Alagille Syndrome
Conditions
Brief summary
The purpose of this extension study is to determine the long-term safety and tolerability of an investigational treatment (LUM001 also known as Maralixibat) in children with ALGS who have completed participation in a core LUM001 treatment protocol. Efficacy will be assessed by evaluating the effect of LUM001 on pruritus, biochemical markers of pruritus, as well as biochemical markers of cholestasis and liver disease.
Interventions
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 560 micrograms per kilogram (mcg/kg).
Sponsors
Mirum Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
Participation for an individual patient is expected to be approximately 72 weeks. Patients who complete 72 weeks of treatment may be eligible to receive treatment for up to 52 weeks during the follow-up treatment period and patients who completed the 124 weeks of treatment may be eligible to enter the additional long-term follow-up period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From MRX Baseline to Week 48 in Fasting sBA Levels | MRX baseline to Week 48 | The primary endpoint of this study was the mean change from MRX baseline to Week 48 in fasting sBA level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From MRX Baseline to Week 48 in Pruritus | MRX baseline to Week 48 | This secondary efficacy endpoint is the change from MRX baseline to Week 48 in pruritus as measured by ItchRO(Obs) weekly average morning severity score. ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe). |
| Change From MRX Baseline Over Time in Pruritus | MRX baseline to End of Treatment (maximum exposure was 336 weeks) | This secondary efficacy endpoint is the change from MRX baseline over time in pruritus as measured by ItchRO(Obs) weekly average morning severity score. ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe). Results reported here are the long-term results. |
| Change From MRX Baseline Over Time in Alkaline Phosphatase | MRX baseline to end of treatment (maximum exposure was 336 weeks) | This secondary efficacy endpoint is the mean change from MRX baseline over time in ALP. Results reported here are the long-term results. |
| Change From MRX Baseline to Week 48 in Alanine Aminotransferase | MRX baseline to Week 48 | This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALT. |
| Change From MRX Baseline to Week 48 in Clinician Xanthoma Severity Score | MRX baseline to Week 48 | This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in clinician xanthoma severity scores. It is based on a 0-4 scale to rate the number of lesions present and the degree to which the participant's lesions interfere or limit his or her activities. Clinician xanthoma severity scores range from 0 to 4, with a xanthoma score of zero representing no evidence of xanthomatosis and a score of 4 representing xanthoma so severe that it is disabling. Clinician xanthoma severity scores were not assessed in Study LUM001-302 so mean clinician xanthoma severity score at MRX baseline was calculated from the 5 participants who were assigned to placebo in Study LUM001-302, and analysis of change from MRX baseline is not presented. |
| Change From MRX Baseline Over Time in Clinician Xanthoma Severity Score | MRX baseline to End of Treatment (maximum exposure was 336 weeks) | This secondary efficacy endpoint is the mean change from MRX baseline over time (with Week 252 chosen as the end point, as the last analysis visit with at least 6 participants) in clinician xanthoma severity scores. It is based on a 0-4 scale to rate the number of lesions present and the degree to which the lesions interfere or limit activities. Clinician xanthoma severity scores range from 0 to 4, with a score of zero representing no evidence of xanthomatosis and a score of 4 representing xanthoma so severe that it is disabling. Clinician xanthoma severity scores were not assessed in Study LUM001-302 so mean clinician xanthoma severity score at MRX baseline was calculated from the 5 participants assigned to placebo in Study LUM001-302, and analysis of change from MRX baseline is not presented. Results reported here are the long-term results. |
| Secondary: Change From MRX Baseline to Week 48 in Alkaline Phosphatase | MRX baseline to Week 48 | This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALP. |
