ABTECT-2 – ABX464 Treatment Evaluation for ulcerative Colitis Therapy -2

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

8 Jun 2023 → 15 Jul 2025

Decision date (initial)

2023-05-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Abivax

External identifiers

EU CT number

2022-500536-11-01

ClinicalTrials.gov

NCT05507216

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

To compare the efficacy of obefazimod versus placebo on endoscopic improvement and symptomatic remission.

Secondary objectives 4

1. To compare the efficacy of obefazimod versus placebo on clinical remission.
2. To compare the efficacy of obefazimod versus placebo on clinical response.
3. To compare the efficacy of obefazimod versus placebo on histologic-endoscopic mucosal improvement (HEMI).
4. To evaluate the safety profile of obefazimod versus placebo during induction.

Conditions and MedDRA coding

Moderately to severely active ulcerative colitis

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 8

1. Male or female (at birth) at least 16 years old except in EU/EEA, Israel, Serbia and Ukraine, where subjects must be at least 18 years old at the time of eligibility assessment. Where enrolment of adolescent subjects is allowed, adolescent subjects must weigh ≥ 40 kg and meet the definition of Tanner Stage 5 at screening.
2. Subjects must understand, sign and date the written voluntary informed consent form at the visit prior to any protocol-specific procedures. For under-aged subjects, national requirements regarding consent should also be met.
3. Documented diagnosis of ulcerative colitis, confirmed by endoscopy and histology. Should endoscopy/histology results not be available at screening, results from endoscopy and biopsies taken at screening may be used.
4. Active disease defined by modified Mayo score (MMS) ≥ 5 with rectal bleeding subscore (RBS) ≥ 1 and endoscopy subscore (MES) of 2 or 3 (confirmed by central reader).
5. Subjects with documented inadequate response (defined as lack of response, loss of response and/or intolerance) to at least one of the following treatments: corticosteroids (CS), immunosuppressant (IS), biologic or biosimilar therapies, S1P receptor modulators, JAK inhibitors and/or new drugs approved during the study (note: inadequate response to only 5-ASA or sulfasalazine is not accepted).
6. Women of childbearing potential (WOCBP) subjects and male subjects with WOCBP partner must agree to comply with contraception requirements as described in Section 4.5. (Contraception) of the protocol.
7. Subjects able and willing to comply with study visits and procedures as per protocol.
8. Subjects should be affiliated to a health insurance policy whenever required by a participating country or state.

Exclusion criteria 27

1. Subjects with ulcerative colitis (UC) limited to an isolated proctitis ( <15cm from anal verge) determined by endoscopy central reading.
2. Subjects with primary sclerosing cholangitis or autoimmune hepatitis.
3. Subjects who had inadequate response to 5-aminosalicylic acid (5-ASA) or sulfasalazine therapy only.
4. Subjects with Crohn’s disease (CD), presence or history of fistula, indeterminate colitis, infectious/ischemic colitis or microscopic colitis (lymphocytic and collagenous colitis).
5. History or current evidence of toxic megacolon, fulminant colitis, bowel perforation.
6. History of colonic cancer or colonic low grade or high grade dysplasia adenomatous polyps, and/or at the screening endoscopy, evidence of colonic cancer or evidence of low grade or high grade dysplasia adenomatous polyps (fully removed or not).
7. Recent or planned bowel surgery or history of proctocolectomy or partial colectomy or current stoma.
8. Subjects on antidiarrheals including those working on motility (e.g, loperamide, diphenoxylate with atropine, etc.).
9. Subjects on probiotics (e.g., Culturelle® [Lactobacillus GG, i-Health, Inc.], Saccharomyces boulardii).
10. Subjects who do not meet the washout period requirements prior to the screening endoscopy as described in the prohibited medication section of the study protocol.
11. Subjects with hematological and biochemical laboratory parameters, obtained during the screening period, that meet specified values as described in the protocol.
12. Subjects with certain conditions (infection), as described in the protocol.
13. Subjects with an uncontrolled ischemic heart disease and/or a history of congestive heart failure with New York Heart Association (NYHA) class 3 or 4 symptoms.
14. Subjects with a family or personal history of congenital or acquired long QT syndrome, or subjects with a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval [Fridericia correction] >450 milliseconds for male and > 460 milliseconds for female).
15. Subjects with a history of torsade de pointe (TdP).
16. 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 and/or laboratory screening tests and/or medical history (note: treated autoimmune hypothyroidism and autoimmune diabetes are allowed).
17. Acute or chronic pancreatitis, determined by amylase and/or lipase elevations ≥ 3 ULN at screening and abnormal imaging results (CT, MRI or ultrasound) during the screening period.
18. History or active malignancy including non-melanoma skin cancer (subjects with a 5-year disease free survival are eligible).
19. Serious illness requiring hospitalization within 4 weeks prior to screening (except UC flare).
20. Subjects previously treated with obefazimod.
21. Subjects with a known hypersensitivity to the active substance or to any of the excipients.
22. 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.
23. Illicit drug or alcohol abuse or dependence.
24. Subjects who received live vaccine within 3 months prior to screening and/or who’s planning to receive such a vaccine during the study duration.
25. Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding baseline, whichever is longer, and during the study.
26. Subjects committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
27. 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. Co-primary endpoints: Proportion of subjects who achieve endoscopic improvement at week 8 and proportion of subjects with symptomatic remission at week 8.

Secondary endpoints 8

1. Proportion of subjects who achieve clinical remission at week 8.
2. Proportion of subjects with clinical response at week 8.
3. Proportion of subjects with HEMI per Geboes scoring at week 8.
4. Incidence of all treatment-emergent adverse events (TEAEs), causally related TEAEs, all serious TEAEs and causally-related serious TEAEs classified by severity.
5. Incidence of TEAEs leading to investigational medicinal product (IMP) discontinuation and study discontinuation.
6. Incidence of treatment-emergent adverse events of special interest (AESIs).
7. Incidence of clinically significant laboratory abnormalities.
8. Incidence of clinically significant abnormalities regarding vital signs and electrocardiograms (ECGs).

Investigational products

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

Test 2

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 11

Locations

14 EU/EEA countries · 102 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 477 files

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

Application history

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