A Study to Evaluate Whether Healing all Bowel Wall Layers is a Superior Treatment Target in Patients with Active Crohn’s Disease (CD).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alimentiv Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

31 Jul 2024 → ongoing

Decision date (initial)

2024-07-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Takeda Development Center Americas, Inc.

External identifiers

EU CT number

2023-509096-16-00

ClinicalTrials.gov

NCT06257706

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

To demonstrate that treating to achieve a target of corticosteroid-free TMH + IUS outcomes clinical remission + biomarker remission is superior to a target of corticosteroid-free clinical remission + biomarker remission after 48 weeks

Secondary objectives 10

1. To compare composite disease outcomes in participants treated with different treat-to-target strategies for 48 weeks
2. To compare clinical outcomes in participants treated with different treat-to-target strategies for 48 weeks
3. To compare endoscopic outcomes in participants treated with different treat-to-target strategies for 48 weeks
4. To compare IUS outcomes in participants treated with different treat-to-target strategies for 48 weeks
5. To evaluate kinetics of IUS outcomes in participants with moderate to severe CD treated with vedolizumab (in participants randomized to a treatment target of IUS outcomes + clinical remission + biomarker remission)
6. To compare histologic outcomes in participants treated with different treat-to-target strategies for 48 weeks
7. To compare biomarker outcomes in participants treated with different treat-to-target strategies for 48 weeks
8. To compare patient-reported outcomes in participants treated with different treat-to-target strategies for 48 weeks
9. To compare longer-term outcomes in participants treated with different treat-to-target strategies for 48 weeks
10. To compare safety in participants treated with different treat-to-target strategies for 48 weeks

Conditions and MedDRA coding

Moderately to Severely Active Crohn’s Disease

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Adults aged 18 to 80 years, inclusive, at the time of consent;
2. Moderately to severely active CD at baseline defined by a CDAI score of 220 to 450 inclusive and SES-CD, excluding the presence of narrowing component, ≥6 (or ≥4 for participants with isolated ileal disease);
3. BWT on IUS of >4.0 mm in the terminal ileum or any colonic segment (excluding the rectum) as assessed by the mean of 2 longitudinal and 2 cross-sectional measurements of the same segment;
4. Biologic-naïve or have previous exposure (within the last 5 years of the screening date) to no more than 1 advanced therapeutic compound (approved biologic or small molecule drug) for the treatment of their CD. Note: only approximately 15% to 30% of the enrolled population will have had prior exposure to an advanced therapeutic;
5. Participants may continue stable dose (initiated at least 4 weeks prior to Screening) of 5-ASA for CD;
6. Persons of childbearing potential must have a negative serum pregnancy test prior to randomization and must use a highly effective method of contraception throughout the study. Females unable to bear children must have documentation of such in the source records;
7. Able to participate fully in all aspects of this clinical trial;
8. Written informed consent must be obtained and documented

Exclusion criteria 26

1. Current or previous treatment with vedolizumab, etrolizumab, or natalizumab;
2. Previously exposed to 2 or more compounds or classes of an advanced therapeutic compound (approved biologic or small molecule drug) for the treatment of their CD;
3. Change to oral corticosteroid therapy dosing within 2 weeks prior to randomization or a corticosteroid dose of >40 mg of prednisone or equivalent at randomization;
4. Only have inflammation proximal to the terminal ileum that cannot be reached by ileocolonoscopy;
5. Have a CD complication, such as symptomatic strictures in the small bowel with >3 cm prestenotic dilatation on any imaging modality, requiring procedural intervention;
6. Previous extensive colonic resection or missing >2 segments out of 5 (terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum), ileorectal anastomosis, or a proctocolectomy
7. Ostomy or ileoanal pouch;
8. Short bowel syndrome;
9. Fibrotic-only stricture in the ileum or colon without evidence of active inflammation (in the investigator’s judgment), including any impassable stenosis
10. Abscess >2 cm, detected by IUS or endoscopy; participants with draining fistulas are not excluded;
11. Serious underlying disease other than CD that, in the opinion of the investigator, may interfere with the participant’s ability to participate fully in the study or would compromise participant safety;
12. Positive stool test for Clostridioides difficile infection (as demonstrated by positive toxin);
13. Known HIV or hepatitis B or C infection. If a negative test result is available in the 12 months prior to randomization, retesting is not required;
14. Known active or latent tuberculosis (TB); if a negative test result is available in the 12 months prior to randomization, confirmatory testing (per standard of care) is not required before randomization;
15. Other systemic or opportunistic infection (including cytomegalovirus), any other clinically significant extraintestinal infection, or recurring infection within 6 months of randomization;
16. Has active cerebral/meningeal disease, signs, symptoms, or any history of progressive multifocal leukoencephalopathy (PML) prior to randomization;
17. Hypersensitivity, allergy, or intolerance to any excipient of vedolizumab or any other contraindication to vedolizumab;
18. Active severe infection such as sepsis, cytomegalovirus, listeriosis, or opportunistic infection.
19. Unwillingness to withhold protocol-prohibited medications during the trial;
20. Concurrent or previous participation in another clinical trial and received any investigational therapy within 30 days prior to randomization;
21. History of alcohol or drug abuse that in the opinion of the investigator may interfere with the participant’s ability to comply with the study procedures;
22. Prior enrolment in the current study and had received study treatment;
23. Pregnant, lactating, or intending to become pregnant/impregnate a partner before, during, or within 18 weeks after the last dose; or intending to donate ova or sperm during such time period;
24. Vaccination with a live or live-attenuated vaccine within 4 weeks prior to randomization, or planned vaccination with a live or live-attenuated vaccine during participation in the study;
25. Any person performing mandatory military service, deprived of liberty, in a residential care setting, or any person who, due to a judicial decision, cannot take part in clinical studies;
26. The person is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Corticosteroid-free endoscopic remission at Week 48

