2 Score
Time frame: At week 12
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in PRO2 score
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in HBI score
Time frame: At week 12
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in HBI score
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Achievement of endoscopic response (defined by ≥ 50% reduction from baseline in SES-CD score) AND radiographic improvement (defined by a ≥ 25% improvement from baseline in stricture MaRIA score)
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Achievement of endoscopic response (defined by ≥ 50% reduction from baseline in SES-CD score)
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in SIBDQ score
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in UNRS score
Time frame: At week 12
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in UNRS score
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in RHI score
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Achievement of histological response (defined by a ≥ 50% reduction from baseline in RHI score)
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Achievement of CRP response (defined by ≥ 50% reduction from baseline in CRP levels)
Time frame: At week 12
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Achievement of CRP response (defined by ≥ 50% reduction from baseline in CRP levels)
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in CRP level
Time frame: At week 12
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in CRP level
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Achievement of FCP response (defined by ≥ 50% reduction from baseline in FCP level)
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in FCP level
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in PGI-S score
Time frame: At week 4
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in PGI-S score
Time frame: At week 8
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in PGI-S score
Time frame: At week 12
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in PGI-S score
Time frame: At week 16
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in PGI-S score
Time frame: At week 20
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
Change from baseline in PGI-S score
Time frame: At week 24
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
PGI-S score
Time frame: At week 4
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
PGI-S score
Time frame: At week 8
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
PGI-S score
Time frame: At week 12
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
PGI-S score
Time frame: At week 16
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
PGI-S score
Time frame: At week 20
To evaluate the efficacy of mirikizumab in improving symptoms in participants with inflammatory stricturing CD
PGI-S score
Time frame: At week 24
To evaluate the safety of mirikizumab in participants with stricturing CD
Occurrence of SAEs, severe liver injury (ALT or AST ≥ 3 × ULN), and serious infections
Time frame: Through end of safety follow-up
To evaluate the safety of mirikizumab in participants with stricturing CD
CD-related complications
Time frame: Through end of safety follow-up defined as a composite of (1) CD-related surgery, (2) CD-related hospitalization, (3) CD-medication-related complication, and (4) rescue therapy for a documented CD-related flare