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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-004407-23 | EudraCT Number |
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single-ascending doses (SAD) and multiple-ascending doses (MAD) of lumasiran in healthy adult volunteers and subjects with primary hyperoxaluria type 1 (PH1). In Part A, single ascending dose (SAD) part, healthy adults were dosed with lumasiran or placebo once. In Part B, multiple ascending doses (MAD) part, patients with primary hyperoxaluria type 1 (PH1) were dosed with lumasiran or placebo. All patients that initially received placebo received lumasiran after completing placebo dosing.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: SAD: Placebo | Placebo Comparator | A single dose of matching placebo will be administered subcutaneously (SC). |
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| Part A: SAD: Lumasiran 0.3 mg/kg | Experimental | A single dose of 0.3 mg/kg lumasiran will be administered SC. |
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| Part A: SAD: Lumasiran 1.0 mg/kg | Experimental | A single dose of 1.0 mg/kg lumasiran will be administered SC. |
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| Part A: SAD: Lumasiran 3.0 mg/kg | Experimental | A single dose of 3.0 mg/kg lumasiran will be administered SC. |
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| Part A: SAD: Lumasiran 6.0 mg/kg | Experimental | A single dose of 6.0 mg/kg lumasiran will be administered SC. |
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| Part B: MAD: Placebo | Placebo Comparator | Participants with primary hyperoxaluria type 1 (PH1) will be treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo treated participants will cross over to their respective Part B lumasiran arms in the Part B: MAD Study Day 85-End of Study Period and will then be treated with lumasiran. The estimated total time on study was up to 546 days. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lumasiran | Drug | Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85). |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | An AE is any untoward medical occurrence in a clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. | Part A (SAD): Up to 405 days; Part B (MAD): Up to 546 days |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Concentration (Cmax) of Lumasiran in Plasma | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. | Part A (SAD): Day 1: predose, 30 minutes (min), 1 hour (h), 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h |
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Inclusion Criteria for Parts A and B:
Additional Inclusion Criteria for Part B:
Exclusion Criteria for Parts A and B:
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| Name | Affiliation | Role |
|---|---|---|
| Tracy McGregor, MD, MSCI | Alnylam Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | Bordeaux | France | ||||
| Clinical Trial Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41388232 | Derived | Badri P, Kolachana K, Duong A, Lasko M, Nandi T, Mehrotra N, Robbie GJ. Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules. Clin Pharmacokinet. 2026 Feb;65(2):293-311. doi: 10.1007/s40262-025-01606-0. Epub 2025 Dec 12. | |
| 33985991 | Derived | Frishberg Y, Deschenes G, Groothoff JW, Hulton SA, Magen D, Harambat J, Van't Hoff WG, Lorch U, Milliner DS, Lieske JC, Haslett P, Garg PP, Vaishnaw AK, Talamudupula S, Lu J, Habtemariam BA, Erbe DV, McGregor TL, Cochat P; study collaborators. Phase 1/2 Study of Lumasiran for Treatment of Primary Hyperoxaluria Type 1: A Placebo-Controlled Randomized Clinical Trial. Clin J Am Soc Nephrol. 2021 Jul;16(7):1025-1036. doi: 10.2215/CJN.14730920. Epub 2021 May 13. |
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In Part A, single ascending dose (SAD) part, healthy adults were dosed with lumasiran or placebo once. In Part B, multiple ascending doses (MAD) part, patients with primary hyperoxaluria type 1 (PH1) were dosed with lumasiran or placebo. All patients, who initially received placebo, received lumasiran after completing placebo dosing.
