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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-005346-38 | EudraCT Number | ||
| SHP625-302 | Other Identifier | Shire Development LLC |
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The study is a randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of LUM001. Efficacy will be assessed by evaluating the effect of LUM001 versus placebo on the biochemical markers and pruritus associated with Alagille Syndrome.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LUM001 | Experimental | LUM001 administered orally once each day |
|
| Placebo | Placebo Comparator | Placebo administered orally once each day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LUM001 | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 13 (End of Treatment) in Fasting Serum Bile Acid 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. | Baseline to 13 weeks or end of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 13 (End of Treatment) in Liver Enzymes | Analysis of liver enzymes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). A negative change from baseline indicates that the level of that enzyme decreased. | Baseline to 13 weeks or end of treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Mirum | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Birmingham Children's Hospital | Birmingham | West Midlands | B4 6NH | United Kingdom | ||
| Leeds Teaching Hospitals |
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| ID | Title | Description |
|---|---|---|
| FG000 | LUM001 140ug/kg/Day | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment. |
| FG001 | LUM001 280ug/kg/Day | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment. |
| FG002 | Placebo Cohort A | Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment. |
| FG003 | Placebo Cohort B | Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All randomized participants
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| ID | Title | Description |
|---|---|---|
| BG000 | LUM001 140ug/kg/Day | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline to Week 13 (End of Treatment) in Fasting Serum Bile Acid 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. | The modified Intent-to-Treat (mITT) population, defined as all participants in the Safety population who had at least 1 post-baseline efficacy assessment. The Safety population was defined as all participants who were randomly assigned to study treatment and who received any amount of study drug. | Posted | Least Squares Mean | Standard Error | umol/L | Baseline to 13 weeks or end of treatment |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LUM001 140ug/kg/Day | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bradycardia | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Physician | Mirum | +1 650-667-4085 | medinfo@mirumpharma.com |
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| ID | Term |
|---|---|
| D016738 | Alagille Syndrome |
| ID | Term |
|---|---|
| D002780 | Cholestasis, Intrahepatic |
| D002779 | Cholestasis |
| D001649 | Bile Duct Diseases |
| D001660 | Biliary Tract Diseases |
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|
| Change From Baseline to Week 13 (End of Treatment) in Pruritus as Measured by The Patient And Observer Itch Reported Outcome (ItchRO) Average Daily Scores |
The ItchRO was administered as a twice daily electronic diary (eDiary). Children ≥9 years of age completed the patient ItchRO; those between the ages of 5 and 8 completed the patient ItchRO with the assistance of their caregiver. There was no patient report for subjects under the age of 5. ItchRO scores range from 0 to 4, with the higher score indicating increasing itch severity. ItchRO average daily scores were calculated as the sum of daily scores (ie, the maximum of morning and evening scores) divided by the number of days. The average daily score was calculated by using the 7 days pre-treatment for baseline, and the last 7 days of treatment for Week 13. A negative change from Baseline indicates that itch severity decreased. |
| Baseline to 13 weeks or end of treatment |
| Leeds |
| West Yorkshire |
| LS9 7TF |
| United Kingdom |
| Kings College Hospital | London | SE5 9RS | United Kingdom |
| LUM001 280ug/kg/Day |
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment. |
| BG002 | Placebo Cohort A | Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment. |
| BG003 | Placebo Cohort B | Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Number | participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | LUM001 280ug/kg/Day | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment. |
| OG002 | LUM001 Overall | Participants received either dose of LUM001 for up to 10 or 13 weeks, then were followed for 4 weeks after treatment. |
| OG003 | Placebo Overall | Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment. |
|
|
|
| Secondary | Change From Baseline to Week 13 (End of Treatment) in Liver Enzymes | Analysis of liver enzymes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). A negative change from baseline indicates that the level of that enzyme decreased. | The mITT population, defined as all participants in the Safety population who had at least 1 post-baseline efficacy assessment. The Safety population was defined as all participants who were randomly assigned to study treatment and who received any amount of study drug. | Posted | Least Squares Mean | Standard Error | U/L | Baseline to 13 weeks or end of treatment |
|
|
|
|
| Secondary | Change From Baseline to Week 13 (End of Treatment) in Pruritus as Measured by The Patient And Observer Itch Reported Outcome (ItchRO) Average Daily Scores | The ItchRO was administered as a twice daily electronic diary (eDiary). Children ≥9 years of age completed the patient ItchRO; those between the ages of 5 and 8 completed the patient ItchRO with the assistance of their caregiver. There was no patient report for subjects under the age of 5. ItchRO scores range from 0 to 4, with the higher score indicating increasing itch severity. ItchRO average daily scores were calculated as the sum of daily scores (ie, the maximum of morning and evening scores) divided by the number of days. The average daily score was calculated by using the 7 days pre-treatment for baseline, and the last 7 days of treatment for Week 13. A negative change from Baseline indicates that itch severity decreased. | The mITT population, defined as all participants in the Safety population who had at least 1 post-baseline efficacy assessment. The Safety population was defined as all participants who were randomly assigned to study treatment and who received any amount of study drug. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline to 13 weeks or end of treatment |
|
|
|
|
| 0 |
| 6 |
| 6 |
| 6 |
| EG001 | LUM001 280ug/kg/Day | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment. | 0 | 8 | 7 | 8 |
| EG002 | Placebo Overall | Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment. | 0 | 6 | 4 | 6 |
| Deafness unilateral | Ear and labyrinth disorders | MedDRA (16.0) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (16.0) | Systematic Assessment |
|
| Middle ear inflammation | Ear and labyrinth disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Frequent bowel movements | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Crying | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Feeling abnormal | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Viral rash | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Anal injury | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Body temperature increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Vitamin E deficiency | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abnormal behaviour | Psychiatric disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually
| D004066 |
| Digestive System Diseases |
| D008107 | Liver Diseases |
| D006330 | Heart Defects, Congenital |
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| AST |
|
| ALP |
|
| 0.7827 |
| LS mean difference from placebo |
| 7.8 |
| 2-Sided |
| 95 |
| -51.4 |
| 67.0 |
| Superiority or Other |
| Analysis of all doses of LUM001 for ALT | ANCOVA | 0.2235 | LS mean difference from placebo | 32.2 | 2-Sided | 95 | -21.9 | 86.3 | Superiority or Other |
| Analysis of LUM001 140ug/kg/day for AST | ANCOVA | 0.2372 | LS mean difference from placebo | 24.0 | 2-Sided | 95 | -17.5 | 65.5 | Superiority or Other |
| Analysis of LUM001 280ug/kg/day for AST | ANCOVA | 0.3914 | LS mean difference from placebo | -15.8 | 2-Sided | 95 | -54.1 | 22.4 | Superiority or Other |
| Analysis of all doses of LUM001 for AST | ANCOVA | 0.8081 | LS mean difference from placebo | 4.1 | 2-Sided | 95 | -31.0 | 39.1 | Superiority or Other |
| Analysis of LUM001 140ug/kg/day for ALP | ANCOVA | 0.5748 | LS mean difference from placebo | 51.7 | 2-Sided | 95 | -140.3 | 243.7 | Superiority or Other |
| Analysis of LUM001 280ug/kg/day for ALP | ANCOVA | 0.8835 | LS mean difference from placebo | 11.9 | 2-Sided | 95 | -158.4 | 182.2 | Superiority or Other |
| Analysis of all doses of LUM001 for ALP | ANCOVA | 0.6917 | LS mean difference from placebo | 31.8 | 2-Sided | 95 | -135.8 | 199.4 | Superiority or Other |
| Observer ItchRO |
|
| ANCOVA |
| 0.7897 |
| LS mean difference from placebo |
| 0.202 |
| 2-Sided |
| 95 |
| -1.647 |
| 2.052 |
| Superiority or Other |
| Analysis of all doses of LUM001 for Patient ItchRO | ANCOVA | 0.9203 | LS mean difference from placebo | -0.073 | 2-Sided | 95 | -1.850 | 1.705 | Superiority or Other |
| Analysis of LUM001 140ug/kg/day for Observer ItchRO | ANCOVA | 0.5966 | LS mean difference from placebo | -0.210 | 2-Sided | 95 | -1.038 | 0.618 | Superiority or Other |
| Analysis of LUM001 280ug/kg/day for Observer ItchRO | ANCOVA | 0.6320 | LS mean difference from placebo | 0.173 | 2-Sided | 95 | -0.580 | 0.926 | Superiority or Other |
| Analysis of all doses of LUM001 for Observer ItchRO | ANCOVA | 0.9547 | LS mean difference from placebo | -0.019 | 2-Sided | 95 | -0.710 | 0.673 | Superiority or Other |