Phase 2
N=31
Safety and Efficacy Study of LUM001 (Maralixibat) With a Drug Withdrawal Period in Participants With Alagille Syndrome (ALGS)
Alagille Syndrome
Bottom Line
View on ClinicalTrials.gov: NCT02160782 ↗Enrolled (actual)
31
Serious AEs
21.0%
Results posted
Jul 2021
Primary outcome: Primary: Change From Week 18 to Week 22 in Fasting sBA Levels in Participants Who Had a Reduction in sBA ≥50% From Baseline to Week 12 or Week 18 — -21.73; 95.55 μmol/L — p=0.0464
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- LUM001 (Maralixibat) (Drug); Placebo (Drug)
- Age
- Pediatric, Adult · 0+ yrs
- Sex
- All
- Sponsor
- Mirum Pharmaceuticals, Inc.
- Primary completion
- May 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Week 18 to Week 22 in Fasting sBA Levels in Participants Who Had a Reduction in sBA ≥50% From Baseline to Week 12 or Week 18 |
-21.73; 95.55 | 0.0464 sig |
| SECONDARY Change From Baseline to Week 18 in Fasting sBA Levels |
283.43; 192.50 | 0.0005 sig |
| SECONDARY Change From Baseline to Week 18 in Pruritus as Measured by ItchRO (Obs) |
2.909; 1.203 | < 0.0001 sig |
| SECONDARY Change From Baseline to Week 18 in Pruritus as Measured by ItchRO (Pt) |
2.903; 0.831 | < 0.0001 sig |
| SECONDARY Change From Week 18 to Week 22 in Pruritus as Measured by ItchRO(Obs) |
0.217; 1.700 | < 0.0001 sig |
| SECONDARY Change From Week 18 to Week 22 in Pruritus as Measured by ItchRO(Pt) |
-0.149; 1.839 | 0.0013 sig |
| SECONDARY Change From Baseline to Week 18 in Alkaline Phosphatase |
601.3; 580.8 | 0.2163 |
| SECONDARY Change From Week 18 to Week 22 in Alkaline Phosphatase |
2.8; -7.2 | 0.7455 |
| SECONDARY Change From Baseline to Week 18 in Alanine Aminotransferase |
181.0; 177.4 | 0.9358 |
| SECONDARY Change From Week 18 to Week 22 in Alanine Aminotransferase |
34.5; 19.4 | 0.4472 |
| SECONDARY Change From Baseline to Week 18 in Total Bilirubin |
6.09; 5.12 | 0.0893 |
| SECONDARY Change From Week 18 to Week 22 in Total Bilirubin |
0.32; 0.46 | 0.7 |
| SECONDARY Change From Baseline to Week 18 in Direct Bilirubin |
4.57; 3.98 | 0.0139 sig |
| SECONDARY Change From Week 18 to Week 22 in Direct Bilirubin |
0.13; 0.14 | 0.9517 |
Summary
This is a long-term, open-label study with a double-blind, placebo-controlled, randomized drug withdrawal period in children with Alagille Syndrome (ALGS) designed to evaluate the safety and efficacy of LUM001 (Also known as maralixibat or MRX).
Eligibility Criteria
Inclusion Criteria
- Male or female between the ages of 12 months and 18 years inclusive.
- Diagnosis of ALGS.
- Evidence of cholestasis (one or more of the following):
- Total serum bile acid > 3x ULN for age.
- Conjugated bilirubin > 1 mg/dL.
- Fat soluble vitamin deficiency otherwise unexplainable.
- GGT > 3x ULN for age.
- Intractable pruritus explainable only by liver disease.
- Females of childbearing potential must have a negative serum pregnancy test during Screening.
- Males and females of child-bearing potential who are sexually active, or are not currently sexually active during the study, but become sexually active during the period of the study and 30 days following the last dose of study drug, must agree and use acceptable contraception during the trial.
- Participant is expected to have a consistent caregiver(s) for the duration of the study.
- Informed consent and assent (per IRB/IEC) as appropriate.
- Access to phone for scheduled calls from study site.
- Caregivers (and age-appropriate participants) must be willing and able to use an eDiary device during the study.
- Caregivers (and age-appropriate participants) must digitally accept the licensing agreement in the eDiary software.
- Caregivers (and age-appropriate participants) must complete at least 10 eDiary reports (morning or evening) during each of two consecutive weeks of the screening period (maximum possible reports = 14 per week).
- Average daily score >2 on the Itch Reported Outcome (ItchRO™) questionnaire (maximum possible daily score of 4) for two consecutive weeks in the screening period, prior to dosing. A daily score is the higher of the scores for the morning and evening ItchRO. The average daily score is the sum of all daily scores divided by the number of days the ItchRO was completed.
Inclusion Criteria for participants to be eligible for the 52-week optional follow-up treatment period:
- Completed the protocol through the Week 48 visit with no safety concerns. Participants who were discontinued due to safety reasons can be rechallenged if blood tests are back to relatively normal values for this patient population and participant does not meet any of the protocol's stopping rules. The decision will be made by the investigator in consultation with the sponsor medical monitor.
- Participants who have undergone a surgical disruption of the enterohepatic circulation will not be eligible to enter into the follow up treatment period.
- Participants who were discontinued for other reasons will be considered for the 52-week optional follow-up treatment period on an individual basis. The decision will be made by the investigator in consultation with the sponsor medical monitor.
Inclusion Criteria for participants with LUM001dosing interruption =7 days:
- The Participant has either: completed the protocol through the Week 48 visit with no major safety concerns OR discontinued due to safety reasons judged unrelated to the study drug, and laboratory results have returned to levels acceptable for this patient population or individual and participant does not meet any of the protocol's stopping rules at the time of entry into the follow-up period. The decision will be made by the investigator in consultation with the sponsor medical monitor. [Participants who were discontinued for other reasons will be considered on an individual basis.]
- Females of childbearing potential must have a negative urine or serum pregnancy test (beta- human chorionic gonadotropin [β-hCG]) at the time of entry into the long-term optional follow-up treatment period.
- Males and females of child-bearing potential who are sexually active, or are not currently sexually active during the study, but become sexually active during the period of the study and 30 days following the last dose of study drug, must agree and use acceptable contraception during the trial.
- Informed consent and assent (per IRB/EC) as appropriate.
- Access to phone for scheduled calls from study
Data sourced from ClinicalTrials.gov (NCT02160782). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.