|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Moderate to Severe Ulcerative Colitis
|Medical condition in easily understood language
|In Ulcerative Colitis the lining of the colon becomes inflamed and develops tiny open sores that produce pus and mucous. This causes abdominal discomfort and frequent emptying of the colon (diarrhoea)
|Diseases [C] - Digestive System Diseases [C06]
|E.1.2 Medical condition or disease under investigation
|Acute ulcerative colitis
|System Organ Class
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|The primary objective of the study is to evaluate the long-term safety of ABX464 given at 25 mg once daily in subjects with Moderate to Severe Active Ulcerative Colitis.
|Secondary objectives of the trial
|The secondary objectives are:
1. To evaluate the long-term effect of ABX464 on clinical remission;
2. To evaluate the long-term effect of ABX464 on endoscopic remission;
3. To evaluate the long-term effect of ABX464 on clinical response;
4. To evaluate the long-term effect of ABX464 on endoscopic improvement;
5. To evaluate the long-term effect of ABX464 on inflammatory markers (C-reactive protein (CRP), calprotectin);
6. To evaluate the safety profile of ABX464;
7. To evaluate the effect of ABX464 on miR-124 expression in total blood at every timepoint defined in the schedule of assessment.
8. To evaluate the effect of ABX464 on cardiac function as assessed through echocardiograms.
|Trial contains a sub-study
|Principal inclusion criteria
|1. Subjects who previously completed the ABX464-102 or ABX464-104 clinical studies;
2. Subjects should be in endoscopic improvement with a rectal bleeding sub-score = 0 point at the end of treatment period in the previous study (ABX464-102 or ABX464-104). Endoscopic improvement is defined as: a Mayo endoscopic sub score of ≤1 ;
3. Subjects able and willing to comply with study visits and procedures;
4. Subjects must understand, sign and date the written voluntary informed consent form at the visit prior to any protocol-specific procedures;
5. Women of childbearing potential and men receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for at least 21 days after end of study or early termination. Women must be 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. The WOCB must be willing to perform once a month a urine pregnancy test. Highly effective methods of contraception include true abstinence, intrauterine device (IUD) or hormonal contraception aiming at inhibition of ovulation, intrauterine hormone releasing system, bilateral tubal ligation, vasectomized partner. True abstinence is defined when this is in line with the preferred and usual lifestyle of the subject. This recommendation also applies to WOCBP with infrequent or irregular menstrual cycle. Female and male subjects must not be planning pregnancy during the trial and for at least 21 days post completion of their participation in the trial. In addition, male subjects should use condom during the trial and for at least 21 days post completion of their participation in the study. Male subjects must not donate sperm as long as contraception is required. For the purpose of this protocol, a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. Finally, a man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy;
6. Subjects should be affiliated to a social security regimen (for French sites only).
|Principal exclusion criteria
|1. Subjects who have developed any major illness/condition or evidence of an unstable clinical condition (except UC) that, in the investigator's judgment, will substantially increase the risk to the participant if he or she participates in the study;
2. Subjects with any other severe acute or chronic medical or psychiatric condition or laboratory or electrocardiogram (ECG) abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study;
3. Subjects who are participating or plan to participate in other investigational studies (other than induction study) during the study.
|E.5 End points
|Primary end point(s)
|Number of Adverse Events (AEs) in ABX464 treated subjects.
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|1. Percentage of subjects reaching clinical remission at yearly visits.
2. Percentage of subjects reaching endoscopic remission at yearly visits.
3. Percentage of subjects reaching clinical response at yearly visits.
4. Percentage of subjects reaching endoscopic improvement at yearly visits.
5. The change from Baseline in CRP and fecal calprotectin levels.
6a.Number and rate of all AEs and causally-related AEs, all Serious Adverse Events (SAEs) and causally-related SAEs, all AEs of Specific Interest (AESIs) and causally-related AESIs, classified by severity;
6b. Incidence of AEs leading to investigational medicinal product discontinuation;
6c. The number of clinically-significant laboratory abnormalities.
7. Change relative to baseline in miRNA-124 expression in total blood at every defined timepoint.
8a. Absolute (%) change from baseline echocardiogram of left ventricular ejection fraction (LVEF) as measured by 2-dimensional echocardiography;
8b. Number of subjects with a clinically relevant reduction (change from baseline echocardiogram) of LVEF, defined as > 10% reduction (absolute percentage points) to a value < 50%;
8c. Absolute (%) change in left ventricular global longitudinal strain (LVGLS) from baseline echocardiogram;
8d. Number of subjects with a relative percentage reduction in LVGLS by > 15% from the previous value;
8e. Number of subjects with a reduction of LVEF > 10% (absolute percentage points) to a value ≥ 50% with an accompanying fall in LVGLS > 15%;
8f. Number of subjects with reduction in LVEF by > 10% (absolute percentage points) to a value ≥ 50%;
8g. Changes from baseline echocardiography of other echocardiographic parameters as described in the Statistical Analysis Plan (SAP), including 2-dimensional volumes, right ventricle size and systolic function and valve function.
|Timepoint(s) of evaluation of this end point
|1.-4. Yearly visits
7. Yearly visits
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months