Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Lumasiran · 6 trials · 12 indications
Percent change in plasma oxalate (umol/L) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. For Cohort A, the baseline was defined as the mean of all plasma oxalate level values collected prior to the first dose of lumasiran.
Percent change in plasma oxalate (umol/L) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. For Cohort B, the baseline is defined as the mean of the last four pre-dialysis plasma oxalate samples collected prior to the first dose of lumasiran. In Cohort B, only pre-dialysis samples are utilized.
Percent change in spot urinary oxalate:creatinine ratio was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome.
Percent change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average percent change from baseline across Months 3 through 6. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome.
The primary endpoint is the percentage change in pre-dialysis plasma oxalate levels in non-primary hyperoxaluria patients with raised plasma oxalate levels who are receiving maintenance haemodialysis.
AE is any untoward medical occurrence in a participant or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Safety analysis set included all participants who received any amount of study drug.
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.
| Arm | Type | Description |
|---|---|---|
| Lumasiran | EXPERIMENTAL | All patients will receive open-label lumasiran. |
| Placebo/Lumasiran | PLACEBO_COMPARATOR | Lumasiran-matching placebo (normal saline \[0.9% NaCl\]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) period. |
| Lumasiran/Lumasiran | EXPERIMENTAL | Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period. |
| Lumasiran, treatment arm | EXPERIMENTAL | Treatment arm with Lumasiran |
| Placebo | PLACEBO_COMPARATOR | Placebo injection with 0.9% sodium chloride |
| Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M | EXPERIMENTAL | Participants enrolling from study 001B (NCT02706886), received lumasiran, subcutaneous (SC) injection, at a starting dose of 1.0 milligrams per kilograms (mg/kg) once monthly (QM) or 3.0 mg/kg once every 3 months \[Q3M\]) from Day 1 up to a maximum of Month 6. By Month 6, all participants were approved to change dose and/or dosing regimen to receive lumasiran, SC injection at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period. All 3 participants who began treatment at 1 mg/kg QM transitioned to 3 mg/kg Q3M regimen by Month 6. As the cumulative dose administered over 6 months was the same for both 1 mg/kg QM \& 3 mg/kg Q3M, these participants were pooled into one arm as recommended by the Safety Review Committee (SRC). |
| Lumasiran (ALN-GO1): 3.0 mg/kg QM | EXPERIMENTAL | Participants enrolling from study 001B, received lumasiran, SC injection, at a starting dose of 3.0 mg/kg, QM, from Day 1 up to a maximum of Month 21. By Month 21, all participants were approved to change dosing regimen to receive lumasiran, SC injection, at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period. |
| Part A: SAD: Placebo | PLACEBO_COMPARATOR | A single dose of matching placebo will be administered subcutaneously (SC). |
| Part A: SAD: Lumasiran 0.3 mg/kg | EXPERIMENTAL | A single dose of 0.3 mg/kg lumasiran will be administered SC. |
| Part A: SAD: Lumasiran 1.0 mg/kg | EXPERIMENTAL | A single dose of 1.0 mg/kg lumasiran will be administered SC. |
| Part A: SAD: Lumasiran 3.0 mg/kg | EXPERIMENTAL | A single dose of 3.0 mg/kg lumasiran will be administered SC. |
| Part A: SAD: Lumasiran 6.0 mg/kg | EXPERIMENTAL | A single dose of 6.0 mg/kg lumasiran will be administered SC. |
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| Lumasiran | DRUG | Lumasiran will be administered by subcutaneous (SC) injection. |
| Placebo | DRUG | Placebo by SC injection |
| 0.9% Sodium Chloride (placebo) | DRUG | Placebo, subcutaneous injection, given as three monthly loading doses followed by one further maintenance dose. |
Inclusion Criteria: * Has documented diagnosis of primary hyperoxaluria type 1 (PH1) * Estimated glomerular filtration rate (eGFR) ≤45 mL/min/1.73 m\^2 for patients ≥12 months of age (\<12 months of age, must have serum creatinine considered elevated for age) * Meets plasma oxalate level requiremen...
Lumasiran is an investigational small molecule being studied for Primary Hyperoxaluria Type 1 (PH1), a rare genetic condition, and for hyperoxalemia in patients on haemodialysis. It is being developed by Alnylam Pharmaceuticals for these indications.
Lumasiran is a small molecule with a -siran (siRNA) target class. It is designed to target the AGT gene, which is involved in the pathway leading to oxalate overproduction in Primary Hyperoxaluria Type 1.
Lumasiran is being developed by Alnylam Pharmaceuticals, Inc., a biopharmaceutical company traded on the stock exchange under the ticker symbol ALNY.
Lumasiran is in Phase 2 clinical development. It has completed Phase 2 and Phase 3 trials, and a Phase 2 trial in haemodialysis patients is currently recruiting participants.
Lumasiran has been studied in several clinical trials, including NCT03350451, NCT03905694, NCT04152200, and NCT06225544. The trials cover PH1 and hyperoxalemia in haemodialysis patients, with the latter currently recruiting.
Yes, Lumasiran is also known as ALN-GO1. This alternative name appears in the title of the extension study NCT03350451, which refers to Lumasiran as ALN-GO1.