Participants were enrolled at ten sites in Germany, France, the United Kingdom, Israel, and the Netherlands.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: SAD: Placebo | A single dose of matching placebo was administered subcutaneously (SC). |
| FG001 | Part A: SAD: Lumasiran 0.3 mg/kg | A single dose of 0.3 mg/kg lumasiran was administered SC. |
| FG002 | Part A: SAD: Lumasiran 1.0 mg/kg | A single dose of 1.0 mg/kg lumasiran was administered SC. |
| FG003 | Part A: SAD: Lumasiran 3.0 mg/kg | A single dose of 3.0 mg/kg lumasiran was administered SC. |
| FG004 | Part A: SAD: Lumasiran 6.0 mg/kg | A single dose of 6.0 mg/kg lumasiran was administered SC. |
| FG005 | Part B: MAD: Placebo | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days. |
| FG006 | Part B: MAD: Lumasiran 1.0 mg/kg qM | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| FG007 | Part B: MAD: Lumasiran 3.0 mg/kg qM | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| FG008 | Part B: MAD: Lumasiran 3.0 mg/kg q3M | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A: SAD Period |
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| Part B: MAD Study Days 1-85 |
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| Part B: MAD Study Day 85-End of Study |
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Safety Analysis Set consisted of all healthy participants and participants who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received during the first period that they entered the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A: SAD: Placebo | A single dose of matching placebo was administered SC. |
| BG001 | Part A: SAD: Lumasiran 0.3 mg/kg | A single dose of 0.3 mg/kg lumasiran was administered SC. |
| Units | Counts |
|---|---|
| Participants |
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| 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 | Number of Participants With Adverse Events (AEs) | An AE is any untoward medical occurrence in a clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. | Safety Analysis Set consisted of all healthy participants and patients, who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms. | Posted | Count of Participants | Participants | Part A (SAD): Up to 405 days; Part B (MAD): Up to 546 days |
|
Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days
Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
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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 | Part A: SAD: Placebo | A single dose of matching placebo was administered. | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Alnylam Pharmaceuticals Inc | 866-330-0326 | Clinicaltrials@alnylam.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 1, 2017 | Jan 22, 2020 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Feb 14, 2018 | Jan 22, 2020 | Prot_001.pdf |
| ID | Term |
|---|---|
| C536414 | Primary hyperoxaluria type 1 |
| D006960 | Hyperoxaluria, Primary |
| ID | Term |
|---|---|
| D006959 | Hyperoxaluria |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| C000716350 | lumasiran |
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| Part B: MAD: Lumasiran 1.0 mg/kg qM | Experimental | Participants with PH1 will be treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85. |
|
| Part B: MAD: Lumasiran 3.0 mg/kg qM | Experimental | Participants with PH1 will be treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85. |
|
| Part B: MAD: Lumasiran 3.0 mg/kg q3M | Experimental | Participants with PH1 will be treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85. |
|
|
| Placebo | Drug | Matching placebo (sterile saline: 0.9% sodium chloride [NaCl]) will be administered SC once in Part A. In Part B matching placebo will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85). |
|
| Time to Cmax (Tmax) of Lumasiran in Plasma | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. | Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h |
| Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Lumasiran in Plasma | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. | Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h |
| Terminal Half-life (t1/2) of Lumasiran in Plasma | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. | Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h |
| Fraction Excreted in Urine in 24 Hours (Fe0-24) of Lumasiran | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. | Part A (SAD): Day 1: pooled urine 0-4 h, 4-8 h and 8-24 h; Part B (MAD): Part B (MAD phase): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: pooled urine 0-4 h, 4-8 h, 8-12 h and 12-24 h |
| Renal Clearance (CLR) of Lumasiran | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. | Part A (SAD): Day 1: pooled urine 0-4 h, 4-8 h and 8-24 h; Part B (MAD): Part B (MAD phase): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: pooled urine 0-4 h, 4-8 h, 8-12 h and 12-24 h |
| Baseline Plasma Glycolate Concentration | The pharmacodynamic (PD) outcome measure of plasma glycolate concentration could only be calculated for Part A. Due to an issue with the plasma glycolate assay at the testing laboratory the data for Part B could not be calculated. | Part A (SAD): Baseline, Part B (MAD): Baseline |
| Percentage Change From Baseline in Plasma Glycolate Concentration | The PD outcome measure of plasma glycolate concentration could only be calculated for Part A. Due to an issue with the plasma glycolate assay at the testing laboratory the data for Part B could not be calculated. | Part A (SAD): Days 15, 29, 57 and 85; Part B (MAD): Days 15, 29, 57, 85 |
| Baseline Spot Urine Glycolate:Creatinine Ratio in Part A | The endpoint was only measured in Part A. | Part A (SAD): Baseline |
| Percentage Change From Baseline in Spot Urine Glycolate:Creatinine Ratio in Part A | The endpoint was only measured in Part A. | Part A (SAD): Days 29 and 57 |
| Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B | The endpoint was only measured in Part B. | Part B (MAD): Baseline |
| Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B | The endpoint was only measured in Part B. | Part B (MAD): 24 hour urine collections on Days 29, 57, 85, 113, 141, 169, 197 |
| Baseline 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days | The endpoint was only measured during the initial 85 days in Part B. | Part B (MAD): Baseline |
| Percentage Change From Baseline of 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days | The endpoint was only measured during the initial 85 days in Part B. | Part B (MAD): 24 hour urine collections on Days 29, 57 and 85 |
| Baseline Creatinine Clearance Corrected for BSA in Part B | Part B (MAD): Baseline |
| Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B | Part B (MAD): Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449 |
| Lyon |
| France |
| Clinical Trial Site | Paris | France |
| Clinical Trial Site | Bonn | Germany |
| Clinical Trial Site | Haifa | Israel |
| Clinical Trial Site | Jerusalem | Israel |
| Clinical Trial Site | Amsterdam | Netherlands |
| Clinical Trial Site | Birmingham | United Kingdom |
| Clinical Trial Site | London | United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
|
| BG002 | Part A: SAD: Lumasiran 1.0 mg/kg | A single dose of 1.0 mg/kg lumasiran was administered SC. |
| BG003 | Part A: SAD: Lumasiran 3.0 mg/kg | A single dose of 3.0 mg/kg lumasiran was administered SC. |
| BG004 | Part A: SAD: Lumasiran 6.0 mg/kg | A single dose of 6.0 mg/kg lumasiran was administered SC. |
| BG005 | Part B: MAD: Placebo | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days. |
| BG006 | Part B: MAD: Lumasiran 1.0 mg/kg qM | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| BG007 | Part B: MAD: Lumasiran 3.0 mg/kg qM | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| BG008 | Part B: MAD: Lumasiran 3.0 mg/kg q3M | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| BG009 | Total | Total of all reporting groups |
| years |
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| 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 |
|
| Part A: SAD: Lumasiran 0.3 mg/kg |
A single dose of 0.3 mg/kg Lumasiran was administered SC. |
| OG002 | Part A: SAD: Lumasiran 1.0 mg/kg | A single dose of 1.0 mg/kg Lumasiran was administered SC. |
| OG003 | Part A: SAD: Lumasiran 3.0 mg/kg | A single dose of 3.0 mg/kg Lumasiran was administered SC. |
| OG004 | Part A: SAD: Lumasiran 6.0 mg/kg | A single dose of 6.0 mg/kg Lumasiran was administered SC. |
| OG005 | Part B: MAD: Placebo | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days. |
| OG006 | Part B: MAD: Lumasiran 1.0 mg/kg qM | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| OG007 | Part B: MAD: Lumasiran 3.0 mg/kg qM | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| OG008 | Part B: MAD: Lumasiran 3.0 mg/kg q3M | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
|
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| Secondary | Maximum Concentration (Cmax) of Lumasiran in Plasma | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. | Pharmacokinetic (PK) Analysis Set consisted of all healthy participants and patients who received at least 1 dose of lumasiran and had at least 1 postdose sample for PK parameters and who had evaluable PK data. | Posted | Mean | Standard Deviation | ng/mL | Part A (SAD): Day 1: predose, 30 minutes (min), 1 hour (h), 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h |
|
|
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| Secondary | Time to Cmax (Tmax) of Lumasiran in Plasma | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. | PK Analysis Set consisted of all healthy participants and patients who received at least 1 dose of lumasiran and had at least 1 postdose sample for PK parameters and who had evaluable PK data. | Posted | Median | Full Range | hours | Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h |
|
|
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| Secondary | Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Lumasiran in Plasma | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. | PK Analysis Set consisted of all healthy participants and patients who received at least 1 dose of lumasiran and had at least 1 postdose sample for PK parameters and who had evaluable PK data. | Posted | Mean | Standard Deviation | h*ng/mL | Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h |
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|
|
| Secondary | Terminal Half-life (t1/2) of Lumasiran in Plasma | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. | PK Analysis Set consisted of all healthy participants and patients who received at least 1 dose of lumasiran and had at least 1 postdose sample for PK parameters and who had evaluable PK data. | Posted | Mean | Standard Deviation | hours | Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h |
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| Secondary | Fraction Excreted in Urine in 24 Hours (Fe0-24) of Lumasiran | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. | PK Analysis Set consisted of all healthy participants and patients who received at least 1 dose of lumasiran and had at least 1 postdose sample for PK parameters and who had evaluable PK data. | Posted | Mean | Standard Deviation | percentage fractional excretion | Part A (SAD): Day 1: pooled urine 0-4 h, 4-8 h and 8-24 h; Part B (MAD): Part B (MAD phase): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: pooled urine 0-4 h, 4-8 h, 8-12 h and 12-24 h |
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|
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| Secondary | Renal Clearance (CLR) of Lumasiran | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. | PK Analysis Set consisted of all healthy participants and patients who received at least 1 dose of lumasiran and had at least 1 postdose sample for PK parameters and who had evaluable PK data. | Posted | Mean | Standard Deviation | L/h | Part A (SAD): Day 1: pooled urine 0-4 h, 4-8 h and 8-24 h; Part B (MAD): Part B (MAD phase): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: pooled urine 0-4 h, 4-8 h, 8-12 h and 12-24 h |
|
|
|
