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Also known as LUM001 (Maralixibat), Maralixibat
LUM001 · 15 trials · 10 indications
ItchRO(Obs) severity score = Itch Reported Outcome Observer assessment severity score; scale between 0 (not itchy at all) and 4 (extremely itchy); the lower the score the better.
The Score on the ItchRo scale is a score on a 5-point scale from 0 (no itch) to 4 (very severe itch)
The primary efficacy endpoint is the mean change in the average morning ItchRO(Obs) severity score between baseline and Weeks 15-26, using 4-week average morning ItchRO(Obs) severity scores (Mixed Model Repeated Measures). The baseline average morning ItchRO(Obs) severity score is defined as the 4-week average morning ItchRO(Obs) severity score prior to the first dose of the study medication. ItchRo(Obs) Severity Score = Itch Reported Outcome Observer assessment severity score; scale between 0 (not itchy at all) and 4 (extremely itchy); the lower the score the better.
TEAEs = Treatment-emergent Adverse Events
TEAE = Treatment-emergent Adverse Event; AESI = Adverse Event of Special Interest..
This primacy efficacy endpoint is the mean change from MRX baseline to week 48 in fasting sBA levels.
Pruritus was assessed using Itch report outcome measure (ItchRO\[Obs\]), administered as an electronic diary (eDiary) which was completed by the participants twice daily (morning and evening). ItchRO(Obs) score ranged from 0 to 4, with the higher score indicating increasing itch severity. The highest score between the morning and evening ItchRO(Obs) reports represented the daily score: a measure of the worst itching over the previous 24-hour period.
The primary efficacy endpoint of this study was the mean change from Week 18 to Week 22 (the RWD period) of fasting sBA levels in participants who had a reduction in sBA ≥50% from baseline to Week 12 or Week 18 (Modified Intent-to-Treat \[MITT\] Population). Five participants in the MRX group and 10 participants in the placebo group met the prespecified sBA reduction criteria.
An Adverse Event (AE) was defined as any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered to be related to the investigational drug product. TEAEs were AEs with a start date on or after the first dose of investigational product and started prior to the last dose of investigational product plus 14 days.
Serum bile acid levels were evaluated using blood samples collected.
The primary endpoint of this study was the mean change from MRX baseline to Week 48 in fasting sBA level.
Participants were required to fast for at least 4 hours; only water was permitted prior to collection. A negative change from baseline indicates that the level of bile acid decreased.
Pruritus was assessed using ItchRO measure, administered as an electronic diary (eDiary) which was completed by the participants twice daily (morning and evening). (ItchRO) scores ranged from 0 to 10, with 0 representing no itch and 10 representing very severe itching. The highest score between the morning and evening ItchRO reports represented the daily score: a measure of the worst itching over the previous 24-hour period. The weekly sum score was calculated as the sum of the daily scores for the 7 days prior to the time point being reported: 7 days prior to randomization or 7 days prior to Week 13/ET visit.
