An Extension Study of an Investigational Drug, Lumasiran (ALN-GO1), in Participants With Primary Hyperoxaluria Type 1

Primary Hyperoxaluria Clinical Trial

Official title:

A Phase 2, Multicenter, Open-Label, Extension Study to Evaluate the Long-Term Administration of ALN-GO1 in Patients With Primary Hyperoxaluria Type 1

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03350451
• Other study ID #: ALN-GO1-002
• Secondary ID: 2016-003134-24
• Status: Completed
• Phase: Phase 2
• Start date: April 4, 2018
• Est. completion date: February 7, 2023

Study information

• Verified date: March 2024
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the long-term safety and tolerability of lumasiran in participants with Primary Hyperoxaluria Type 1.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 7, 2023
• Est. primary completion date: February 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

• Enrollment within 12 months of completion of Study ALN-GO1-001
• In the opinion of the investigator tolerated the study drug
• If taking Vitamin B6 (pyridoxine), willing to remain on a stable regimen for the study duration
• Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use a highly effective method of contraception
• Willing to provide written informed consent and to comply with study requirements

Exclusion Criteria:

• Clinically significant health concerns (with the exception of PH1)
• Clinically significant cardiovascular abnormality
• Abnormal for AST/ALT and any other clinical safety laboratory result considered clinically significant
• Requirement for chronic dialysis

Related Conditions & MeSH terms

• AGT
• Hyperoxaluria, Primary
• PH1
• Primary Hyperoxaluria
• RNAi Therapeutic
• siRNA

Intervention

Drug:
• Lumasiran
Multiple doses of lumasiran by SC injection

Locations

Country	Name	City	State
France	Clinical Trial Site	Bordeaux
France	Clinical Trial Site	Lyon
France	Clinical Trial Site	Paris
Germany	Clinical Trial Site	Bonn
Israel	Clinical Trial Site	Haifa
Israel	Clinical Trial Site	Jerusalem
Netherlands	Clinical Trial Site	Amsterdam
United Kingdom	Clinical Trial Site	Birmingham
United Kingdom	Clinical Trial Site	London

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

France,  Germany,  Israel,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With at Least One Adverse Event (AE)	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.	Baseline (Day -1) up to 54 months
Secondary	Change From Baseline in 24-hour Urinary Oxalate Corrected for Body Surface Area (BSA) at 54 Months	Oxalate produced by the liver is the key toxic metabolite that drives disease pathology in participants with primary hyperoxaluria type 1 (PH1). The risk of disease complications increase continuously as oxalate levels increase. 24-hour urinary oxalate (millimole [mmol]/ 24 hour [h]/1.73 meters squared [m^2]) corrected for BSA at each visit per participant was calculated as follows: [Urine oxalate concentration (micromole per liter [umol/L])/1000 (umol/mmol)]*[24hour urine volume (mL)/1000 (mL/L)]* [24 hours/actual collection hours]*1.73/(BSA). Baseline was the derived baseline value from the lumasiran treated period of Study ALN-GO1-001. A negative change from baseline indicated a favorable outcome. PD analysis set included all participants who received any amount of study drug and who had at least 1 post-dose urine sample for PD. Overall number of participants analyzed are the number of participants with data available for analysis.	Baseline (Day -1) up to 54 months
Secondary	Change From Baseline in 24-hour Urinary Oxalate:Creatinine Ratio at 54 Months	Baseline is the derived baseline value from the lumasiran treated period of Study ALN-GO1-001. A negative change from baseline indicates a favorable outcome. PD analysis set included all participants who received any amount of study drug and who had at least 1 post-dose urine sample for PD.	Baseline (Day -1) up to 54 months
Secondary	Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at 54 Months	Baseline was defined as the last measurement prior to the first dose of lumasiran in the ALN-GO1-001 study. eGFR was calculated based on the Modification of Diet in Renal Disease (MDRD) formula for participants >=18 years of age at enrollment and the Schwartz Bedside formula for participants <18 years of age at enrollment. eGFR based on MDRD formula was calculated as follows: eGFR (mL/min/1.73 m^2) = 175 × (serum creatinine {SCr} [µmol/deciliter(dL)]/88.4)-1.154 × (age)-0.203 × (0.742, if female), or × (1.212, if African American) and based on Schwartz formula: eGFR (mL/min/1.73m2) = (36.2 × height [cm])/ SCr (µmol /dL). Safety analysis set included all participants who received any amount of study drug.	Baseline (Day -1) up to 54 months