| Secondary | Baseline Plasma Glycolate Concentration | The pharmacodynamic (PD) outcome measure of plasma glycolate concentration could only be calculated for Part A. Due to an issue with the plasma glycolate assay at the testing laboratory the data for Part B could not be calculated. | PD Analysis Set consisted of all participants who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood sample available that was evaluable for PD assessments. Due to an issue with plasma glycolate assay at the testing laboratory the data for Part B could not be calculated. | Posted | Mean | Standard Deviation | umol/L | Part A (SAD): Baseline, Part B (MAD): Baseline |
|
|
|
| Secondary | Percentage Change From Baseline in Plasma Glycolate Concentration | The PD outcome measure of plasma glycolate concentration could only be calculated for Part A. Due to an issue with the plasma glycolate assay at the testing laboratory the data for Part B could not be calculated. | PD Analysis Set consisted of all participants who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood sample available that was evaluable for PD assessments. Due to an issue with plasma glycolate assay at the testing laboratory the data for Part B could not be calculated. | Posted | Mean | Standard Deviation | percentage change from baseline | Part A (SAD): Days 15, 29, 57 and 85; Part B (MAD): Days 15, 29, 57, 85 |
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| Secondary | Baseline Spot Urine Glycolate:Creatinine Ratio in Part A | The endpoint was only measured in Part A. | PD Analysis Set for Part A consisted of all healthy participants who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. | Posted | Mean | Standard Deviation | mg/g | Part A (SAD): Baseline |
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| Secondary | Percentage Change From Baseline in Spot Urine Glycolate:Creatinine Ratio in Part A | The endpoint was only measured in Part A. | PD Analysis Set in Part A consisted of all healthy participants who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. | Posted | Mean | Standard Deviation | percentage change from baseline | Part A (SAD): Days 29 and 57 |
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| Secondary | Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B | The endpoint was only measured in Part B. | PD Analysis Set in Part B consisted of all patients with PH1 who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. | Posted | Mean | Standard Deviation | mmol/24h/1.73m^2 | Part B (MAD): Baseline |
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| Secondary | Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B | The endpoint was only measured in Part B. | PD Analysis Set in Part B consisted of all patients with PH1 who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. | Posted | Mean | Standard Deviation | percentage change from baseline | Part B (MAD): 24 hour urine collections on Days 29, 57, 85, 113, 141, 169, 197 |
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| Secondary | Baseline 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days | The endpoint was only measured during the initial 85 days in Part B. | PD Analysis Set in Part B consisted of all patients with PH1 who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. | Posted | Mean | Standard Deviation | mg/g | Part B (MAD): Baseline |
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| Secondary | Percentage Change From Baseline of 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days | The endpoint was only measured during the initial 85 days in Part B. | PD Analysis Set in Part B consisted of all patients with PH1 who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. | Posted | Mean | Standard Deviation | percentage change from baseline | Part B (MAD): 24 hour urine collections on Days 29, 57 and 85 |
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| Secondary | Baseline Creatinine Clearance Corrected for BSA in Part B | PD Analysis Set in Part B consisted of all patients with PH1 who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. | Posted | Mean | Standard Deviation | mL/min/1.73 m^2 | Part B (MAD): Baseline |
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| Secondary | Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B | PD Analysis Set in Part B consisted of all patients with PH1 who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. | Posted | Mean | Standard Deviation | percentage change from baseline | Part B (MAD): Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449 |
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|
|
| 8 |
| 0 |
| 8 |
| 5 |
| 8 |
| EG001 | Part A: SAD: Lumasiran 0.3 mg/kg | A single dose of 0.3 mg/kg lumasiran was administered subcutaneously (SC). | 0 | 6 | 0 | 6 | 6 | 6 |
| EG002 | Part A: SAD: Lumasiran 1.0 mg/kg | A single dose of 1.0 mg/kg lumasiran was administered SC. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG003 | Part A: SAD: Lumasiran 3.0 mg/kg | A single dose of 3.0 mg/kg lumasiran was administered SC. | 0 | 6 | 0 | 6 | 6 | 6 |
| EG004 | Part A: SAD: Lumasiran 6.0 mg/kg | A single dose of 6.0 mg/kg lumasiran was administered SC. | 0 | 6 | 0 | 6 | 6 | 6 |
| EG005 | Part B: MAD: Placebo | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in the All-Lumasiran-Treated Period. The estimated total time on study was up to 546 days. | 0 | 3 | 1 | 3 | 2 | 3 |
| EG006 | Part B: MAD: Lumasiran 1.0 mg/kg qM | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. | 0 | 8 | 1 | 8 | 7 | 8 |
| EG007 | Part B: MAD: Lumasiran 3.0 mg/kg qM | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. | 0 | 8 | 3 | 8 | 7 | 8 |
| EG008 | Part B: MAD: Lumasiran 3.0 mg/kg q3M | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. | 0 | 4 | 0 | 4 | 4 | 4 |
| Nephrolithiasis | Renal and urinary disorders | MedDRA (18.1) | Systematic Assessment |
|
| Pyelonephritis acute | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (18.1) | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Faeces soft | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (18.1) | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA (18.1) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Periodontitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Viral pharyngitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
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| Head injury | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
