Primary Hyperoxaluria Type 1 (PH1) MedDRA version: 20.1 Level: PT Classification code 10020703 Term: Hyperoxaluria System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Sponsors
Alnylam Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cohorts A and B 1. Have reached at least 37 weeks estimated gestational age (full-term infant) at consent (or assent). 2. Documentation or confirmation of PH1 as determined by genetic analysis prior to initial dosing. 3. Patients with eGFR =45 mL/min/1.73 m2 as calculated by the MDRD formula if =18 years or Schwartz Bedside Formula if =12 months to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Has any of the following laboratory parameter assessments at Screening: a. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2× ULN for age b. Total bilirubin >1.5×ULN. Patients with elevated total bilirubin that is secondary to documented Gilbert's syndrome are eligible if the total bilirubin is 1.5 for patients not on anticoagulants. Patients on oral anticoagulants (eg, warfarin) with an INR 2 units/day is excluded during the study (unit: 1 glass of wine [approximately 125 mL] = 1 measure of spirits [approximately 1 fluid ounce] = ½ pint of beer [approximately 284 mL]. 8. History of alcohol abuse, within the last 12 months before screening, in the opinion of the investigator. 9. Patients with a previous liver transplant or for whom a liver transplant is anticipated in the next 6 months. 10. Patients with a previous kidney transplant who are currently receiving immunosuppression to prevent transplant rejection. 11. Patients maintained on a peritoneal dialysis regimen. 12. Patients who in the opinion of the Investigator plan to start dialysis replacement therapy in the next 6 months. 13. Any comorbidity or condition that, in the opinion of the Investigator, is anticipated to prevent participation in at least 12 months of the study 14. Is not willing to comply with the contraceptive requirements during the study period, as described in study protocol. 15. Female patient is pregnant, planning a pregnancy, or breast feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Cohort A • Evaluate the effect of lumasiran on plasma oxalate in patients who are not on dialysis therapy Cohort B • Evaluate the effect of lumasiran on plasma oxalate levels in patients who are on dialysis therapy;Secondary Objective: • Evaluate the effect of lumasiran on change in plasma oxalate area under the curve (AUC) between dialysis sessions • Evaluate the long-term effects of lumasiran on change in plasma oxalate • Evaluate the effect of lumasiran on change in urinary oxalate excretion • Evaluate quality of life in patients with PH1 • Characterize the PK of lumasiran • Evaluate the effect of lumasiran on nephrocalcinosis • Evaluate the effect of lumasiran on dialysis requirements • Evaluate the effect of lumasiran on the occurrence of renal stones • Evaluate the effect of lumasiran on renal function • Evaluate the effect of lumasiran on change in measures of systemic oxalosis;Primary end point(s): Cohort A • Percent change in plasma oxalate from Baseline to Month 6 Cohort B • Percent change in pre-dialysis plasma oxalate from Baseline to Month 6;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Primary Analysis Period (Baseline to 6 months) • Percent change in plasma oxalate AUC between dialysis sessions • Absolute change in plasma oxalate • Change in the following parameters: *Urinary oxalate *QoL assessed by the PedsQL Total Score for patients =2 to <18 years of age at consent, and as assessed by KDQOL Burden of Kidney Disease and Effect of Kidney Disease on Daily Life subscales, and SF-12 Physical Component Summary and Mental Component Summary, in patients =18 years at consent • Plasma PK parameters of lumasiran Long-term Extension Period (6 months to end of study) • Percent change in plasma oxalate AUC between dialysis sessions • Percent and absolute change in plasma oxalate • Change in the following parameters: *Nephrocalcinosis as assessed by renal ultrasound *Frequency and mode of dialysis *Frequency of renal stone events *Urinary oxalate *Renal function as assessed by eGFR *Measures of systemic oxalosis in the following systems: -Cardiac -Dermatologic -Skeletal -Ocular *QoL(Quality of life) assessed by the PedsQL Total Score for patients =2 to <18 years of age at consent, and as assessed by KDQOL Burden of Kidney Disease and Effect of Kidney Disease on Daily Life subscales, and SF-12 Physical Component Summary and Mental Component Summary, in patients =18 years at consent;Timepoint(s) of evaluation of this end point: Primary Analysis Period: 6 months Long-term Extension Period: 6 months to 5 years | — |
Countries
Australia, Belgium, Egypt, France, Germany, India, Israel, Italy, Lebanon, Netherlands, Switzerland, Turkey, United Arab Emirates, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Line
Alnylam Pharmaceuticals, Inc.
Outcome results
None listed