ABTECT - Maintenance

JRCT ID: jRCT2031230257

Registered date:26/07/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Ulcerative colitis
• Date of first enrollment: 03/08/2023
• Target sample size: 80
• Countries of recruitment: Argentina,Japan,Australia,Japan,Austria,Japan,Belgium,Japan,Bulgaria,Japan,Brazil,Japan,Canada,Japan,China,Japan,Czech Republic,Japan,France,Japan,Germany,Japan,Greece,Japan,Hungary,Japan,India,Japan,Israel,Japan,Italy,Japan,Korea,Japan,Mexico,Japan,Netherlands,Japan,New Zealand,Japan,Poland,Japan,Portugal,Japan,Romania,Japan,Serbia,Japan,Slovakia,Japan,Slovenia,Japan,Spain,Japan,Switzerland,Japan,Turkey,Japan,UK USA,Japan
• Study type: Interventional

Intervention(s)

This is a multicenter, randomized, blinded study to evaluate the long-term efficacy and safety of ABX464 50mg and 25mg administered once daily (QD) as maintenance therapy following completion of 8-week induction treatment (Induction Studies ABX464-105 or ABX464-106) in subjects with moderately to severely active UC who have inadequate response, no response, a loss of response, or an intolerance to either conventional therapies [corticosteroids, immunosuppressant (i.e. azathioprine, 6-mercaptopurine*, methotrexate*)] and/or advanced therapies [biologics (TNF inhibitors, anti-integrins, anti-IL-23), and/or S1P receptor modulators*, and/or JAK inhibitors] (* not approved in Japan).
This study is the maintenance phase of the Phase 3 clinical development program sequential to previous induction studies ABX464-105 and ABX464 106.
All eligible subjects who have completed either one of the induction studies above mentioned, will be encouraged to take part in the present ABX464-107 maintenance study and will be randomized to either a double blind, placebo-controlled part (Part #1) or allocated to ABX464 50mg or 25mg blinded ABX464 treatment arms (Part #2) depending on their clinical response at the end of induction as shown below.
This study consists of a 44-week treatment phase and a 28-days follow-up period concluding in the End of Study (EoS) visit.

Subjects' eligibility will be confirmed at the end of the induction study (i.e., either ABX464-105 or ABX464-106). Entry criteria will mainly be based on subject's willingness to participate to the maintenance study and induction study completion. For all inclusion/exclusion criteria, see the dedicated section of the study protocol.
Subjects experiencing a clinical response (i.e., responders) at the end of the induction studies will be randomized into study Part #1, while non-responder subjects will be randomized/allocated into study Part #2.
Among both induction studies, approximatively 450 subjects (excluding placebo responder subjects) are expected to be assessed as responders and randomized as follows according to their induction treatment:
-ABX464 - Dose 50 mg QD: approximatively 150 subjects
-ABX464 - Dose 25 mg QD: approximatively 150 subjects (100 subjects from the 25mg induction dose group and 50 subjects from the 50mg induction group)
-Placebo: approximatively 150 subjects (50 subjects from the 25mg induction dose group and 100 subjects from the 50mg induction group)
Subjects with clinical response on active treatment in the induction studies will have the 2:1 odd, i.e., 2/3 chance of being randomized to active treatment during maintenance. Subjects with clinical response and who were dosed with placebo in the induction studies will continue to receive placebo during the maintenance treatment (blinded).
Randomization will be stratified according to the following:
-Clinical Remission status (yes/no)
-Induction dose (50mg or 25mg)
-Subject who are treated with oral corticosteroids at baseline of the maintenance (yes/no)
Subjects without a clinical response at the end of the induction studies (600 subjects expected) may opt in the maintenance study Part #2. They will be randomized/allocated into the two ABX464 blinded dose levels: ABX464 - Dose 50 mg QD or ABX464 - Dose 25 mg QD
Allocation/randomization will be performed according to the following:
-Non-responder subjects who had received 50mg during induction will be allocated into the 50mg blinded dose group
-Non-responder subjects who had received 25mg during induction will be allocated into the 25mg blinded dose group
-Non-responder subjects who had received placebo during induction will be randomized into the 25mg and 50mg blinded dose groups according to a 1:1 ratio
From Day 1 onwards, subjects will be seen at the investigational site at Week 4, (and at Week 8 for Part #2 subjects only), then every 8 weeks up to Week 44 and 4 weeks after the last dose for an end of study visit. An end of study visit will also be performed should the subjects not be eligible for the long-term extension safety study.
For subjects joining Part #2 after relapse in Part #1, if there is no scheduled visit within 4 weeks (+/- 2 weeks), a site visit should be performed 4 weeks later as an unscheduled visit (week 4, SoA, Table 5.1).
At week 44, a flexible sigmoidoscopy with biopsies from the most severely affected area will be performed. If lesions are healed, biopsies should be taken from approximately the same area of the baseline endoscopy (see section 5.3.6). Endoscopies will be centrally read. Sigmoidoscopy might be substituted by a full colonoscopy if requested by national medical practices and/or guidelines. Biopsies will be also centrally analyzed.
e-Diaries will be used to collect stool frequency, rectal bleedings, nocturnal bowel movements, bowel urgency, fatigue NRS as well as study drug intake times.
During ABTECT Maintenance Part #1 at any time should a study doctor suspect a subject is experiencing an UC relapse, the following sequence must be applied:
-The study doctor must check whether the subject meets the relapse definition (pMMS increase >= 2 points from Maintenance baseline with an increase of the rectal bleeding score >= 1 point).
-If the relapse definition is met: the subject will be invited to come back to the site approximately 2 weeks after to perform a "relapse confirmatory visit" (RCV).
-At the relapse confirmation visit, PI checks IRT to see if a second event of relapse is met before or at RCV. If it is not confirmed, the subject will remain in Maintenance Part #1.
-If it is confirmed and the study doctor considers the subject's state of health justifies it (suspicion of disease worsening), it is allowed to perform the endoscopy at the time of the RCV, but it is not a requirement.
-Connect to the IRT to confirm the relapse is not met and that the subject remains in Part #1.
Should a relapse be confirmed, the following will apply:
-The subjects will exit the Maintenance Part #1 and be allocated into Maintenance Part #2 to receive ABX464, 50mg QD. For this purpose, the investigator will connect to the IRT to proceed to subject's transfer from Part #1 to Part #2.
-The study doctor will ask the subject to mention whether the symptoms are improving or not by completing the eDiary assiduously.
-During the weeks that follow RCV, should the study doctor suspect a UC worsening, the subject will be invited to come back to perform an endoscopy. This endoscopy should be performed within approximately 6 to 8 weeks maximum after the RCV. The endoscopy must be recorded for central reading purpose, but the worsening definition will be first checked locally during the exam.If the disease worsening definition is confirmed during the endoscopy, the subject needs to terminate their participation to the study. Biopsies must be taken at this occasion so the subject won't have to redo an unnecessary endoscopy to fulfil the End of Treatment (EoT) visit requirements.If possible, according to site organization, the EoT visit can take place once the disease worsening is confirmed. If not the EoT will be scheduled at the earliest convenience. An End of Study visit will be performed 4 weeks after EoT. The endoscopy that confirmed the disease worsening will be duly sent to the central reader to be assessed as EoT endoscopy. If the disease worsening definition is not met, the subject will remain in Maintenance Part #2 and be treated with ABX464 50 mg QD.

Outcome(s)

• Primary Outcome: The study primary objective is to evaluate the efficacy of ABX464 versus placebo on the proportion of subjects in clinical remission at Week 44.

Key inclusion & exclusion criteria

• Age minimum: >= 16age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.Subjects must have completed the induction treatment study (ABX464-105 or ABX464 106), and subjects' clinical response status must be available.
2.Subjects with a valid endoscopy performed at the end of the induction study and results from central reader available at Day 1.
3.Subjects must understand, sign and date the written voluntary informed consent form at the visit prior to any protocol-specific procedures. For under-aged subjects, national requirements regarding consent should also be met.
4.Women of childbearing potential (WOCBP) subjects and male subjects with WOCBP partner must agree to use highly effective contraception methods as stated in Section 4.4. (Contraception) of this protocol.
5.Subjects must be able and willing to comply with study visits and procedures as per protocol.

Exclude criteria

1.Subjects who permanently discontinued the study treatment during the induction study (either ABX464-105 or ABX464-106).
2.Subjects who have developed any major illness/condition or evidence of an unstable clinical condition (except UC) during the induction study that, in the investigator's judgment, will substantially increase the risk to the participant if he or she participates in the study.
3.Subjects who plan to participate in other investigational studies during the maintenance study.
4.Pregnant or breast-feeding women or male subject of a pregnant partner,
5.Male or female subjects planning a pregnancy within the coming 12 months.
6.Subjects who have not adhered to abstinence of prohibited and/or concomitant medications.
7.Any changes in the laboratory values during the induction period that correspond with the following:
-Hemoglobin <= 8.0 g dL-1
-Absolute neutrophil count < 750 mm-3
-Platelets < 100,000 mm-3
-Creatinine clearance < 60 mL.min-1 (Cockcroft-Gault formula)
-Total serum bilirubin > 1.5 x ULN
-Alkaline phosphatase, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2 x ULN

Related Information

• Primary Sponsor: Shono Masushi
• Secondary ID(s): NCT05535946