| Change From MRX Baseline Over Time in Fasting sBA Levels | MRX baseline to End of Treatment (maximum exposure was 336 weeks) | This secondary efficacy endpoint is the mean change from MRX baseline over time in fasting sBA levels. Results reported here are the long-term results. |
| Change From MRX Baseline Over Time in Alanine Aminotransferase | MRX baseline to End of Treatment (maximum exposure was 336 weeks) | This secondary efficacy endpoint is the mean change from MRX baseline over time in ALT levels. Results reported here are the long-term results. |
| Change From MRX Baseline to Week 48 in Aspartate Aminotransferase | MRX baseline to Week 48 | This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in AST levels. |
| Change From MRX Baseline Over Time in Aspartate Aminotransferase | MRX baseline to End of treatment (maximum exposure was 336 weeks) | This secondary efficacy endpoint is the mean change from MRX baseline over time in AST levels. Results reported here are the long-term results. |
| Change From MRX Baseline to Week 48 in Gamma Glutamyltransferase | MRX baseline to Week 48 | This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in GGT. |
| Change From MRX Baseline Over Time in Gamma Glutamyltransferase | MRX baseline to End of Treatment (maximum exposure was 336 weeks) | This secondary efficacy endpoint is the mean change from MRX baseline over time in GGT. Results reported here are the long-term results. |
| Change From MRX Baseline Over Time in Total and Direct Bilirubin | MRX baseline to End of Treatment (maximum exposure was 336 weeks) | This secondary efficacy endpoint is the mean change from MRX baseline over time in total bilirubin and direct bilirubin. Results reported here are the long-term results. |
| Change From MRX Baseline to Week 48 in Total and Direct Bilirubin | MRX baseline to Week 48 | This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in total bilirubin and direct bilirubin. |
Countries
United Kingdom
Participant flow
Pre-assignment details
All participants within the study were enrolled from the lead-in Study LUM001-302, where they received various doses of maralixibat (LUM001, MRX) or placebo. Within this study, after a short dose escalation period, participants received MRX 280 ug/kg/day, which consisted of the majority of their exposure within the study. As such, summaries are presented as a single arm, MRX.
Participants by arm
| Arm | Count |
|---|---|
| Core Study Period In the lead-in Study LUM001-302, participants were randomized to receive either placebo or active drug (MRX). The last observation obtained before first dose of MRX (either for participants who received MRX in Study LUM001-302 or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302. The core study period of Study LUM001-303 was from Day 1 to Week 72. It encompassed: - a 4-week double-blind dose-escalation period - an 8-week dose-optimization period - a 60-week stable dosing period. Participants could consent to continued long-term follow-up. The furthest analysis timepoint reached by any participant was Week 336. All participants received MRX. | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Core Study Period | Adverse Event | 1 |
| Core Study Period | Did not consent to 52-week follow- up | 8 |
| Core Study Period | Withdrawal by caregiver | 3 |
| Long-term Follow-up Treatment Period | consent withdrawn by subject | 1 |
Baseline characteristics
| Characteristic | Core Study Period |
|---|---|
| Age, Customized 13 to 18 years | 3 Subjects |
| Age, Customized 2 to 4 years | 6 Subjects |
| Age, Customized <2 years | 3 Subjects |
| Age, Customized 5 to 8 years | 5 Subjects |
| Age, Customized 9 to 12 years | 2 Subjects |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 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 | 16 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 10 | 0 / 10 | 0 / 13 | 0 / 19 | 0 / 5 | 0 / 5 | 0 / 19 |
| other Total, other adverse events | 3 / 6 | 6 / 10 | 3 / 10 | 10 / 13 | 18 / 19 | 3 / 5 | 5 / 5 | 18 / 19 |
| serious Total, serious adverse events | 0 / 6 | 0 / 10 | 1 / 10 | 0 / 13 | 6 / 19 | 0 / 5 | 1 / 5 | 6 / 19 |
Outcome results
Primary
Change From MRX Baseline to Week 48 in Fasting sBA Levels
The primary endpoint of this study was the mean change from MRX baseline to Week 48 in fasting sBA level.
