Study Evaluating the Long-term Safety and Efficacy of ABX464 in Active Ulcerative Colitis

Phase 2

Completed

Conditions: Ulcerative Colitis

Interventions: Drug: ABX464

Registration Number: NCT03368118

Lead Sponsor: Abivax S.A.

Brief Summary: This study is an open-label study aiming at evaluating the long-term safety and the efficacy profile of ABX464 given once a day (o.d) at 50 mg in subjects who have been previously enrolled in the ABX464-101 clinical study (induction study) and who are willing to continue their treatment.

Detailed Description: This study is an open-label study aiming at evaluating the long-term safety and the efficacy profile of ABX464 given once a day (o.d) at 50 mg in subjects who have been previously enrolled in the ABX464-101 clinical study (induction study) and who are willing to continue their treatment.

All subjects will receive ABX464 given at 50 mg o.d irrespective of their previous treatment received in the ABX464-101 study (i.e. ABX464 or Placebo).

The actual treatment received by a subject throughout the previous study (ABX464-101) will not be known at the time the subjects enter this follow-up study. This treatment group will be communicated (throughout the investigators) to the subjects at the end of the ABX464-101 study (planned in Q3/2018).

The enrolment in this follow-up study will be based on the willingness of the subject to carry on his/her participation and also based on investigator's judgement.

Subjects will be treated with ABX464 for an overall period of 48 months. Subjects will be followed up weekly during the first month, every two weeks during the second month and then on a monthly basis until M24, then quaterly from M24 to M48.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 22

Inclusion Criteria

A subject will be eligible for inclusion in this study only if ALL of the following criteria apply:

Subjects previously enrolled in the ABX464-101 clinical study who have completed the initial 2-month treatment phase;
Subjects able and willing to comply with study visits and procedures;
Subjects with hematological and biochemical laboratory parameters as follows at the D56 visit of the ABX464-101 study:
- Hemoglobin > 9.0 g dL-1;
- Absolute neutrophil count ≥ 750 mm-3;
- Platelets ≥ 100,000 mm-3;
- Total serum creatinine ≤ 1.3 x ULN (upper limit of normal);
- Creatinine clearance > 50 mL min-1 by the Cockcroft-Gault equation;
- Total serum bilirubin < 1.5 x ULN;
- Alkaline phosphatase, AST (SGOT) and ALT (SGPT) < 1.5 x ULN;
Subjects should understand, sign and date the written voluntary informed consent form at the enrolment visit prior to any protocol-specific procedures being performed;
Subjects should be affiliated to a social security regimen (for French sites only);
Females and males receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 3 months after end of study or early termination. Contraception should be in place at least 3 months prior to study participation. Women must be either postmenopausal (at least 12 months of amenorrhea), surgically sterile or if of childbearing potential must use a highly effective contraceptive method. Women of childbearing potential (WOCBP) will enter the study after confirmed menstrual period and a negative pregnancy test. Highly effective methods of contraception include: true abstinence, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), hormonal contraception (estrogen and progestogen or progestogen only) associated with inhibition of ovulation, bilateral tubal occlusion, vasectomized partner. True abstinence is defined when this is in line with the preferred and usual lifestyle of the subject. In each case of delayed menstrual period (over one month between menstruations) confirmation of absence of pregnancy is required. This recommendation also applies to WOCBP with infrequent or irregular menstrual cycle.

Exclusion Criteria

The following criterion should be checked at the time of screening. If this exclusion criterion applies, the subject will not be included in the study:

▪ Any condition, which in the opinion of the investigator, could compromise the subject's safety or the adherence to the study protocol.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ABX464 Treatment arm	ABX464	All subjects will receive ABX464 at 50 mg o.d for an overall period of 48 months.

