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: 1. Age 6 years or older. 2. Documentation or confirmation of PH1 as determined by genetic analysis prior to randomization. 3. Mean 24-hour urinary oxalate excretion from the first 2 valid 24-hour urine collections is =0.7 mmol/24h/1.73m2 4. If taking pyridoxine (vitamin B6) for the treatment of PH1, must have been on stable regimen for at least 90 days before randomization, and willing to remain on this stable regimen for 12 months from first study drug administration. 5. Patient is able to understand and is willing and able to comply with the study requirements and to provide written informed consent. In the case of patients under the age of legal consent, the legal guardian(s) must provide informed consent and the patient should provide assent per local and national requirements. Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Medical history includes clinical evidence of extrarenal systemic oxalosis, as determined by the Investigator. 2. Has any of the following laboratory parameter assessments at screening: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × upper limit of normal (ULN), total bilirubin >1.5 x ULN (patients with elevated total bilirubin that is secondary to documented Gilbert’s syndrome are eligible if the total bilirubin is 1.5 (patients on oral anticoagulant [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] 13. History of alcohol abuse, within the last 12 months before screening, in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of lumasiran on percent reduction in urinary oxalate excretion ;Secondary Objective: • To characterize the effect of lumasiran on absolute levels of urinary oxalate excretion and the oxalate:creatinine ratios, and plasma oxalate • To evaluate the effect of lumasiran, on renal function • To evaluate the long-term treatment effect of lumasiran ;Primary end point(s): Percent change in 24-hour urinary oxalate excretion from baseline to Month 6;Timepoint(s) of evaluation of this end point: 24-hour urine and blood samples will be collected for assessment of pharmacodynamic parameters each month. Urinary oxalate concentrations will be analyzed using a validated central assay at baseline and 6 months to assess the primary endpoint. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Absolute change in 24-hour urinary oxalate corrected for body surface area (BSA) from baseline to Month 6 • Change in 24-hour urinary oxalate:creatinine ratio (value/upper limit of normal [ULN]) from baseline to Month 6 • Proportion of patients with 24-hour urinary oxalate level at or below 1.5 x ULN at Month 6 • Proportion of patients with 24-hour urinary oxalate level at or below ULN at Month 6 • Change in estimated glomerular filtration rate (eGFR) from baseline to Month 6 • Percent change in plasma oxalate from baseline to Month 6 • Absolute change in plasma oxalate from baseline to Month 6 • Change from baseline (percent and absolute) in 24-hour urinary oxalate excretion, percentage of time that 24-hour urinary oxalate is = 1.5 × ULN, 24-hour urinary oxalate:creatinine ratios and eGFR in the extension periods ;Timepoint(s) of evaluation of this end point: 24-hour urine and blood samples will be collected for assessment of pharmacodynamic parameters each month. Urinary and plasma oxalate concentrations will be analyzed using a validated central assay at baseline and 6 months to assess the secondary endpoints. | — |
Countries
France, Germany, Israel, Jordan, Netherlands, Switzerland, United Arab Emirates, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Line
Alnylam Pharmaceuticals, Inc.
Outcome results
None listed