Progressive Familial Intrahepatic Cholestasis (PFIC)
Conditions
Keywords
Cholestasis, Maralixibat, Mutation, PFIC, PFIC2, Bile Duct Diseases, Liver Diseases, Biliary Tract Diseases, Digestive System Diseases, Pediatric
Brief summary
The primary objective of this open label extension study is to evaluate the long-term safety and tolerability of maralixibat.
Detailed description
The study will be conducted at multiple sites in North America, Europe, Asia, and South America.
Interventions
DRUGMaralixibat
All subjects will receive Maralixibat oral solution (up to 600 microgram per kilogram \[mcg/kg\]) twice daily
Sponsors
Mirum Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Provide informed consent and assent (as applicable) per Institutional Review Board/Ethics Committee (IRB/EC) 2. Completion of study MRX-502
Exclusion criteria
1. Any female who is pregnant or lactating or who is planning to become pregnant 2. Administration of prohibited medication between the MRX-502 EOT visit and the MRX 503 Baseline Visit (Day 0) 3. History of non-compliance in study MRX-502, non-adherence to medical regimens, unreliability, mental instability or incompetence that could compromise the validity of informed consent or lead to non-adherence with the study protocol based on Investigator judgment 4. Experienced an adverse event (AE) or serious adverse event (SAE) related to maralixibat during the MRX-502 study that led to permanent discontinuation of the subject from maralixibat 5. Any other conditions or laboratory abnormalities that, in the opinion of the Investigator or Sponsor Medical Monitor, may compromise the safety of the subject, or interfere with the subject participating in or completing the study 6. Cognitive impairment of the subject or caregiver that would, in the opinion of the investigator, preclude appropriate understanding of study information and compliance with study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline Over Time in the Average Morning ItchRO(Obs) Severity Score | From Baseline to Weeks 75-78 | The Score on the ItchRo scale is a score on a 5-point scale from 0 (no itch) to 4 (very severe itch) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance of ItchRO(Obs) Response (Weeks 15 - 26) | Week 15 - 26 | Maintenance of treatment effect is defined as the proportion of participants in the MRX-MRX treatment group (MRX-502 and MRX-503 data for subjects on MRX in the MRX-502 study) who obtain an ItchRO (Obs) response from Week 15 to Week 26 in Study MRX-503 in the primary cohort and PFIC cohort. |
| Proportion of ItchRO(Obs) Responders Over Time | Baseline to EOT | Proportion of ItchRO responders over time at each study visit using the 4-week study period prior to the visit as per ItchRO(Obs) responder definition. |
| Mean Change From Baseline Over Time in the Average Morning ItchRO(Obs) Frequency Score | From Baseline to Weeks 75-78 | The Score on the ItchRo scale is a score on a 5-point scale from 0 (no itch) to 4 (very severe itch) |
| Mean Change From Baseline Over Time in Total Serum Bile Acid (sBA) Levels | Baseline to week 70 | Mean change from baseline over time in total serum bile acid (sBA) levels |
| Proportion of Subjects Who Experience an sBA Control Over Time From Week 18 to Week 26 | From Week 18 to Week 26 | Proportion of subjects who experience an sBA control over time from Week 18 to Week 26 |
| Change From Baseline in Height Z-score | From baseline to Week 70 | Height-for-age Z-score measures a participant's height relative to a reference population of children of the same age and sex. Z-scores were derived using World Health Organization growth charts for participants less than 24 months of age and Centers for Disease Control and Prevention growth charts for participants 24 months of age or older. A Z-score of 0 represents the population mean for age and sex. Positive Z-scores indicate height above the reference population mean, and negative Z-scores indicate height below the reference population mean. Higher Z-scores generally indicate greater linear growth relative to the reference population. Change from baseline was calculated as post-baseline height-for-age Z-score minus baseline height-for-age Z-score. |
| Change From Baseline in Weight Z-score | From Baseline to Week 70 | Weight-for-age Z-score measures a participant's weight relative to a reference population of children of the same age and sex. Z-scores were derived using World Health Organization growth charts for participants less than 24 months of age and Centers for Disease Control and Prevention growth charts for participants 24 months of age or older. A Z-score of 0 represents the population mean for age and sex. Positive Z-scores indicate weight above the reference population mean, and negative Z-scores indicate weight below the reference population mean. Higher Z-scores generally indicate greater body weight relative to the reference population. Change from baseline was calculated as post-baseline weight-for-age Z-score minus baseline weight-for-age Z-score. |
Countries
Argentina, Austria, Belgium, Brazil, Canada, Colombia, France, Germany, Italy, Lebanon, Mexico, Poland, Singapore, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
A total of 84 participants were enrolled at 28 sites across 16 countries (Argentina, Austria, Belgium, Brazil, Canada, Colombia, France, Germany, Italy, Lebanon, Mexico, Poland, Singapore, Turkey, United Kingdom, United States)
Pre-assignment details
MRX-503, screening starts after signing the ICF and confirming eligibility. It overlaps with the MRX-502 end-of-treatment (EOT) visit: if the MRX-503 baseline visit occurs the same day or within 30 days of the MRX-502 EOT visit, those prior evaluations count as the MRX-503 baseline assessments.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized Adolescents (12-17 years) | 4 Participants |
| Age, Customized Children (2-11 years) | 62 Participants |
| Age, Customized Infants and toddlers (28 days - 23 months) | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Region of Enrollment Argentina | 3 participants |
| Region of Enrollment Austria | 2 participants |
| Region of Enrollment Belgium | 2 participants |
| Region of Enrollment Brazil | 10 participants |
| Region of Enrollment Canada | 2 participants |
| Region of Enrollment Colombia | 5 participants |
| Region of Enrollment France | 3 participants |
| Region of Enrollment Germany | 2 participants |
| Region of Enrollment Italy | 5 participants |
| Region of Enrollment Lebanon | 13 participants |
| Region of Enrollment Mexico | 8 participants |
| Region of Enrollment Poland | 5 participants |
| Region of Enrollment Singapore | 2 participants |
| Region of Enrollment Turkey | 2 participants |
| Region of Enrollment United Kingdom | 2 participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 48 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 84 |
| other Total, other adverse events | 84 / 84 |
| serious Total, serious adverse events | 25 / 84 |
Outcome results
None listed