Primary Outcome Measures

Name	Time	Method
Number of Treatment-emergent Adverse Events	Through subject study treatment, up to 48 months	Number of treatment-emergent adverse events in ABX464 treated subjects

Secondary Outcome Measures

Name	Time	Method
Partial Mayo Score	Up to Month 48	The change from Day 0 up to Month 48 in Partial Mayo Score; Partial Mayo score is an index and consists of 3 items: stool frequency, rectal bleeding and a physician global assessment of disease activity. Each parameter of the score ranges from zero (normal or inactive disease) to 3 (severe activity). The partial mayo score scale ranging is from 0 to 9. A higher (in negative) change from baseline shows a better clinical response
Number of Subjects With Clinical Response at Month 48	up to 48 months	Clinical response was defined as: reduction in Total Mayo Score (TMS) of at least 2 points and \>= 30 percent from baseline with an accompanying decrease in rectal bleeding sub-score of \>= 1 point or absolute rectal bleeding sub-score of \<= 1 point.
Number of Subjects With Clinical Remission at Month 48	up to 48 months	Clinical remission was achieved when all the following criteria were met in the components of the Mayo clinical Score: rectal bleeding sub-score = 0 central endoscopy sub-score \<= 1 stool frequency sub-score \<= 1
CRP Levels	Up to Month 48	The change from Day 0 up to Month 48 in CRP levels
Number of Subject With Endoscopic Improvement at Month 48	up to 48 Months	oEndoscopic improvement was achieved if the Mayo central endoscopic sub-score is 0 or 1.
Number of Subjects With Endoscopic Remission at Month 48	up to 48 months	Endoscopic remission was defined as Mayo central endoscopic sub-score = 0
Fecal Calprotectin	Up to Month 48	The change from Day 0 up to Month 48 in fecal calprotectin A higher (in negative) change shows a better efficacy
Number of Treatment-emergent Serious Adverse Events	Through subject study treatment, up to 48 months	The number of incidences of treatment-emergent serious adverse events
Number of Treatment-emergent Adverse Events of Special Interest	Through subject study treatment, up to 48 months	The number of incidences of treatment-emergent adverse events of special interest
Number of Adverse Events Leading to Investigational Product Discontinuation	Through subject study treatment, up to 48 months	The number of incidences of adverse events leading to investigational product discontinuation
Number of Specific Laboratory Abnormalities	Through first year of subject study treatment, 12 months	The number of incidences of specific laboratory abnormalities
SF-36 Quality of Life Questionnaire (SF-36 Physical Component)	Up to 24 months	Change from Day 0 up to 24 months in SF-36 Questionnaire scores; The SF-36 questionnaire is a self-administered questionnaire containing 36 items. It measures health on eight multi-item dimensions, covering functional status, well-being, and overall evaluation of health. These items are grouped in 2 distincts components: a physical component (SF-36 physical) and a mental component (SF-36 mental). This outcome describes the SF-36 physical component. Each item score ranging is from 0 to 100. A higher positive value in change indicate a better health status. The higher the change from baseline, the better improvement
SF-36 Quality of Life Questionnaire (SF-36 Mental Component)	Up to 24 months	Change from Day 0 up to 24 months in SF-36 Questionnaire scores; The SF-36 questionnaire is a self-administered questionnaire containing 36 items. It measures health on eight multi-item dimensions, covering functional status, well-being, and overall evaluation of health. These items are grouped in 2 distincts components: a physical component (SF-36 physical) and a mental component (SF-36 mental). This outcome describes the SF-36 mental component. Each item score ranging is from 0 to 100. A higher positive value in change indicate a better health status. The higher the change from baseline, the better improvement
Erythrocyte Sedimentation Rate (ESR) Levels	up to 48 Months	The change from Day 0 up to Month 48 in ESR levels
Total Mayo Score	Up to Month 48	The change from Day 0 up to Month 48 in Total Mayo Score. total mayo score is an index and consists of 4 items: stool frequency, rectal bleeding, flexible sigmoidoscopic examination, and a physician global assessment of disease activity. Each parameter of the score ranges from zero (normal or inactive disease) to 3 (severe activity). The total mayo score scale ranging is from 0 to 12 The change from baseline of this score is part of the clinical response definition: to get a clinical response, a reduction in Total Mayo score of at least 2 points is required. A higher (in negative) change shows a better clinical response.