Ulcerative Colitis
Conditions
Keywords
ABX464, Ulcerative Colitis
Brief summary
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 ABX464-101 clinical study (induction study) and who are willing to continue their treatment.
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 ABX464-101 clinical study (induction study) and who are willing to continue their treatment. All subjects will receive ABX464 given at 50 mg o.d irrespective of their previous treatment received in the ABX464-101 study (i.e. ABX464 or Placebo). The actual treatment received by a subject throughout the previous study (ABX464-101) will not be known at the time the subjects enter this follow-up study. This treatment group will be communicated (throughout the investigators) to the subjects at the end of the ABX464-101 study (planned in Q3/2018). The enrolment in this follow-up study will be based on the willingness of the subject to carry on his/her participation and also based on investigator's judgement. Subjects will be treated with ABX464 for an overall period of 48 months. Subjects will be followed up weekly during the first month, every two weeks during the second month and then on a monthly basis until M24, then quaterly from M24 to M48.
Interventions
DRUGABX464
All subjects will receive ABX464 given at 50 mg o.d for an overall period of 48 months.
Sponsors
Orion Corporation, Orion Pharma
Abivax S.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
open-label, follow-up study
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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: * Hemoglobin \> 9.0 g dL-1; * Absolute neutrophil count ≥ 750 mm-3; * Platelets ≥ 100,000 mm-3; * Total serum creatinine ≤ 1.3 x ULN (upper limit of normal); * Creatinine clearance \> 50 mL min-1 by the Cockcroft-Gault equation; * Total serum bilirubin \< 1.5 x ULN; * 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; * Subjects should be affiliated to a social security regimen (for French sites only); * Females and males receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 3 months after end of study or early termination. Contraception should be in place at least 3 months prior to study participation. Women must be either postmenopausal (at least 12 months of amenorrhea), 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), intrauterine hormone-releasing system (IUS), hormonal contraception (estrogen and progestogen or progestogen only) associated with inhibition of ovulation, bilateral tubal occlusion, vasectomized partner. True abstinence is defined when this is in line with the preferred and usual lifestyle of the subject. 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.
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment-emergent Adverse Events | Through subject study treatment, up to 48 months | Number of treatment-emergent adverse events in ABX464 treated subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Partial Mayo Score | Up to Month 48 | The change from Day 0 up to Month 48 in Partial Mayo Score; Partial Mayo score is an index and consists of 3 items: stool frequency, rectal bleeding and a physician global assessment of disease activity. Each parameter of the score ranges from zero (normal or inactive disease) to 3 (severe activity). The partial mayo score scale ranging is from 0 to 9. A higher (in negative) change from baseline shows a better clinical response |
| Number of Subjects With Clinical Response at Month 48 | up to 48 months | Clinical response was defined as: reduction in Total Mayo Score (TMS) of at least 2 points and \>= 30 percent from baseline with an accompanying decrease in rectal bleeding sub-score of \>= 1 point or absolute rectal bleeding sub-score of \<= 1 point. |
| Number of Subjects With Clinical Remission at Month 48 | up to 48 months | Clinical remission was achieved when all the following criteria were met in the components of the Mayo clinical Score: rectal bleeding sub-score = 0 central endoscopy sub-score \<= 1 stool frequency sub-score \<= 1 |
| Number of Subject With Endoscopic Improvement at Month 48 | up to 48 Months | oEndoscopic improvement was achieved if the Mayo central endoscopic sub-score is 0 or 1. |
| Number of Subjects With Endoscopic Remission at Month 48 | up to 48 months | Endoscopic remission was defined as Mayo central endoscopic sub-score = 0 |
| Fecal Calprotectin | Up to Month 48 | The change from Day 0 up to Month 48 in fecal calprotectin A higher (in negative) change shows a better efficacy |
| CRP Levels | Up to Month 48 | The change from Day 0 up to Month 48 in CRP levels |
| Total Mayo Score | Up to Month 48 | The change from Day 0 up to Month 48 in Total Mayo Score. total mayo score is an index and consists of 4 items: stool frequency, rectal bleeding, flexible sigmoidoscopic examination, and a physician global assessment of disease activity. Each parameter of the score ranges from zero (normal or inactive disease) to 3 (severe activity). The total mayo score scale ranging is from 0 to 12 The change from baseline of this score is part of the clinical response definition: to get a clinical response, a reduction in Total Mayo score of at least 2 points is required. A higher (in negative) change shows a better clinical response. |
| Number of Treatment-emergent Adverse Events of Special Interest | Through subject study treatment, up to 48 months | The number of incidences of treatment-emergent adverse events of special interest |
| Number of Adverse Events Leading to Investigational Product Discontinuation | Through subject study treatment, up to 48 months | The number of incidences of adverse events leading to investigational product discontinuation |
