Efficacy and Safety of Obefazimod in Subjects With Moderately to Severely Active Crohn's Disease ( ENHANCE-CD )

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Abivax

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

27 Jan 2025 → ongoing

Decision date (initial)

2025-01-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ABIVAX 7-11 Blvd. Haussmann 75009 Paris France

External identifiers

EU CT number

2023-508234-34-00

ClinicalTrials.gov

NCT06456593

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

For Induction and Maintenance phase:
to evaluate the efficacy of obefazimod compared to placebo as induction and maintenance therapy in subjects with moderately to severely active CD after inadequate response (no response, loss of response, or intolerance) to conventional therapies and/or advanced therapies.
For Extension Phase:
to evaluate the safety and tolerability of obefazimod in subjects who are enrolled in the Extension Phase.

Secondary objectives 2

1. Safety objective: to assess the safety and tolerability of obefazimod during Induction and maintenance treatment phases
2. For induction and Maintenance Phase, PK objective: to assess concentration of obefazimod and its metabolites in subjects with moderately to severely active CD.

Conditions and MedDRA coding

Crohn's disease

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003196-PIP01-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male or female (at birth) 18 to 75 years old.
2. Subjects must understand, sign and date the written voluntary informed consent form and be able and willing to comply with study visits and procedures as per protocol.
3. Confirmed and documented diagnosis of CD based on endoscopy and histology reports. For subjects with no documented diagnosis, the diagnosis must be confirmed at the screening on the local endoscopy and histology reports (with local biopsies).
4. Moderately to severely active CD as defined by 220 ≤ CDAI ≤ 450. and SES-CD ≥ 6 for ileocolonic or colonic disease or SES-CD ≥ 4 for isolated ileal disease (per central reading).
5. Documented inadequate response (defined as lack of response or loss of response or intolerance) to at least one of the following treatments: corticosteroids, immunosuppressants, biologic or biosimilar therapies, janus kinase inhibitors and/or new drugs approved for the treatment of CD during the study (note: failure to only 5- ASA is not accepted).
6. Women of childbearing potential (WOCBP) subjects and male subjects with WOCBP partner must agree to comply with contraception requirements as stated in this protocol.
7. Subject should be affiliated to a health insurance policy whenever required by a participating country or state.

Exclusion criteria 24

1. WOCBP subject who is pregnant or breast-feeding at screening, or intends to become pregnant during the study; or male subject with WOCBP partner who intends to be pregnant during the study.
2. Current diagnosis of ulcerative colitis or indeterminate colitis.
3. CD without ileal and/or colonic involvement.
4. Untreated active external or perianal fistula or abscess. Stable fistula without abscess and with minimal or low drainage may be enrolled.
5. Symptomatic bowel stricture and/or stenosis not passable in endoscopy (including pediatric endoscope).
6. Certain situations related to CD surgery (see protocol for details).
7. Certain situations related to CD treatments (see protocol for details).
8. History of colonic cancer or colonic low grade or high-grade dysplasia adenomatous polyps, and/or at the screening endoscopy, evidence of low grade or high grade dysplasia adenomatous polyps (fully removed or not).
9. Subject with history of, or diagnosed with, the following during screening: primary sclerosing cholangitis, autoimmune hepatitis, and primary biliary cirrhosis.
10. Serious illness requiring hospitalization (not related to CD) within 4 weeks prior to screening.
11. Subject with certain infectious conditions (please see protocol for details).
12. Subject with uncontrolled ischemic heart disease and/or a history of congestive heart failure with New York Heart Association (NYHA) class 3 or 4 symptoms.
13. Subject with a known family or personal history of congenital or acquired long QT syndrome, or subjects with a marked baseline prolongation of QT/ heart-rate-corrected QT (QTc) interval (eg, repeated demonstration of a QTc interval [Fridericia correction] > 450 milliseconds [msec] for male and > 460 msec for female).
14. Subject with a history of torsade de pointe (TdP).
15. Acute or chronic clinically relevant pulmonary, hepatic, or renal functional abnormality, encephalopathy, neuropathy or unstable central nervous system pathology such as seizure disorder, or any other clinically significant medical problems as determined by physical examination, laboratory screening tests, and/or medical history (note: treated autoimmune hypothyroidism and autoimmune diabetes are allowed).
16. Subjects who received live vaccine within 3 months prior to screening and/or subject who is planning to receive such a vaccine during the study duration.
17. Subject with the following hematological and biochemical laboratory parameters obtained during the screening period: a. Hemoglobin ≤ 8.0 g/dL. b. Absolute neutrophil count < 750/mm3 . c. Platelets < 100,000 /mm3 d. eGFR < 60 mL/min/1.73 m2 e. Total serum bilirubin > 1.5 x ULN (except if related to pre-existing and documented Gilbert syndrome) f. Aspartate aminotransferase and/or alanine aminotransferase > 2 x ULN.
18. Subject who does not meet the washout period requirements prior to the screening endoscopy as described in the prohibited medication section of the study protocol.
19. Use of any investigational or nonregistered product within 5 half lives preceding baseline and during the study.
20. Subjects previously treated with obefazimod.
21. subjects with a known hypersensitivity to the active substance or to any of the excipients.
22. Illicit drug or alcohol abuse or dependence.
23. Subject who is committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
24. Any condition, which in the opinion of the investigator, could compromise the subject’s safety or adherence to the study protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. For induction and maintenance phase: change from baseline in CDAI score at Week 12 and Week 52.

