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Efficacy and Safety Study of ABX464 as Maintenance Therapy in Patients With Moderate to Severe Ulcerative Colitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04023396
Recruitment Status : Recruiting
First Posted : July 17, 2019
Last Update Posted : January 9, 2020
Sponsor:
Information provided by (Responsible Party):
Abivax S.A.

Brief Summary:
A phase 2b study to evaluate the long-term efficacy and safety study of ABX464 50mg as maintenance therapy in patients with moderate to severe Ulcerative Colitis.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: ABX464 Phase 2

Detailed Description:
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 ABX464-103 clinical study (induction study) and who are willing to continue their treatment. All subjects will receive ABX464 given at 50mg o.d regardless of their previous treatment and dose received in the ABX464-103 study (i.e. ABX464 100mg, ABX464 50mg, ABX464 25mg or Placebo). The enrolment in this follow-up study will be based on the willingness of the subject to carry on his/her participation. Subjects will be treated with ABX464 for an overall period of 48 weeks. Subjects will be followed up on a monthly basis.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 210 participants
Intervention Model: Single Group Assignment
Intervention Model Description: open-label, follow-up study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2b, Open-label, Efficacy and Safety Study of ABX464 as Maintenance Therapy in Patients With Moderate to Severe Ulcerative Colitis
Actual Study Start Date : October 1, 2019
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ABX464 50mg
All subjects will receive ABX464 administered at 50 mg o.d for an overall period of 48 weeks.
Drug: ABX464

ABX464

All subjects will receive ABX464 administered at 50 mg o.d for an overall period of 48 weeks.





Primary Outcome Measures :
  1. Proportion of patients with clinical remission at week 48 compared to baseline of induction study (ABX464-103) [ Time Frame: week 48 ]
    Clinical remission (based on the Mayo scoring system) is defined as: a rectal bleeding sub-score = 0, and an endoscopy sub-score ≤1 (excluding friability), and at least 1-point decrease in stool frequency sub-score from baseline to achieve a stool frequency sub-score ≤1


Secondary Outcome Measures :
  1. Change in Modified Mayo Score and in partial Modified Mayo Score [ Time Frame: From baseline to week 52 ]

    Change in Modified Mayo Score at week 48 and in partial Modified Mayo Score at every study visit among all patients.

    Modified Mayo Score evaluates ulcerative colitis stage, based on four parameters: stool frequency, rectal bleeding, endoscopic evaluation and Physician's global assessment. Each parameter of the score ranges from zero (normal or inactive disease) to 3 (severe activity).

    Partial Mayo score uses the 3 non-invasive components of the full Mayo Score (stool frequency, rectal bleeding and Physician's global assessment) and excludes the score for the endoscopic findings. Therefore the maximum score is reduced from 12 to 9 points.


  2. Endoscopic changes at week 48 [ Time Frame: week 48 ]

    Proportion of patients with endoscopic changes 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.


  3. Sustained endoscopic changes at week 48 [ Time Frame: week 48 ]
    Proportion of patients with sustained endoscopic changes at week 48. Sustained endoscopic changes is defined as the number of patients with endoscopic changes at week 48 among patients who had endoscopic changes during the Induction study (at week 8 or week 16 of study ABX464-103).

  4. Glucocorticoid-free clinical remission [ Time Frame: From baseline to week 48 ]
    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.

  5. Rectal bleeding [ Time Frame: from baseline to week 52 ]
    Change to baseline in stool and rectal bleeding frequency at every study visit.

  6. Fecal calprotectin and C-Reactive Proteine [ Time Frame: baseline, week 24, week 48 ]
    Change to baseline in fecal calprotectin and C-Reactive Proteine levels at week 24 and 48.

  7. Clinical response at week 48 [ Time Frame: baseline, week 48 ]
    Proportion of patients with clinical response at week 48. Clinical response is defined as: a reduction in Mayo Score ≥ 3 points and ≥ 30 % from baseline with an accompanying decrease in rectal bleeding sub-score ≥ 1 point or absolute rectal bleeding sub-score ≤ 1 point.

