Study of Lumasiran in Healthy Adults and Patients With Primary Hyperoxaluria Type 1
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ClinicalTrials.gov Identifier: NCT02706886 |
Recruitment Status :
Completed
First Posted : March 11, 2016
Results First Posted : January 30, 2020
Last Update Posted : January 30, 2020
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Primary Hyperoxaluria Type 1 (PH1) | Drug: Lumasiran Drug: Placebo | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 52 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Single (Participant) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1/2, Single-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Safety, Tolerability, Pharmacokinetic and Pharmacodynamics Study of Subcutaneously Administered ALN-GO1 in Healthy Adult Subjects, and Patients With Primary Hyperoxaluria Type 1 |
Actual Study Start Date : | March 8, 2016 |
Actual Primary Completion Date : | January 23, 2019 |
Actual Study Completion Date : | January 23, 2019 |

Arm | Intervention/treatment |
---|---|
Placebo Comparator: Part A: SAD: Placebo
A single dose of matching placebo will be administered subcutaneously (SC).
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Drug: Placebo
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). |
Experimental: Part A: SAD: Lumasiran 0.3 mg/kg
A single dose of 0.3 mg/kg lumasiran will be administered SC.
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Drug: Lumasiran
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).
Other Name: ALN-GO1 |
Experimental: Part A: SAD: Lumasiran 1.0 mg/kg
A single dose of 1.0 mg/kg lumasiran will be administered SC.
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Drug: Lumasiran
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).
Other Name: ALN-GO1 |
Experimental: Part A: SAD: Lumasiran 3.0 mg/kg
A single dose of 3.0 mg/kg lumasiran will be administered SC.
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Drug: Lumasiran
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).
Other Name: ALN-GO1 |
Experimental: Part A: SAD: Lumasiran 6.0 mg/kg
A single dose of 6.0 mg/kg lumasiran will be administered SC.
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Drug: Lumasiran
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).
Other Name: ALN-GO1 |
Placebo Comparator: Part B: MAD: Placebo
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.
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Drug: Placebo
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). |
Experimental: Part B: MAD: Lumasiran 1.0 mg/kg qM
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.
|
Drug: Lumasiran
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).
Other Name: ALN-GO1 |
Experimental: Part B: MAD: Lumasiran 3.0 mg/kg qM
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.
|
Drug: Lumasiran
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).
Other Name: ALN-GO1 |
Experimental: Part B: MAD: Lumasiran 3.0 mg/kg q3M
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.
|
Drug: Lumasiran
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).
Other Name: ALN-GO1 |
- Number of Participants With Adverse Events (AEs) [ Time Frame: Part A (SAD): Up to 405 days; Part B (MAD): Up to 546 days ]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.
- Maximum Concentration (Cmax) of Lumasiran in Plasma [ Time Frame: 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 ]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.
- Time to Cmax (Tmax) of Lumasiran in Plasma [ Time Frame: 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 ]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.
- Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Lumasiran in Plasma [ Time Frame: 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 ]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.
- Terminal Half-life (t1/2) of Lumasiran in Plasma [ Time Frame: 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 ]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.
- Fraction Excreted in Urine in 24 Hours (Fe0-24) of Lumasiran [ Time Frame: 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 ]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.
- Renal Clearance (CLR) of Lumasiran [ Time Frame: 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 ]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.
- Baseline Plasma Glycolate Concentration [ Time Frame: Part A (SAD): Baseline, Part B (MAD): Baseline ]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.
- Percentage Change From Baseline in Plasma Glycolate Concentration [ Time Frame: Part A (SAD): Days 15, 29, 57 and 85; Part B (MAD): Days 15, 29, 57, 85 ]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.
- Baseline Spot Urine Glycolate:Creatinine Ratio in Part A [ Time Frame: Part A (SAD): Baseline ]The endpoint was only measured in Part A.
- Percentage Change From Baseline in Spot Urine Glycolate:Creatinine Ratio in Part A [ Time Frame: Part A (SAD): Days 29 and 57 ]The endpoint was only measured in Part A.
- Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B [ Time Frame: Part B (MAD): Baseline ]The endpoint was only measured in Part B.
- Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B [ Time Frame: Part B (MAD): 24 hour urine collections on Days 29, 57, 85, 113, 141, 169, 197 ]The endpoint was only measured in Part B.
- Baseline 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days [ Time Frame: Part B (MAD): Baseline ]The endpoint was only measured during the initial 85 days in Part B.
- Percentage Change From Baseline of 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days [ Time Frame: Part B (MAD): 24 hour urine collections on Days 29, 57 and 85 ]The endpoint was only measured during the initial 85 days in Part B.
- Baseline Creatinine Clearance Corrected for BSA in Part B [ Time Frame: Part B (MAD): Baseline ]
- Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B [ Time Frame: Part B (MAD): Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449 ]

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Ages Eligible for Study: | 6 Years to 64 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria for Parts A and B:
- Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception.
- Willing to provide written informed consent and to comply with study requirements.
Additional Inclusion Criteria for Part B:
- Confirmation of PH1 disease
- Meet 24 hour urine oxalate excretion requirements
- Estimated glomerular filtration rate (GFR) of >45 mL/min/1.73m^2
- If taking Vitamin B6 (pyridoxine), must have been on stable regimen for at least 90 days
Exclusion Criteria for Parts A and B:
- Clinically significant health concerns (with the exception of PH1 for patients in Part B)
- Clinically significant electrocardiogram (ECG) abnormalities
- Abnormal for aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and any other clinical safety laboratory result considered clinically significant
- Received an investigational agent within 3 months before the first dose of study drug or are in follow-up of another clinical study
- Known history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc)
- History of intolerance to subcutaneous injection

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02706886
France | |
Clinical Trial Site | |
Bordeaux, France | |
Clinical Trial Site | |
Lyon, France | |
Clinical Trial Site | |
Paris, France | |
Germany | |
Clinical Trial Site | |
Bonn, Germany | |
Israel | |
Clinical Trial Site | |
Haifa, Israel | |
Clinical Trial Site | |
Jerusalem, Israel | |
Netherlands | |
Clinical Trial Site | |
Amsterdam, Netherlands | |
United Kingdom | |
Clinical Trial Site | |
Birmingham, United Kingdom | |
Clinical Trial Site | |
London, United Kingdom |
Study Director: | Tracy McGregor, MD, MSCI | Alnylam Pharmaceuticals |
Documents provided by Alnylam Pharmaceuticals:
Responsible Party: | Alnylam Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT02706886 |
Other Study ID Numbers: |
ALN-GO1-001 2015-004407-23 ( EudraCT Number ) |
First Posted: | March 11, 2016 Key Record Dates |
Results First Posted: | January 30, 2020 |
Last Update Posted: | January 30, 2020 |
Last Verified: | January 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
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