Study of Lumasiran in Healthy Adults and Patients With Primary Hyperoxaluria Type 1

Primary Hyperoxaluria Type 1 (PH1) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02706886
• Other study ID #: ALN-GO1-001
• Secondary ID: 2015-004407-23
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 8, 2016
• Est. completion date: January 23, 2019

Study information

• Verified date: January 2020
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: January 23, 2019
• Est. primary completion date: January 23, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperoxaluria, Primary
• Primary Hyperoxaluria Type 1 (PH1)

Intervention

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).
• 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).

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 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
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.	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
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.	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
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.	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
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.	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
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.	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	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
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.	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.	Part A (SAD): Days 15, 29, 57 and 85; Part B (MAD): Days 15, 29, 57, 85
Secondary	Baseline Spot Urine Glycolate:Creatinine Ratio in Part A	The endpoint was only measured in Part A.	Part A (SAD): Baseline
Secondary	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
Secondary	Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B	The endpoint was only measured in Part B.	Part B (MAD): Baseline
Secondary	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
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.	Part B (MAD): Baseline
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.	Part B (MAD): 24 hour urine collections on Days 29, 57 and 85
Secondary	Baseline Creatinine Clearance Corrected for BSA in Part B		Part B (MAD): Baseline
Secondary	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

External Links

•   For information about the drug ALN-GO1 and Primary Hyperoxaluria Type 1 (PH1), clink this link