| Arm | Type | Description |
|---|---|---|
| Maralixibat | EXPERIMENTAL | Participants will receive maralixibat oral solution 300 μg/kg orally once daily for 1 week and then twice daily for 39 weeks. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo matched to maralixibat oral solution orally once daily for 1 week and then twice daily for 19 weeks. After 20 weeks, participants will receive maralixibat oral solution 300 μg/kg orally once daily for 1 week and then twice daily for 19 weeks. |
| Maralixibat Treatment | EXPERIMENTAL | Participants will receive maralixibat tablets or oral solution. |
| Double Blind - Maralixibat | EXPERIMENTAL | The double-blind period comprised of 4-8 weeks of dose escalation followed by 18 - 22 weeks of stable dosing treatment, after which participants were transferred to the open-label arm. |
| Double Blind - Placebo | PLACEBO_COMPARATOR | The double-blind period comprised of 4-8 weeks of dose escalation followed by 18 - 22 weeks of stable dosing treatment, after which participants were transferred to the open-label arm. |
| Open Label - Maralixibat | EXPERIMENTAL | The Open-Label period comprised of 4-8 weeks of dose escalation followed by 70 - 74 weeks of stable dosing treatment. During the OLE, all participants, regardless of treatment assignment in the double-blind period, received maralixibat. |
| LUM001 (Maralixibat) | EXPERIMENTAL | Participant will receive LUM001 also known as Maralixibat (MRX) administered orally once per day. |
| LUM001 | EXPERIMENTAL | LUM001 for oral administration |
| LUM001 and Ursodeoxycholic Acid (UDCA) | EXPERIMENTAL | Administered orally once daily |
| Placebo and Ursodeoxycholic Acid (UDCA) | PLACEBO_COMPARATOR | Administered orally once daily |
| Name | Type | Description |
|---|---|---|
| Maralixibat | DRUG | Maralixibat will be provided as an oral solution along with 0.5-, 1.0-, and 3.0-mL sized dosing dispensers. During the double-blind dose escalation period (4 weeks), the study drug (maralixibat) will be administered once daily for 1 week and then twice daily (BID; morning and evening). During the double-blind stable dosing period (16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the double-blind dose-escalation period) of maralixibat. During the open-label dose escalation period (4 weeks), all participants will receive maralixibat treatment once daily for 1 week and then twice daily (BID; morning and evening). During the open-label stable dosing period (at least 16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the open-label dose-escalation period) of maralixibat. |
| Placebo | OTHER | Placebo matched to maralixibat will be provided as an oral solution along with 0.5-, 1.0-, and 3.0-mL sized dosing dispensers. During the double-blind dose escalation period (4 weeks), study drug will be administered once daily for 1 week and then twice daily (BID; morning and evening). During the double-blind stable dosing period (16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the double-blind dose-escalation period) of study drug. During the open-label dose escalation period (4 weeks), all participants will receive maralixibat treatment once daily for 1 week and then twice daily (BID; morning and evening). During the open-label stable dosing period (16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the open-label dose-escalation period) of maralixibat. |
| LUM001 (Maralixibat) | DRUG | Dosing of LUM001 also known as Maralixibat (MRX) with the objective of achieving optimal control of pruritus at a dose level that is tolerated by the participant and up to a maximum daily dose of 280 micrograms per kilogram (mcg/kg). |
| LUM001 | DRUG | LUM001 administered orally |
| Ursodeoxycholic Acid | DRUG | - |
Inclusion Criteria: 1. Informed consent and assent (as applicable) 2. Age ≥6 months at time of baseline visit 3. Diagnosis of a rare cholestatic liver disease with cholestatic pruritus based on the following: 1. Chronic liver biochemical abnormalities (\>90 days) and/or pathological evidence of...
LUM001 is an investigational small molecule studied in rare cholestatic liver diseases. Its Phase 2 program covered Alagille Syndrome, primary biliary cholangitis, primary sclerosing cholangitis, and progressive familial intrahepatic cholestasis. It is not approved for any indication and remains in clinical development.
LUM001 is developed by Mirum Pharmaceuticals, Inc., which trades on the Nasdaq under the ticker MIRM. The company ran the Phase 2 program across the cholestatic liver disease indications associated with the asset.
LUM001 is in Phase 2 development. Five Phase 2 trials have been completed, including randomized, double-blind, placebo-controlled studies, and no trials are currently listed as active. It is an investigational agent and is not approved by the FDA.
Five completed Phase 2 trials studied LUM001. These include NCT02160782 and the extension study NCT02117713 in Alagille Syndrome, NCT02061540 in primary sclerosing cholangitis, and NCT02057718 in progressive familial intrahepatic cholestasis. Total enrollment across the program was 141 participants.
Yes, LUM001 is also known as maralixibat. The two names refer to the same investigational small molecule, and the Phase 2 trial titles use both designations interchangeably, including the Alagille Syndrome and progressive familial intrahepatic cholestasis studies.
LUM001 was studied in Alagille Syndrome as a treatment for cholestatic liver disease in pediatric patients. Two completed Phase 2 trials enrolled children from 12 months of age, one of which was a randomized, double-blind, placebo-controlled study with a drug withdrawal period, plus a long-term extension study.