| Number of Specific Laboratory Abnormalities | Through first year of subject study treatment, 12 months | The number of incidences of specific laboratory abnormalities |
| SF-36 Quality of Life Questionnaire (SF-36 Physical Component) | Up to 24 months | Change from Day 0 up to 24 months in SF-36 Questionnaire scores; The SF-36 questionnaire is a self-administered questionnaire containing 36 items. It measures health on eight multi-item dimensions, covering functional status, well-being, and overall evaluation of health. These items are grouped in 2 distincts components: a physical component (SF-36 physical) and a mental component (SF-36 mental). This outcome describes the SF-36 physical component. Each item score ranging is from 0 to 100. A higher positive value in change indicate a better health status. The higher the change from baseline, the better improvement |
| SF-36 Quality of Life Questionnaire (SF-36 Mental Component) | Up to 24 months | Change from Day 0 up to 24 months in SF-36 Questionnaire scores; The SF-36 questionnaire is a self-administered questionnaire containing 36 items. It measures health on eight multi-item dimensions, covering functional status, well-being, and overall evaluation of health. These items are grouped in 2 distincts components: a physical component (SF-36 physical) and a mental component (SF-36 mental). This outcome describes the SF-36 mental component. Each item score ranging is from 0 to 100. A higher positive value in change indicate a better health status. The higher the change from baseline, the better improvement |
| Erythrocyte Sedimentation Rate (ESR) Levels | up to 48 Months | The change from Day 0 up to Month 48 in ESR levels |
| Number of Treatment-emergent Serious Adverse Events | Through subject study treatment, up to 48 months | The number of incidences of treatment-emergent serious adverse events |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABX464 Treatment Arm All subjects will receive ABX464 at 50 mg o.d for an overall period of 48 months.
ABX464: All subjects will receive ABX464 given at 50 mg o.d for an overall period of 48 months. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | ABX464 Treatment Arm |
|---|---|
| Age, Continuous | 42.4 years STANDARD_DEVIATION 14.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Region of Enrollment Belgium | 3 participants |
| Region of Enrollment Hungary | 9 participants |
| Region of Enrollment Poland | 10 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 22 |
| other Total, other adverse events | 20 / 22 |
| serious Total, serious adverse events | 3 / 22 |
Outcome results
Primary
Number of Treatment-emergent Adverse Events
Number of treatment-emergent adverse events in ABX464 treated subjects
Time frame: Through subject study treatment, up to 48 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABX464 Treatment Arm | Number of Treatment-emergent Adverse Events | 145 events |
Secondary
CRP Levels
The change from Day 0 up to Month 48 in CRP levels
Time frame: Up to Month 48
Population: Non responder imputation population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABX464 Treatment Arm | CRP Levels | 2.29 mg/L | Standard Deviation 4.82 |
Secondary
Erythrocyte Sedimentation Rate (ESR) Levels
The change from Day 0 up to Month 48 in ESR levels
Time frame: up to 48 Months
Population: Non responder imputation population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABX464 Treatment Arm | Erythrocyte Sedimentation Rate (ESR) Levels | 2.90 mm/hour | Standard Deviation 8.62 |
Secondary
Fecal Calprotectin
The change from Day 0 up to Month 48 in fecal calprotectin A higher (in negative) change shows a better efficacy
Time frame: Up to Month 48
Population: Non responder imputation population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABX464 Treatment Arm | Fecal Calprotectin | -299.69 ug/g | Standard Deviation 472.28 |
Secondary
Number of Adverse Events Leading to Investigational Product Discontinuation
The number of incidences of adverse events leading to investigational product discontinuation
Time frame: Through subject study treatment, up to 48 months
Population: Observed cases population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABX464 Treatment Arm | Number of Adverse Events Leading to Investigational Product Discontinuation | 1 event |
Secondary
Number of Specific Laboratory Abnormalities
The number of incidences of specific laboratory abnormalities
Time frame: Through first year of subject study treatment, 12 months
Population: Observed Cases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABX464 Treatment Arm | Number of Specific Laboratory Abnormalities | 17 events |
Secondary
Number of Subjects With Clinical Remission at Month 48
Clinical remission was achieved when all the following criteria were met in the components of the Mayo clinical Score: rectal bleeding sub-score = 0 central endoscopy sub-score \<= 1 stool frequency sub-score \<= 1
Time frame: up to 48 months
Population: non responder imputation population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ABX464 Treatment Arm | Number of Subjects With Clinical Remission at Month 48 | 9 Participants |
Secondary
Number of Subjects With Clinical Response at Month 48
Clinical response was defined as: reduction in Total Mayo Score (TMS) of at least 2 points and \>= 30 percent from baseline with an accompanying decrease in rectal bleeding sub-score of \>= 1 point or absolute rectal bleeding sub-score of \<= 1 point.
Time frame: up to 48 months
Population: Non responder imputation population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ABX464 Treatment Arm | Number of Subjects With Clinical Response at Month 48 | 11 Participants |
Secondary
Number of Subjects With Endoscopic Remission at Month 48
Endoscopic remission was defined as Mayo central endoscopic sub-score = 0
Time frame: up to 48 months
Population: non responder imputation population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ABX464 Treatment Arm | Number of Subjects With Endoscopic Remission at Month 48 | 6 Participants |
Secondary
Number of Subject With Endoscopic Improvement at Month 48
oEndoscopic improvement was achieved if the Mayo central endoscopic sub-score is 0 or 1.
Time frame: up to 48 Months
Population: Non responder imputation population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ABX464 Treatment Arm | Number of Subject With Endoscopic Improvement at Month 48 | 9 Participants |
Secondary
Number of Treatment-emergent Adverse Events of Special Interest
The number of incidences of treatment-emergent adverse events of special interest
Time frame: Through subject study treatment, up to 48 months
Population: Observed cases population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABX464 Treatment Arm | Number of Treatment-emergent Adverse Events of Special Interest | 15 events |
Secondary
Number of Treatment-emergent Serious Adverse Events
The number of incidences of treatment-emergent serious adverse events
Time frame: Through subject study treatment, up to 48 months
Population: Observed cases population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABX464 Treatment Arm | Number of Treatment-emergent Serious Adverse Events | 3 events |
Secondary
Partial Mayo Score
The change from Day 0 up to Month 48 in Partial Mayo Score; Partial Mayo score is an index and consists of 3 items: stool frequency, rectal bleeding and a physician global assessment of disease activity. Each parameter of the score ranges from zero (normal or inactive disease) to 3 (severe activity). The partial mayo score scale ranging is from 0 to 9. A higher (in negative) change from baseline shows a better clinical response
Time frame: Up to Month 48
Population: Non responder imputation population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABX464 Treatment Arm | Partial Mayo Score | -2.2 units on a scale | Standard Deviation 2.4 |
Secondary
SF-36 Quality of Life Questionnaire (SF-36 Mental Component)
Change from Day 0 up to 24 months in SF-36 Questionnaire scores; The SF-36 questionnaire is a self-administered questionnaire containing 36 items. It measures health on eight multi-item dimensions, covering functional status, well-being, and overall evaluation of health. These items are grouped in 2 distincts components: a physical component (SF-36 physical) and a mental component (SF-36 mental). This outcome describes the SF-36 mental component. Each item score ranging is from 0 to 100. A higher positive value in change indicate a better health status. The higher the change from baseline, the better improvement
Time frame: Up to 24 months
Population: Non responder imputation population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABX464 Treatment Arm | SF-36 Quality of Life Questionnaire (SF-36 Mental Component) | 6.38 units on a scale | Standard Deviation 3.4 |
Secondary
SF-36 Quality of Life Questionnaire (SF-36 Physical Component)
Change from Day 0 up to 24 months in SF-36 Questionnaire scores; The SF-36 questionnaire is a self-administered questionnaire containing 36 items. It measures health on eight multi-item dimensions, covering functional status, well-being, and overall evaluation of health. These items are grouped in 2 distincts components: a physical component (SF-36 physical) and a mental component (SF-36 mental). This outcome describes the SF-36 physical component. Each item score ranging is from 0 to 100. A higher positive value in change indicate a better health status. The higher the change from baseline, the better improvement
Time frame: Up to 24 months
Population: Non responder imputation population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABX464 Treatment Arm | SF-36 Quality of Life Questionnaire (SF-36 Physical Component) | 4.82 units on a scale | Standard Deviation 4.23 |
Secondary
Total Mayo Score
The change from Day 0 up to Month 48 in Total Mayo Score. total mayo score is an index and consists of 4 items: stool frequency, rectal bleeding, flexible sigmoidoscopic examination, and a physician global assessment of disease activity. Each parameter of the score ranges from zero (normal or inactive disease) to 3 (severe activity). The total mayo score scale ranging is from 0 to 12 The change from baseline of this score is part of the clinical response definition: to get a clinical response, a reduction in Total Mayo score of at least 2 points is required. A higher (in negative) change shows a better clinical response.
Time frame: Up to Month 48
Population: Non responder Imputation (NRI) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABX464 Treatment Arm | Total Mayo Score | -3.0 units on a scale | Standard Deviation 3.4 |
Post Hoc
UC Worsening
Proportion of subjects with UC worsening based on adverse events
Time frame: Up to Month 48
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ABX464 Treatment Arm | UC Worsening | 7 Participants |