Time frame: MRX baseline to Week 48
Population: Data collected from 19 participants at MRX baseline. Data collected at Week 48 from 17 of the 19 participants who contributed values at MRX baseline.~Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline to Week 48 in Fasting sBA Levels | 261.96 μmol/L | Standard Deviation 206.839 |
| Core Study Period: Week 48 Values | Change From MRX Baseline to Week 48 in Fasting sBA Levels | 128.32 μmol/L | Standard Deviation 101.742 |
Comparison: This analysis investigated whether a statistically significant change in sBA levels was observed when comparing MRX baseline to Week 48. The analysis was based on the safety population.p-value: 0.001295% CI: [-145.26, -43.55]Student's t-test
Secondary
Change From MRX Baseline Over Time in Alanine Aminotransferase
This secondary efficacy endpoint is the mean change from MRX baseline over time in ALT levels. Results reported here are the long-term results.
Time frame: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Population: Data collected from 19 participants at MRX baseline. Data collected at Week 252 from all 6 participants who contributed values at MRX baseline. Week 252 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline Over Time in Alanine Aminotransferase | 130.7 U/L | Standard Deviation 59.12 |
| Core Study Period: Week 48 Values | Change From MRX Baseline Over Time in Alanine Aminotransferase | 175.3 U/L | Standard Deviation 101.17 |
Comparison: This analysis investigated whether a statistically significant change in ALT levels was observed over time (with Week 252 chosen as the end point, as the last analysis visit with at least 6 participants). The analysis was based on the safety population.p-value: 0.493495% CI: [-105, 189.7]Student's t-test
Secondary
Change From MRX Baseline Over Time in Alkaline Phosphatase
This secondary efficacy endpoint is the mean change from MRX baseline over time in ALP. Results reported here are the long-term results.
Time frame: MRX baseline to end of treatment (maximum exposure was 336 weeks)
Population: Data collected from 19 participants at MRX baseline. Data collected at Week 252 from 6 participants who contributed values at MRX baseline. Week 252 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline Over Time in Alkaline Phosphatase | 601.5 U/L | Standard Deviation 232.54 |
| Core Study Period: Week 48 Values | Change From MRX Baseline Over Time in Alkaline Phosphatase | 430.5 U/L | Standard Deviation 223.56 |
Comparison: This analysis investigated whether a statistically significant change in ALP levels was observed over time (with Week 252 chosen as the end point as the last analysis visit with at least 6 participants). The analysis was based on the safety population.p-value: 0.2295% CI: [-522.5, 153.8]Student's t-test
Secondary
Change From MRX Baseline Over Time in Aspartate Aminotransferase
This secondary efficacy endpoint is the mean change from MRX baseline over time in AST levels. Results reported here are the long-term results.
Time frame: MRX baseline to End of treatment (maximum exposure was 336 weeks)
Population: Data collected from 19 participants at MRX baseline. Data collected at Week 252 from 6 participants who contributed values at MRX baseline. Week 252 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline Over Time in Aspartate Aminotransferase | 127.6 U/L | Standard Deviation 60.03 |
| Core Study Period: Week 48 Values | Change From MRX Baseline Over Time in Aspartate Aminotransferase | 145.0 U/L | Standard Deviation 56.5 |
Comparison: This analysis investigated whether a statistically significant change in AST levels was observed over time (with Week 252 chosen as the end point as the last analysis visit with at least 6 participants). The analysis was based on the safety population.p-value: 0.781595% CI: [-94.7, 119]Student's t-test
Secondary
Change From MRX Baseline Over Time in Clinician Xanthoma Severity Score
This secondary efficacy endpoint is the mean change from MRX baseline over time (with Week 252 chosen as the end point, as the last analysis visit with at least 6 participants) in clinician xanthoma severity scores. It is based on a 0-4 scale to rate the number of lesions present and the degree to which the lesions interfere or limit activities. Clinician xanthoma severity scores range from 0 to 4, with a score of zero representing no evidence of xanthomatosis and a score of 4 representing xanthoma so severe that it is disabling. Clinician xanthoma severity scores were not assessed in Study LUM001-302 so mean clinician xanthoma severity score at MRX baseline was calculated from the 5 participants assigned to placebo in Study LUM001-302, and analysis of change from MRX baseline is not presented. Results reported here are the long-term results.