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| Tendon injury | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA (18.1) | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA (18.1) | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA (18.1) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
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| Alcoholic hangover | Psychiatric disorders | MedDRA (18.1) | Systematic Assessment |
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| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Papule | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Rash follicular | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Skin texture abnormal | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Caffeine consumption | Social circumstances | MedDRA (18.1) | Systematic Assessment |
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| Lymph node pain | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
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| Visual impairment | Eye disorders | MedDRA (18.1) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Injection site bruising | General disorders | MedDRA (18.1) | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA (18.1) | Systematic Assessment |
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| Injection site pruritus | General disorders | MedDRA (18.1) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (18.1) | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Urinary tract infection enterococcal | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA (18.1) | Systematic Assessment |
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| Nephrolithiasis | Renal and urinary disorders | MedDRA (18.1) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Atrial septal defect | Congenital, familial and genetic disorders | MedDRA (18.1) | Systematic Assessment |
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| Dry eye | Eye disorders | MedDRA (18.1) | Systematic Assessment |
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| Eye swelling | Eye disorders | MedDRA (18.1) | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Teething | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Axillary pain | General disorders | MedDRA (18.1) | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA (18.1) | Systematic Assessment |
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| Injection site discolouration | General disorders | MedDRA (18.1) | Systematic Assessment |
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| Injection site swelling | General disorders | MedDRA (18.1) | Systematic Assessment |
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| Body tinea | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
|
| Dermatitis infected | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
|
| Urinary tract infection bacterial | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
|
| Urinary tract infection staphylococcal | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
|
| Soft tissue injury | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
|
| Blood phosphorus decreased | Investigations | MedDRA (18.1) | Systematic Assessment |
|
| Gout | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
|
| Increased appetite | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
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| Overweight | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
|
| Blister | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
|
| Tricuspid valve incompetence | Cardiac disorders | MedDRA (18.1) | Systematic Assessment |
|
Not provided
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| Day 57 |
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| Day 85 |
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| Day 57 |
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| Day 85 |
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| Day 57 |
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| Day 85 |
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| Day 57 |
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| Day 85 |
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| Day 57 |
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| Day 85 |
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| Day 57 |
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| Day 85 |
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| Day 29 |
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| Day 57 |
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| Day 85 |
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| Day 57 |
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| Day 57 |
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| Day 85 |
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| Day 113 |
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| Day 141 |
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| Day 169 |
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| Day 197 |
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| Day 57 |
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| Day 85 |
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| Day 57 |
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| Day 85 |
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| Day 113 |
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| Day 141 |
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| Day 169 |
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| Day 197 |
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| Day 225 |
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| Day 253 |
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| Day 281 |
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| Day 309 |
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| Day 337 |
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| Day 365 |
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| Day 393 |
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| Day 421 |
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| Day 449 |
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