Alagille Syndrome
Conditions
Keywords
ALGS, Alagille syndrome
Brief summary
Double-blind, randomized, placebo-controlled, Phase 3 study to investigate the efficacy and safety of odevixibat compared to placebo in Patients with Alagille Syndrome.
Detailed description
Approximately 35 sites will be initiated for this study in North America, Europe, Middle East, and Asia Pacific.
Interventions
DRUGOdevixibat
Odevixibat is a small molecule and selective inhibitor of IBAT.
DRUGPlacebo
Placebo identical in appearance to experimental drug (odevixibat).
Sponsors
Albireo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Genetically confirmed diagnosis of Alagille syndrome * History of significant pruritus as measured by the Albireo Observer or Patient Reported Outcome instrument * Elevated serum bile acid level Key
Exclusion criteria
* History or ongoing presence of other types of liver disease (eg. biliary atresia, progressive familial intrahepatic cholestasis, hepatocellular carcinoma) * History of liver transplant, or a liver transplant is planned within 6 months of randomization * ALT \>10× upper limit of normal (ULN) at screening * Total bilirubin \>15 × ULN at screening * Patient suffers from uncontrolled, recalcitrant pruritic condition other than Alagille syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Scratching Score | Change from baseline for each four-week average pruritis score to Month 6 (Weeks 21 to 24), in which baseline was calculated based on the 14 days before the start of treatment. | Change from baseline in average AM (measured after waking up) and PM (measured before bedtime) scratching score to Month 6 as measured by the Albireo Observer-Reported Outcome (ObsRO) Instrument. The ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with scores from 0 to 4 where 0 is no scratching and 4 is worst possible scratching. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Bile Acid Levels | Change from baseline to average of week 20 and 24, where baseline was calculated by averaging the last two values preceding start of treatment, and average of Week 20 and Week 24 was defined as the average of Week 20 and Week 24 values. | Change in serum bile acid levels (μmol/L) from baseline to average of week 20 and 24 |
Countries
Belgium, Canada, France, Germany, Israel, Italy, Malaysia, Netherlands, New Zealand, Poland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Odevixibat (A4250) Capsules for oral administration once daily for 24 weeks (120 μg/kg/day).
Odevixibat: Odevixibat is a small molecule and selective inhibitor of IBAT. | 35 |
| Placebo Capsules for oral administration (to match active) once daily for 24 weeks.
Placebo: Placebo identical in appearance to experimental drug (odevixibat). | 17 |
| Total | 52 |
Baseline characteristics
| Characteristic | Odevixibat (A4250) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 35 Participants | 17 Participants | 52 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 6.73 years STANDARD_DEVIATION 3.78 | 5.40 years STANDARD_DEVIATION 4.411 | 6.29 years STANDARD_DEVIATION 4.003 |
| Age, Customized < 10 years | 29 Participants | 13 Participants | 42 Participants |
| Age, Customized > = 10 years and < 18 years | 6 Participants | 4 Participants | 10 Participants |
| Genetic Mutation JAG1 | 32 Participants | 16 Participants | 48 Participants |
| Genetic Mutation NOTCH2 | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 30 Participants | 13 Participants | 43 Participants |
| Region of Enrollment Belgium | 1 participants | 1 participants | 2 participants |
| Region of Enrollment France | 3 participants | 1 participants | 4 participants |
| Region of Enrollment Germany | 6 participants | 2 participants | 8 participants |
| Region of Enrollment Italy | 4 participants | 2 participants | 6 participants |
| Region of Enrollment Malaysia | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Netherlands | 3 participants | 3 participants | 6 participants |
| Region of Enrollment Poland | 7 participants | 3 participants | 10 participants |
| Region of Enrollment Turkey | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United Kingdom | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 7 participants | 4 participants | 11 participants |
| Sex: Female, Male Female | 14 Participants | 11 Participants | 25 Participants |
| Sex: Female, Male Male | 21 Participants | 6 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 17 |
| other Total, other adverse events | 26 / 35 | 12 / 17 |
| serious Total, serious adverse events | 5 / 35 | 2 / 17 |
Outcome results
Primary
Change From Baseline in Scratching Score
Change from baseline in average AM (measured after waking up) and PM (measured before bedtime) scratching score to Month 6 as measured by the Albireo Observer-Reported Outcome (ObsRO) Instrument. The ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with scores from 0 to 4 where 0 is no scratching and 4 is worst possible scratching.
Time frame: Change from baseline for each four-week average pruritis score to Month 6 (Weeks 21 to 24), in which baseline was calculated based on the 14 days before the start of treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Odevixibat (A4250) | Change From Baseline in Scratching Score | -1.69 score on a scale | Standard Error 0.174 |
| Placebo | Change From Baseline in Scratching Score | -0.8 score on a scale | Standard Error 0.233 |
Comparison: The analysis is based on a mixed model for repeated measures (MMRM) using a restricted maximum likelihood (REML) with baseline score as a covariate, and baseline age stratification, baseline direct bilirubin, treatment group, time (in months), and treatment-by-time interaction as fixed effects. One-sided p-value was reported.p-value: 0.001295% CI: [-1.44, -0.33]Mixed Models Analysis
Secondary
Serum Bile Acid Levels
Change in serum bile acid levels (μmol/L) from baseline to average of week 20 and 24
Time frame: Change from baseline to average of week 20 and 24, where baseline was calculated by averaging the last two values preceding start of treatment, and average of Week 20 and Week 24 was defined as the average of Week 20 and Week 24 values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Odevixibat (A4250) | Serum Bile Acid Levels | -90.35 μmol/L | Standard Error 21.336 |
| Placebo | Serum Bile Acid Levels | 22.39 μmol/L | Standard Error 28.463 |
Comparison: The analysis is based on a mixed model for repeated measures (MMRM) using a restricted maximum likelihood (REML) with baseline serum bile acid (sBA) concentration data as a covariate, and baseline age stratification, treatment group, visits (Weeks 4, 8, 12, 16, 20, 24), and treatment-by-visit interaction as fixed effects. The comparison of treatment difference in change from baseline to the average of Week 20 and Week 24 is estimated and tested using contrast. One-sided p-value was reported.p-value: 0.000695% CI: [-178.78, -46.69]Mixed Models Analysis