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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Abivax

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Decision date (initial)

2022-12-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Abivax

External identifiers

EU CT number

2022-500536-11-00

ClinicalTrials.gov

NCT05507216

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

To compare the efficacy of ABX464 versus placebo on clinical remission.

Secondary objectives 5

1. To compare the efficacy of ABX464 versus placebo on endoscopic improvement.
2. To compare the efficacy of ABX464 versus placebo on clinical response as per Modified Mayo Score (MMS).
3. To compare the efficacy of ABX464 versus placebo on symptomatic remission.
4. To compare the efficacy of ABX464 versus placebo on histologic-endoscopic mucosal improvement (HEMI).
5. To compare ABX464 safety profile versus placebo during induction.

Conditions and MedDRA coding

Moderately to severely active ulcerative colitis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Men or women at least 16 years old; Adolescent subjects will only be enrolled if approved by the country regulatory/health authority. If these approvals have not been granted, only subjects = 18 years old will be enrolled. To be eligible, adolescent subjects must weight = 40 kg and meet the definition of Tanner Stage 5 at the screening visit.
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 UC > 90 days prior to baseline, confirmed by endoscopy and histology. Should histology results not be available at screening, results from 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 or loss of response or intolerance) to at least one of the following treatments: corticosteroids, immunosuppressant, biologic therapies, S1P receptor modulators and/or JAK inhibitors and/or new drugs approved 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 use highly effective contraception methods as stated in Section 4.4. (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 26

1. Subjects with ulcerative colitis limited to an isolated proctitis (≤ 15cm from anal verge).
2. 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.
3. Subjects with hematological and biochemical laboratory parameters obtained during the screening period, as described in the protocol.
4. Subjects with certain conditions (infection), as described in the protocol.
5. 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.
6. 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 or Bazett correction] >450 milliseconds for male and > 460 milliseconds for female).
7. Subjects with a history of torsade de pointe (TdP).
8. Acute or chronic of clinically relevant pulmonary, hepatic, pancreatic 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 hypothyroidy and autoimmune diabetes are allowed).
9. History or active malignancy (subjects with a 5-year disease free survival are eligible).
10. Serious illness requiring hospitalization within 4 weeks prior to screening (except UC flare).
11. Subjects previously treated with ABX464.
12. Subjects with primary sclerosing cholangitis or autoimmune hepatitis.
13. Pregnant or breast-feeding women.
14. Illicit drug or alcohol abuse or dependence.
15. 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.
16. 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.
17. Any condition, which in the opinion of the investigator, could compromise the subject’s safety or adherence to the study protocol.
18. Subjects who have failed on 5-aminosalicylic acid (5-ASA) therapy only.
19. Subjects with Crohn’s disease (CD) or presence or history of fistula, indeterminate colitis, infectious/ischemic colitis or microscopic colitis (lymphocytic and collagenous colitis).
20. History or current evidence of toxic megacolon, fulminant colitis, bowel perforation.
21. History of colon cancer, past or current evidence of low grade or high grade of colonic dysplasia and/or adenomatous polyps that have not been completely removed.
22. Recent or planned bowel surgery or history of proctocolectomy or partial colectomy or current stoma.
23. Subjects on antidiarrheals (e.g., loperamide, diphenoxylate with atropine, etc.).
24. Subjects on probiotics (e.g., Culturelle® [Lactobacillus GG, i-Health, Inc.], Saccharomyces boulardii).
25. Subjects with a known hypersensitivity to the active substance or to any of the excipients.
26. Subjects committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of subjects who achieve clinical remission per Modified Mayo Score at week 8.

Secondary endpoints 9

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

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

5 Rue De La Baume

City

Paris

Postcode

75008

Country

France

Scientific contact point

Organisation

Abivax

Contact name

Clinical Operations

Public contact point

Organisation

Abivax

Contact name

Clinical Operations

Third parties 9

Locations

6 EU/EEA countries · 41 investigational sites

By country

Investigational sites

Application history

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