Time frame: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Population: Mean MRX baseline scores were calculated from the 5 participants assigned placebo in LUM001-302.Mean Week 252 scores were calculated from 6 participants. Week 252 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline Over Time in Clinician Xanthoma Severity Score | 0.4 scores on a scale | Standard Deviation 0.55 |
| Core Study Period: Week 48 Values | Change From MRX Baseline Over Time in Clinician Xanthoma Severity Score | 0.2 scores on a scale | Standard Deviation 0.41 |
Secondary
Change From MRX Baseline Over Time in Fasting sBA Levels
This secondary efficacy endpoint is the mean change from MRX baseline over time in fasting sBA levels. Results reported here are the long-term results.
Time frame: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Population: Data collected from 19 participants at MRX baseline. Data collected at Week 252 from all 6 participants who contributed values at MRX baseline. Week 252 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline Over Time in Fasting sBA Levels | 261.96 μmol/L | Standard Deviation 206.839 |
| Core Study Period: Week 48 Values | Change From MRX Baseline Over Time in Fasting sBA Levels | 118.32 μmol/L | Standard Deviation 76.14 |
Comparison: This analysis investigated whether a statistically significant change in sBA levels was observed over time (with Week 252 chosen as the end point, as the last analysis visit with at least 6 participants). The analysis was based on the safety population.p-value: 0.03295% CI: [-265.77, -18.12]Student's t-test
Secondary
Change From MRX Baseline Over Time in Gamma Glutamyltransferase
This secondary efficacy endpoint is the mean change from MRX baseline over time in GGT. Results reported here are the long-term results.
Time frame: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Population: Data collected from 19 participants at MRX baseline. Data collected at Week 252 from 6 participants who contributed values at MRX baseline. Week 252 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline Over Time in Gamma Glutamyltransferase | 476.9 U/L | Standard Deviation 376.85 |
| Core Study Period: Week 48 Values | Change From MRX Baseline Over Time in Gamma Glutamyltransferase | 377.5 U/L | Standard Deviation 163.1 |
Comparison: This analysis investigated whether a statistically significant change in GGT levels was observed over time (with Week 252 chosen as the end point as the last analysis visit with at least 6 participants). The analysis was based on the safety population.p-value: 0.713395% CI: [-431.2, 317.9]Student's t-test
Secondary
Change From MRX Baseline Over Time in Pruritus
This secondary efficacy endpoint is the change from MRX baseline over time in pruritus as measured by ItchRO(Obs) weekly average morning severity score. ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe). Results reported here are the long-term results.
Time frame: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Population: Data collected from 19 participants at MRX baseline Data collected at Week 278 from all 6 participants who contributed values at MRX baseline. Week 278 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline Over Time in Pruritus | 2.435 scores on a scale | Standard Deviation 0.7952 |
| Core Study Period: Week 48 Values | Change From MRX Baseline Over Time in Pruritus | 0.952 scores on a scale | Standard Deviation 0.4302 |
Comparison: This analysis investigated whether a statistically significant change in ItchRO(Obs) scores was observed over time (with Week 158 chosen as the end point, as the last analysis visit with at least 6 participants). The analysis was based on the safety population.p-value: 0.030795% CI: [-1.784, -0.132]Student's t-test
Secondary
Change From MRX Baseline Over Time in Total and Direct Bilirubin
This secondary efficacy endpoint is the mean change from MRX baseline over time in total bilirubin and direct bilirubin. Results reported here are the long-term results.
Time frame: MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Population: Data collected from 19 participants at MRX baseline. Data collected at Week 252 from 6 participants who contributed values at MRX baseline. Week 252 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline Over Time in Total and Direct Bilirubin | Total bilirubin | 4.47 mg/dL | Standard Deviation 4.837 |
| Core Study Period: MRX Baseline Values | Change From MRX Baseline Over Time in Total and Direct Bilirubin | Direct bilirubin | 3.80 mg/dL | Standard Deviation 3.858 |
| Core Study Period: Week 48 Values | Change From MRX Baseline Over Time in Total and Direct Bilirubin | Total bilirubin | 5.05 mg/dL | Standard Deviation 6.449 |
| Core Study Period: Week 48 Values | Change From MRX Baseline Over Time in Total and Direct Bilirubin | Direct bilirubin | 3.53 mg/dL | Standard Deviation 3.727 |
Comparison: This analysis investigated whether a statistically significant change in total bilirubin levels was observed over time (with Week 252 chosen as the end point as the last analysis visit with at least 6 participants). The analysis was based on the safety population.p-value: 0.821895% CI: [-6.31, 5.24]Student's t-test
Comparison: This analysis investigated whether a statistically significant change in direct bilirubin levels was observed over time (with Week 252 chosen as the end point as the last analysis visit with at least 6 participants). The analysis was based on the safety population.p-value: 0.554995% CI: [-2.62, 1.58]Student's t-test
Secondary
Change From MRX Baseline to Week 48 in Alanine Aminotransferase
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALT.
Time frame: MRX baseline to Week 48
Population: Data collected from 19 participants at MRX baseline. Data collected at Week 48 from 17 of the 19 participants who contributed values at MRX baseline. Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline to Week 48 in Alanine Aminotransferase | 130.7 U/L | Standard Deviation 59.12 |
| Core Study Period: Week 48 Values | Change From MRX Baseline to Week 48 in Alanine Aminotransferase | 174.5 U/L | Standard Deviation 97.28 |
Comparison: This analysis investigated whether a statistically significant change in ALT levels was observed when comparing MRX baseline to Week 48. The analysis was based on the safety population.p-value: 0.030795% CI: [5.4, 97.7]Student's t-test
Secondary
Change From MRX Baseline to Week 48 in Aspartate Aminotransferase
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in AST levels.
Time frame: MRX baseline to Week 48
Population: Data collected from 19 participants at MRX baseline. Data collected at Week 48 from 17 of the 19 participants who contributed values at MRX baseline. Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline to Week 48 in Aspartate Aminotransferase | 127.6 U/L | Standard Deviation 60.03 |
| Core Study Period: Week 48 Values | Change From MRX Baseline to Week 48 in Aspartate Aminotransferase | 142.4 U/L | Standard Deviation 78.94 |
Comparison: This analysis investigated whether a statistically significant change in AST levels was observed when comparing MRX baseline to Week 48. The analysis was based on the safety population.p-value: 0.157195% CI: [-9.1, 51.6]Student's t-test
Secondary
Change From MRX Baseline to Week 48 in Clinician Xanthoma Severity Score
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in clinician xanthoma severity scores. It is based on a 0-4 scale to rate the number of lesions present and the degree to which the participant's lesions interfere or limit his or her activities. Clinician xanthoma severity scores range from 0 to 4, with a xanthoma score of zero representing no evidence of xanthomatosis and a score of 4 representing xanthoma so severe that it is disabling. Clinician xanthoma severity scores were not assessed in Study LUM001-302 so mean clinician xanthoma severity score at MRX baseline was calculated from the 5 participants who were assigned to placebo in Study LUM001-302, and analysis of change from MRX baseline is not presented.
Time frame: MRX baseline to Week 48
Population: Mean MRX baseline scores were calculated from the 5 participants assigned placebo in LUM001-302 who had a baseline value in study LUM001-303. Those assigned to MRX within study LUM001-302 did not have this data collected at baseline.~Mean MRX Week 48 scores were calculated from 17 participants. Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline to Week 48 in Clinician Xanthoma Severity Score | 0.4 scores on a scale | Standard Deviation 0.55 |
| Core Study Period: Week 48 Values | Change From MRX Baseline to Week 48 in Clinician Xanthoma Severity Score | 0.2 scores on a scale | Standard Deviation 0.73 |
Secondary
Change From MRX Baseline to Week 48 in Gamma Glutamyltransferase
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in GGT.
Time frame: MRX baseline to Week 48
Population: Data collected from 19 participants at MRX baseline. Data collected at Week 48 from 17 of the 19 participants who contributed values at MRX baseline. Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline to Week 48 in Gamma Glutamyltransferase | 476.9 U/L | Standard Deviation 376.85 |
| Core Study Period: Week 48 Values | Change From MRX Baseline to Week 48 in Gamma Glutamyltransferase | 440.5 U/L | Standard Deviation 230.6 |
Comparison: This analysis investigated whether a statistically significant change in GGT levels was observed when comparing MRX baseline to Week 48. The analysis was based on the safety population.p-value: 0.951395% CI: [-136.4, 128.7]Student's t-test
Secondary
Change From MRX Baseline to Week 48 in Pruritus
This secondary efficacy endpoint is the change from MRX baseline to Week 48 in pruritus as measured by ItchRO(Obs) weekly average morning severity score. ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe).
Time frame: MRX baseline to Week 48
Population: Values were collected from 19 participants at MRX baseline. Data collected at Week 48 from 17 of the 19 participants who contributed values at MRX baseline.~Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline to Week 48 in Pruritus | 2.435 scores on a scale | Standard Deviation 0.7952 |
| Core Study Period: Week 48 Values | Change From MRX Baseline to Week 48 in Pruritus | 1.307 scores on a scale | Standard Deviation 0.6995 |
Comparison: This analysis investigated whether a statistically significant change in ItchRO(Obs) scores was observed when comparing MRX baseline to Week 48. The analysis was based on the safety population.p-value: <0.000195% CI: [-1.464, -0.726]Student's t-test
Secondary
Change From MRX Baseline to Week 48 in Total and Direct Bilirubin
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in total bilirubin and direct bilirubin.
Time frame: MRX baseline to Week 48
Population: Data collected from 19 participants at MRX baseline. Data collected at Week 48 from 17 of the 19 participants who contributed values at MRX baseline. Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core Study Period: MRX Baseline Values | Change From MRX Baseline to Week 48 in Total and Direct Bilirubin | Total bilirubin | 4.47 mg/dL | Standard Deviation 4.837 |
| Core Study Period: MRX Baseline Values | Change From MRX Baseline to Week 48 in Total and Direct Bilirubin | Direct bilirubin | 3.80 mg/dL | Standard Deviation 3.858 |
| Core Study Period: Week 48 Values | Change From MRX Baseline to Week 48 in Total and Direct Bilirubin | Total bilirubin | 4.25 mg/dL | Standard Deviation 5.384 |
| Core Study Period: Week 48 Values | Change From MRX Baseline to Week 48 in Total and Direct Bilirubin | Direct bilirubin | 3.21 mg/dL | Standard Deviation 3.656 |
Comparison: This analysis investigated whether a statistically significant change in total bilirubin levels was observed when comparing MRX baseline to Week 48. The analysis was based on the safety population.p-value: 0.783995% CI: [-1.05, 1.37]Student's t-test
Comparison: This analysis investigated whether a statistically significant change in direct bilirubin levels was observed when comparing MRX baseline to Week 48. The analysis was based on the safety population.p-value: 0.529895% CI: [-0.66, 0.35]Student's t-test
Secondary
Secondary: Change From MRX Baseline to Week 48 in Alkaline Phosphatase
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALP.
Time frame: MRX baseline to Week 48
Population: Data collected from 19 participants at MRX baseline. \[Data collected at Week 48 from 17 of the 19 participants who contributed values at MRX baseline. Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Study Period: MRX Baseline Values | Secondary: Change From MRX Baseline to Week 48 in Alkaline Phosphatase | 601.5 U/L | Standard Deviation 232.54 |
| Core Study Period: Week 48 Values | Secondary: Change From MRX Baseline to Week 48 in Alkaline Phosphatase | 596.2 U/L | Standard Deviation 185.2 |
Comparison: This analysis investigated whether a statistically significant change in ALP levels was observed when comparing MRX baseline to Week 48. The analysis was based on the safety population.p-value: 0.886395% CI: [-100.7, 115.6]Student's t-test