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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Follow-up Phase IIa Study to Evaluate the Long-term Safety and Efficacy Profile of ABX464 Given at 50 mg Once Daily in Subjects With Moderate to Severe Active Ulcerative Colitis.

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: ABX464


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: open-label, follow-up study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABX464 Treatment arm<br>All subjects will receive ABX464 at 50 mg o.d for an overall period of 48 months. | Drug: ABX464<br>* All subjects will receive ABX464 given at 50 mg o.d for an overall period of 48 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of incidences of treatment-emergent adverse events | Number of incidences of treatment-emergent adverse events in ABX464 treated subjects. | Through study completion, 48 months + 1 additional month after study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Mayo Score | The change from Day 0 up to Month 48 in Total Mayo Score | Up to Month 48 | 
| Partial Mayo Score | The change from Day 0 up to Month 48 in Partial Mayo Score | Up to Month 48 | 
| UC worsening | The time of UC worsening | Up to Month 48 | 
| Fecal calprotectin | The change from Day 0 up to Month 48 in fecal calprotectin, CRP levels and ESR | Up to Month 48 | 
| CRP levels and ESR | The change from Day 0 up to Month 48 in CRP levels and ESR | Up to Month 48 | 
| Incidence of treatment-emergent serious adverse events | The number of incidences of treatment-emergent serious adverse events | Through study completion, 48 months | 
| Incidence of treatment-emergent adverse events of special interest | The number of incidences of treatment-emergent adverse events of special interest | Through study completion, 48 months | 
| Incidence of adverse events leading to investigational product discontinuation | The number of incidences of adverse events leading to investigational product discontinuation | Through study completion, 48 months | 
| Incidence of specific laboratory abnormalities | The number of incidences of specific laboratory abnormalities | Through study completion, 12 months | 
| SF-36 Quality of Life questionnaire | The scores and changes from Day 0 in SF-36 Questionnaire scores | Through study completion, 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABX464, Ulcerative Colitis