  8. miRNA-124 expression [ Time Frame: baseline, week 24 and week 48 ]
    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.

  9. Inflammatory Bowel Disease Questionnaire [ Time Frame: baseline, week 24, week 48 ]

    This questionnaire is a validated and reliable tool to measure health-related quality of life in adult patients with inflammatory bowel disease, ulcerative colitis, or Crohn's disease. It contains 32 questions, which are divided into four health domains: bowel symptoms (10 questions), systemic symptoms (5 questions), emotional function (12 questions), and social function (5 questions). For each question there are graded responses on a 7-point Likert scale, ranging from 1 (representing the "worst" aspect) to 7 (representing the "best" aspect). Thus, the total IBDQ score ranges from 32 to 224, with higher scores reflecting better well-being.

    For study purpose, scores and changes in the Inflammatory Bowel Disease Questionnaire domains will be collected and compared from baseline to week 24 and 48.


  10. Histopathological evaluation of the effect of ABX464 50 mg on the rectal/sigmoidal infiltrate based on Gebeos score [ Time Frame: week 48 ]

    Week 48 biopsies will be compared to biopsies taken during the induction study (ABX464-103) to assess the disease evolution at a tissue level, based on the Geboes Score.

    The scoring system is composed of 6 major grades that assess the structural changes (0), chronic inflammation (1), lamina propria neutrophils (2), neutrophils in the epithelium (3), crypt destruction (4) and erosion and ulcers (5).


  11. Histopathological evaluation of the effect of ABX464 50 mg on the rectal/sigmoidal infiltrate based on Nancy index scoring system [ Time Frame: week 48 ]

    Week 48 biopsies will be compared to biopsies taken during the induction study (ABX464-103) to assess the disease evolution at a tissue level, based on Nancy index scoring system.

    It is a 5-level classification from 0 (absence of significant histological disease) to 4 (severely active disease). Classification in each category depends on the presence or absence of ulceration, acute inflammatory cells infiltrate and chronic inflammatory cells infiltrate.


  12. Histopathological evaluation of the effect of ABX464 50 mg on the rectal/sigmoidal infiltrate based on the Robarts Histological index [ Time Frame: week 48 ]

    Week 48 biopsies will be compared to biopsies taken during the induction study (ABX464-103) to assess the disease evolution at a tissue level, based on the Robarts Histological Index.

    The score ranges from 0 (no disease activity) to 33 (severe disease activity) is based on evaluation of 4 parameters: chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in the epithelium and erosion and ulceration.


  13. Incidence and description of Adverse Events [ Time Frame: From baseline to week 52 ]

    Number and rate of all adverse events, causally-related adverse events, all serious adverse events and causally-related serious adverse events classified by severity.

    Incidence of treatment-emergent serious adverse events, hospitalizations, total inpatient days.

    Incidence of adverse events leading to investigational product discontinuation. Number of clinically significant laboratory abnormalities.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have completed the 16-week 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.

Exclusion Criteria:

  • Patients who had major protocol deviation(s) in the induction study;
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04023396


Contacts
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Contact: Paul GINESTE, PhD +33 1 53 83 09 61 paul.gineste@abivax.com
Contact: Jean-Marc STEENS, MD +33 1 53 83 09 61 Jean-marc.steens@abivax.com

Locations
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Sponsors and Collaborators
Abivax S.A.
Investigators
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Principal Investigator: Severine VERMEIRE, MD Universitaire Ziekenhuizen Leuven

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Responsible Party: Abivax S.A.
ClinicalTrials.gov Identifier: NCT04023396    
Other Study ID Numbers: ABX464-104
First Posted: July 17, 2019    Key Record Dates
Last Update Posted: January 9, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Abivax S.A.:
moderate to severe ulcerative colitis
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases