|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 assess in all patients the long-term efficacy of ABX464 given at 50 mg QD on clinical remission at week 48 compared to the induction study baseline (ISB).
|Secondary objectives of the trial
-the clinical remission at week 48 compared to the baseline of the open label study (BOLS)
- the proportion of patients with glucocorticoid-free clinical remission at W48
-the effect of ABX464 50 mg QD:
~on Modified Mayo Score at week 48 and W96; and on partial MMS, among patients, at every study visit compared to ISB (Induction study baseline)
~on endoscopic improvement and remission and sustained endoscopic improvement and remission, by segment at W48 compared to ISB and BOLS
~on stool and rectal bleeding frequency at every study visit compared to BOLS
~on fecal calprotectin and CRP levels at W24, 48, 60, 72, 84, 96 compared to BOLS
~on clinical response at W48 compared to ISB and BOLS
~on RNA later at W48 and 96 and in total blood at W24, 48 and 96
~on patients’ QoL at W24 and W48 compared to BOLS
~on the rectal/sigm. infiltrates at W48 compared to ISB and BOLS
~on cardiac function through echocardiogr.
-the LT safety profile of ABX464 50 mg QD
|Trial contains a sub-study
|Principal inclusion criteria
|A patient will be eligible to participate in this study if ALL the following criteria are met:
Patients must have completed the 16-week (± 4 days) induction treatment period (ABX464-103);
Patients are able and willing to comply with study visits and procedures as per protocol;
Patients should understand, sign and date the written voluntary informed consent form prior to any protocol-specific procedures are performed;
Patients should be affiliated to a social security regimen (for French sites only);
Females and males receiving the study treatment (potentially in combination with immunosuppressant) and their partners must agree to use a highly effective contraceptive method during the study and for 6 months (180 days) after end of study or early termination. Contraception should be in place at least 2 weeks prior to screening. Women must be surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy) or in the postmenopausal state (no menses for 12 months without an alternative medical cause)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) 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 patient. 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. Female and male patients must not be planning pregnancy during the trial and for 6 months post completion of their participation in the trial. In addition, male patients should use condom during the trial and for 6 months (180 days) post completion of their participation in the study. Male patients must not donate sperm as long as contraception is required.
Criteria that should be met by patients at week 48 to be eligible for 48
additional weeks of study treatment.
. Patients should be in clinical response. Clinical response is defined
as: a reduction in Modified Mayo Score = 2 points and = 30 % from
baseline (induction) with an accompanying decrease in rectal bleeding
sub-score = 1 point or absolute rectal bleeding sub-score = 1 point.
. Patients able and willing to continue the study treatment and who
are compliant with study visits and procedures and who signed the
update of the written voluntary informed consent.
|Principal exclusion criteria
|Patients who meet any of the following exclusion criteria will be excluded from the study:
Patients who had protocol deviation(s) in the induction study assessed as major by the investigator or the study sponsor
Patients who permanently discontinued study the treatment in induction study (ABX464-103) because of an adverse event (AE) regardless of relatedness to investigational product;
Patients 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;
Patients 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 patient inappropriate for
entry into this study;
Patients 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)
|Proportion of patients with clinical remission at week 48 compared to induction study baseline.
Clinical remission based on the Mayo Scoring system, is defined as: stool
frequency sub-score = 0 or 1 and rectal Bleeding sub-score = 0 and
endoscopy sub-score = 0 or 1 (modified to exclude friability).
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|The week 24 and 48 secondary endpoints are:
Reduction relative to baseline in Modified Mayo Score at week 48 and in partial Modified Mayo Score at every study visit among all patients.
Proportion of patients with either endoscopic improvement or/and endoscopic remission by segment at week 48 among all patients. Endoscopic improvement is defined as a Mayo endoscopic sub score of ≤1 (excluding friability). Endoscopic remission is defined as a Mayo endoscopic sub score of 0.
Proportion of patients with sustained endoscopic improvement or/and sustained endoscopic remission at week 48.
Sustained endoscopic improvement is defined as the number of patients with endoscopic improvement at week 48 among patients who had endoscopic improvement during the Induction study (at week 8 or week 16).
Sustained endoscopic remission is defined as the number of patients
with endoscopic remission at week 48 among patients who had
endoscopic remission during the Induction study (at week 8 or week
Proportion of patients with glucocorticoid-free clinical remission at week 48. Glucocorticoid-free clinical remission is defined as clinical remission in addition to not requiring any treatment with glucocorticoids for at least 8 weeks prior to week 48.
Reduction relative to baseline in stool and rectal bleeding frequency at every study visit.
Reduction relative to baseline in fecal calprotectin and CRP levels at week 24 and 48.
Proportion of patients with clinical response at week 48.
Clinical response is defined as: a reduction in Modified Mayo Score ≥ 2 points and ≥ 30 % from baseline with an accompanying decrease in rectal bleeding sub-score ≥ 1 point or absolute rectal bleeding sub-score ≤ 1 point.
Change relative to baseline in miRNA-124 expression in rectal/sigmoidal biopsies at week 48 and in total blood at week 24 and week 48.
Scores and changes from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) domains at week 24 and 48.
Reduction relative to ISB of infiltrate/histopathology (rectal/ sigmoidal biopsies) using the Robarts Histopathology Index (RHI), the Geboes and Nancy Histology Scoring Scales at week 48.
The week 96 secondary endpoints are:
. Reduction relative to baseline in Modified Mayo Score at week 96 and
in partial Modified Mayo Score at every study visit (week 48 to 96)
among all patients.
. Proportion of patients with either endoscopic improvement or/and
endoscopic remission by segment at week 96
. Proportion of patients with sustained endoscopic improvement
or/and sustained endoscopic remission at week 96.
. Reduction relative to baseline in stool and rectal bleeding frequency
at every study visit (week 48 to 96).
. Reduction relative to baseline in fecal calprotectin and CRP levels at
week 60, 72, 84 and 96.
. Proportion of patients with clinical response at week 96.
-Change relative to baseline in miRNA-124 expression in rectal/sigmoidal biopsies and in total blood at week 96.
The echocardiography secondary endpoints are:
-Absolute (%) change-from-previous echocardiogram of Left ventricle
Ejection Fraction (LVEF) as measured by 2- or 3-dimensional
-Number of subjects with a clinically relevant reduction (change-from
echocardiogram) of LVEF, defined as by > 10% reduction
(absolute percentage points) to a value < 50%.
-Absolute (%) change from-previous echocardiogram in Global
Longitudinal Strain (GLS).
-Number of subjects with a relative percentage reduction in GLS by >
15% from the previous echocardiogram.
-Number of subjects with a reduction of LVEF > 10% (absolute
percentage points) to a value = 50% with an accompanying fall in GLS >
-Number of subjects with reduction in LVEF by > 10% (absolute
percentage points) to a value = 50%.
-Changes from previous echocardiography of other echocardiographic
parameters as described in a standard protocol, including 2- and 3-
dimensional volumes, RV size and systolic function and valve function.
Safety endpoints are:
Number and rate of all adverse events, causally-related adverse events, all SAE and causallyrelated SAEs classified by severity.
Incidence of treatment-emergent serious adverse event, hospitalizations, total inpatient days.
Incidence of adverse events leading to investigational product discontinuation.
Number of clinically significant laboratory abnormalities.
|Timepoint(s) of evaluation of this end point
|1) MMS at week 48 and pMMS at every visit
2) at week 48
3) at week 48
4) at week 48
5) at every study visit
6) at week 24 and 48
7) at week 48
8) at week 24 and 48
9) at week 24 and 48
10) at week 48
11) at week 96
12) at week 96
13) at week 96
14) at every study visit
15) at week 60, 72, 84 and 96
16) at week 96
17) through the study
18) through the study
19) through the study
20) through the study
|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)
|Number of treatment arms in the trial
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