Secondary endpoints 15

1. For Induction and Maintenance phase: (efficacy) Change from baseline in SES-CD at Week 12 and at Week 52 respectively.
2. For Induction phase and Maintenance phase: (efficacy) Proportion of subjects with endoscopic response at Week 12 and at Week 52 respectively.
3. For Induction phase and Maintenance phase: (efficacy) Proportion of subjects with no SES-CD ulcer subscore > 1 in at least one segment at Week 12 and at Week 52 respectively.
4. For Induction phase and Maintenance phase: (efficacy) Proportion of subjects with CDAI clinical remission at Week 12 and at Week 52 respectively.
5. For Maintenance phase: (efficacy) Proportion of subjects with sustained CDAI clinical remission at Week 52.
6. For Induction phase and Maintenance phase: (efficacy) Proportion of subjects with PRO-2 clinical remission at Week 12 and at Week 52 respectively.
7. For Induction phase and Maintenance phase: (efficacy) Proportion of subjects with CDAI clinical response at Week 12 and at Week 52 respectively.
8. For Induction phase and Maintenance phase: (efficacy) Proportion of subjects with PRO-2 clinical response at Week 12 and at Week 52 respectively
9. For Induction phase and Maintenance phase: (efficacy) Proportion of subjects with CDAI clinical response and endoscopic response at Week 12 and at Week 52 respectively
10. For Induction phase and Maintenance phase: (efficacy) Proportion of subjects with endoscopic remission at Week 12 and at Week 52 respectively
11. For Induction phase, Maintenance and Extension phase: Safety Incidence of all treatment-emergent adverse events (TEAEs), causally related TEAEs, all serious adverse events (SAE) and causally related SAEs.
12. For Induction, Maintenance and Extension phase: Safety, Incidence of AEs leading to discontinuation
13. For Induction, Maintenance and Extension phase: (safety) incidence of adverse events of special interest (AESIs)
14. For Induction, Maintenance and Extension phase: (safety) Incidence and severity of laboratory abnormalities and change from baseline in laboratory values
15. For Induction and Maintenance phase: PK, Obefazimod and its metabolites plasma concentrations at baseline and at specified timepoints during Induction and Maintenance and PK parameters as determined by population PK analysis

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Abivax

Sponsor organisation

Abivax

Address

7 Boulevard Haussmann

City

Paris

Postcode

75009

Country

France

Scientific contact point

Organisation

Abivax

Contact name

Clinical Operations

Public contact point

Organisation

Abivax

Contact name

Clinical Operations

Third parties 12

Locations

11 EU/EEA countries · 113 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 238 files

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

Application history

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