Secondary endpoints 10

1. Corticosteroid-free TMH + endoscopic remission + clinical remission at Week 48; Corticosteroid-free IUS response + endoscopic remission + clinical remission at Week 48; Corticosteroid-free endoscopic remission + clinical remission at Week 48; Corticosteroid-free endoscopic response + clinical response at Week 48
2. Corticosteroid-free clinical remission at Weeks 14, 22, and 48; Corticosteroid-free clinical response at Weeks 14, 22, and 48; CDAI total score and corresponding change from baseline during follow-up (Weeks 6, 14, 22, 30, 38, and 48)
3. Corticosteroid-free endoscopic response at Week 48; SES-CD total score and corresponding change from baseline to Week 48
4. TMH at Week 48; IUS response at Week 48; BWT and corresponding change from baseline at Week 48; CDS and corresponding change from baseline at Week 48; International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) (per segment as well as total) and corresponding change from baseline at Week 48
5. TMH at Weeks 14, 22, 30, 38, and 48; IUS response at Weeks 14, 22, 30, 38, and 48; BWT and corresponding change from baseline at Weeks 14, 22, 30, 38, and 48; CDS and corresponding change from baseline at Weeks 14, 22, 30, 38, and 48; IBUS-SAS and corresponding change from baseline at Weeks 14, 22, 30, 38, and 48
6. Histologic remission at Week 48; Histologic response at Week 48
7. Biomarker remission at Week 48; Biomarker response at Week 48; CRP response during follow-up (Weeks 6, 14, 22, 30, 38, and 48); FCal response during follow-up (Weeks 6, 14, 22, 30, 38, and 48); CRP and FCal and their corresponding changes from baseline during follow-up (Weeks 6, 14, 22, 30, 38, and 48)
8. 2-item Patient-Reported Outcome (PRO 2) score, Symptoms and Impacts Questionnaire for CD (SIQ-CD) score, and Urgency Numerical Rating Score (NRS) and their corresponding changes from baseline during follow-up (Weeks 6, 14, 22, 30, 38, and 48); Inflammatory Bowel Disease Questionnaire (IBDQ) score and corresponding changes from baseline during follow-up (Weeks 30 and 48)
9. Time to CD-related complication from randomization through Week 96.; Time to each component of CD-related complication; Switched to an alternate biologic (yes/no) by Week 48 and Week 96; Endpoints related to CDAI, CRP, FCal, and patient-reported measures (as specified above) at Weeks 64, 80, and 96.
10. Exposure-adjusted incidence rates of serious adverse events (SAEs), all adverse events (AEs), and AEs of special interest (AESIs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alimentiv Inc.

Sponsor organisation

Alimentiv Inc.

Address

800 Collip Circle Suite 104

City

London

Postcode

N6G 4X8

Country

Canada

Scientific contact point

Organisation

Alimentiv Inc.

Contact name

PM Group

Public contact point

Organisation

Alimentiv Inc.

Contact name

PM Group

Third parties 5

Locations

8 EU/EEA countries · 42 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 208 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications