E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe Ulcerative Colitis. |
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E.1.1.1 | 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). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066678 |
E.1.2 | Term | Acute ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to evaluate the long-term safety of ABX464 given at 50 mg once daily in subjects with Moderate to Severe Active Ulcerative Colitis. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: ▪ To evaluate the long-term effect of ABX464 on clinical and endoscopic remission in subjects with Moderate to Severe Active Ulcerative Colitis assessed by the MCS. ▪ To evaluate the long-term effect of ABX464 on inflammatory markers (CRP, Calprotectin and ESR) ▪ To evaluate the long-term of ABX464 on Quality of Life (QoL) measured by the SF-36 questionnaire in subjects with Moderate to Severe Active Ulcerative Colitis until M24.
The echocardiography objective is: To evaluate the effect of ABX464 on cardiac function as assessed through echocardiograms. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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: o Hemoglobin > 9.0 g dL-1; o Absolute neutrophil count ≥ 750 mm-3; o Platelets ≥ 100,000 mm-3; o Total serum creatinine ≤ 1.3 x ULN (upper limit of normal); o Creatinine clearance > 50 mL min-1 by the Cockcroft-Gault equation; o Total serum bilirubin < 1.5 x ULN; o 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; ▪ Females and males receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 6 months after end of study or early termination. Contraception should be in place at least 3 months prior to study participation. 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. 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 an 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 participants should use condoms and should not donate sperm as long as contraception is required. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of incidences of treatment-emergent adverse events in ABX464 treated subjects. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoint of evaluation of this end point from day 0 to EoS. |
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E.5.2 | Secondary end point(s) |
The change from Day 0 in Total Mayo Score. ▪ The change from Day 0 in Partial Mayo Score. ▪ The time to UC worsening. ▪ The change from Day 0 in fecal calprotectin, CRP levels and ESR. ▪ The scores and changes from Day 0 in SF-36 Questionnaire scores ▪ The miR-124 expression at month 12, month 36 and month 48. ▪ The number of incidences of treatment-emergent serious adverse events. ▪ The number of incidences of treatment-emergent adverse events of special interest. ▪The number of incidences of adverse events leading to investigational product discontinuation. ▪ The number of incidences of specific laboratory abnormalities.
The echocardiography secondary endpoints are: ▪ Absolute (%) change-from-previous echocardiogram of Left ventricle Ejection Fraction (LVEF) as measured by 2- or 3 dimensional echocardiography ▪ Number of subjects with a clinically relevant reduction (change-from-previous echocardiogram) of LVEF, defined as by > 10% reduction (absolute percentage points) to a value < 50% ▪ Absolute (%) change in Global Longitudinal Strain (GLS) from-previous echocardiogram ▪ Number of subjects with a relative percentage reduction in GLS by > 15% from the previous value ▪ Number of subjects with a reduction of LVEF > 10% (absolute percentage points) to a value ≥ 50% with an accompanying fall in GLS > 15% ▪ 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time point of evaluation for secondary endpoints are throughout the study. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |