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The purpose of this study is to assess the safety, tolerability, and efficacy of ALN-PCSSC in participants with homozygous familial hypercholesterolemia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ALN-PCSSC | Experimental | 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ALN-PCSSC | Drug | ALN-PCSSC is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change From Day 1 to Day 90 in LDL-C | Due to the small number of subjects, and the fact that the data are not normally distributed, the data are presented as descriptive statistics with no inferential and limited summary statistics presented. | Day 1, Day 90 |
| Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C | Day 1, Day 180 (or Final Visit) |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in LDL-C | Day 1, Day 90, Day 180 (or Final Visit) | |
| Percentage Change From Day 1 to Day 60 and to Day 90 in PCSK9 | Day 1, Day 60, Day 90 |
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Inclusion Criteria:
Exclusion Criteria:
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
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| Name | Affiliation | Role |
|---|---|---|
| Kees Hovingh, MD, PhD | Department of Vascular Medicine, Academic Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site 201001 | Los Angeles | California | 90001 | United States | ||
| Research Site 231001 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Inclisiran | 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Inclisiran | 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Percentage Change From Day 1 to Day 90 in LDL-C | Due to the small number of subjects, and the fact that the data are not normally distributed, the data are presented as descriptive statistics with no inferential and limited summary statistics presented. | Posted | Mean | 95% Confidence Interval | percent change | Day 1, Day 90 |
|
18 months
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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 | Inclisiran | 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina unstable | Cardiac disorders | MedDRA 10.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina unstable | Cardiac disorders | MedDRA 10.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Frank Bosley, Vice-President, Regulatory Operaions | The Medicines Company | 9732906016 | frank.bosley@themedco.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 7, 2016 | Oct 23, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 14, 2018 | Oct 23, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000090542 | Homozygous Familial Hypercholesterolemia |
| ID | Term |
|---|---|
| D006938 | Hyperlipoproteinemia Type II |
| D008052 | Lipid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
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| ID | Term |
|---|---|
| C585830 | ALN-PCS |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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| Standard of Care | Drug | Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies. |
|
| Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9 | Day 1, Day 60, Day 90 |
| Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol | Day 1, Day 90, Day 180 (or Final Visit) |
| Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol | Day 1, Day 90, Day 180 (or Final Visit) |
| Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides | Day 1, Day 90, Day 180 (or Final Visit) |
| Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides | Day 1, Day 90, Day 180 (or Final Visit) |
| Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C | Day 1, Day 90, Day 180 (or Final Visit) |
| Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C | Day 1, Day 90, Day 180 (or Final Visit) |
| Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C | Day 1, Day 90, Day 180 (or Final Visit) |
| Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C | Day 1, Day 90, Day 180 (or Final Visit) |
| Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C | Day 1, Day 90, Day 180 (or Final Visit) |
| Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C | Day 1, Day 90, Day 180 (or Final Visit) |
| Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1 | Day 1, Day 90, Day 180 (or Final Visit) |
| Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1 | Day 1, Day 90, Day 180 (or Final Visit) |
| Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B | Day 1, Day 90, Day 180 (or Final Visit) |
| Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B | Day 1, Day 90, Day 180 (or Final Visit) |
| Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a | The reported percent change value is the per participant calculated Mean. | Day 1, Day 90, Day 180 (or Final Visit) |
| Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a | Day 1, Day 90, Day 180 (or Final Visit) |
| Amsterdam |
| Netherlands |
| Research Site 227001 | Parktown | Johannesburg | 2193 | South Africa |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Primary | Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C | Posted | Mean | 95% Confidence Interval | percent change | Day 1, Day 180 (or Final Visit) |
|
|
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| Secondary | Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in LDL-C | Posted | Mean | Standard Deviation | mg/dL | Day 1, Day 90, Day 180 (or Final Visit) |
|
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| Secondary | Percentage Change From Day 1 to Day 60 and to Day 90 in PCSK9 | Posted | Mean | Standard Deviation | percent change | Day 1, Day 60, Day 90 |
|
|
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| Secondary | Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9 | Posted | Mean | Standard Deviation | ng/mL | Day 1, Day 60, Day 90 |
|
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| Secondary | Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol | Posted | Mean | Standard Deviation | percent change | Day 1, Day 90, Day 180 (or Final Visit) |
|
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| Secondary | Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol | Posted | Mean | Standard Deviation | mg/dL | Day 1, Day 90, Day 180 (or Final Visit) |
|
|
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| Secondary | Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides | Posted | Mean | Standard Deviation | percent change | Day 1, Day 90, Day 180 (or Final Visit) |
|
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| Secondary | Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides | Posted | Mean | Standard Deviation | mg/dL | Day 1, Day 90, Day 180 (or Final Visit) |
|
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| Secondary | Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C | Posted | Mean | Standard Deviation | percent change | Day 1, Day 90, Day 180 (or Final Visit) |
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| Secondary | Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C | Posted | Mean | Standard Deviation | mg/dL | Day 1, Day 90, Day 180 (or Final Visit) |
|
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| Secondary | Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C | Posted | Mean | Standard Deviation | percent change | Day 1, Day 90, Day 180 (or Final Visit) |
|
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| Secondary | Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C | Posted | Mean | Standard Deviation | mg/dL | Day 1, Day 90, Day 180 (or Final Visit) |
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| Secondary | Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C | Posted | Mean | Standard Deviation | percent change | Day 1, Day 90, Day 180 (or Final Visit) |
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| Secondary | Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C | Posted | Mean | Standard Deviation | mg/dL | Day 1, Day 90, Day 180 (or Final Visit) |
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| Secondary | Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1 | Posted | Mean | Standard Deviation | percent change | Day 1, Day 90, Day 180 (or Final Visit) |
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| Secondary | Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1 | Posted | Mean | Standard Deviation | mg/dL | Day 1, Day 90, Day 180 (or Final Visit) |
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| Secondary | Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B | Posted | Mean | Standard Deviation | percent change | Day 1, Day 90, Day 180 (or Final Visit) |
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| Secondary | Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B | Posted | Mean | Standard Deviation | mg/dL | Day 1, Day 90, Day 180 (or Final Visit) |
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| Secondary | Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a | The reported percent change value is the per participant calculated Mean. | Posted | Mean | Standard Deviation | percent change | Day 1, Day 90, Day 180 (or Final Visit) |
|
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| Secondary | Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a | Posted | Mean | Standard Deviation | nmol/L | Day 1, Day 90, Day 180 (or Final Visit) |
|
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|
| 0 |
| 4 |
| 1 |
| 4 |
| 3 |
| 4 |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 10.0 | Non-systematic Assessment |
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| Non-cardiac chest pain | General disorders | MedDRA 10.0 | Non-systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Limb injury | Injury, poisoning and procedural complications | MedDRA 10.0 | Non-systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 10.0 | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Non-systematic Assessment |
|
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| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006951 | Hyperlipoproteinemias |
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |