About this trial
This study will be conducted to evaluate the efficacy and safety of YOLT-203 in children and adults with Primary Hyperoxaluria Type 1.
After the initial randomized, 6-month double-blind, placebo-controlled period, participants who were initially assigned to placebo will receive a single-dose of YOLT-203 treatment whereas participants in the YOLT-203 group will receive a single-dose of placebo infusion.
For patients interested in additional information on how to participate, please follow this link: https://mytomorro.ws/ph1trial.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
You are 6 years old or older.
You have been diagnosed with PH1 (primary hyperoxaluria type 1) through genetic testing.
Urine tests show that your oxalate levels are not within certain limits (based on at least two 24-hour urine collections).
If you take vitamin B6, your dose has been stable for at least 3 months, and you are willing to keep it the same during the study.
Disqualifiers
You have signs that oxalate has affected parts of your body outside the kidneys.
Your liver blood tests are not within certain limits.
You have certain abnormal blood clotting results (unless controlled with medication like warfarin).
You have HIV, or active or chronic hepatitis C.
Trial design
Crossover
Treatments tested in this trial
YOLT-203
GeneticYOLT-203 is an investigational gene editing therapy being evaluated for the treatment of Primary Hyperoxaluria Type 1 (PH1). It is administered by intravenous infusion over 1 hour.
Placebo
DrugPlacebo is a matching intravenous infusion administered over 1 hour.
Treatment groups
Trial outcomes
Primary outcomes
Percent Change From Baseline in 24-Hour Urinary Oxalate (BSA-Corrected)
Percent change from baseline in 24-hour urinary oxalate excretion corrected for body surface area (BSA) across Months 2 to 6.
Secondary outcomes
Change From Baseline in Plasma Oxalate
Percent and absolute change from baseline in plasma oxalate levels across Months 2 to 6.
Change in Estimated Glomerular Filtration Rate (eGFR)
Change from baseline in estimated glomerular filtration rate (eGFR).
Change in Kidney Stone Burden
Change from baseline in number and summed surface area of kidney stones as assessed by renal ultrasound.
Proportion of Participants Achieving Urinary Oxalate Thresholds
Proportion of participants achieving urinary oxalate levels ≤ upper limit of normal (ULN) and ≤ 1.5 × ULN at Month 6.
Other outcomes
Health-Related Quality of Life
Change from baseline in EQ-5D Health State Profile and Visual Analog Scale (VAS) scores.
Change in urinary and plasma glycolate
Change from baseline in urinary and plasma glycolate levels.
Change in urinary oxalate:creatinine ratio
Change from baseline in urinary oxalate:creatinine ratio from spot urine samples.
Anti-Drug Antibody Incidence
Incidence of anti-drug antibodies (ADAs) against polyethylene glycol (PEG) and CRISPR-associated protein 12 (Cas12).
Sponsors and contacts
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