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Completed

NCT Number: NCT02706886

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

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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Key information

Conditions

Primary Hyperoxaluria Type 1 (PH1) Carbohydrate Metabolism, Inborn Errors Congenital, Hereditary, and Neonatal Diseases and Abnormalities Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Hyperoxaluria Hyperoxaluria, Primary Kidney Diseases Male Urogenital Diseases Metabolic Diseases Metabolism, Inborn Errors Nutritional and Metabolic Diseases Primary hyperoxaluria type 1 Urogenital Diseases Urologic Diseases

Age range

6 year–64 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Clinical Trial Site, Bordeaux, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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).

Other names: ALN-GO1

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).

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Baseline Spot Urine Glycolate:Creatinine Ratio in Part A

    Time frame: Part A (SAD): Baseline

    The endpoint was only measured in Part A.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Baseline Creatinine Clearance Corrected for BSA in Part B

    Time frame: Part B (MAD): Baseline

  16. 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

Sponsors and collaborators

Lead sponsor

Alnylam Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2019
Study completion
2019
First posted
Mar 11, 2016
Registry last updated
Jan 30, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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