PH1, Primary Hyperoxaluria Type 1
Conditions
Keywords
ph1, primary hyperoxaluria Type 1, yoltech, yolt203, primary hyperoxaluria, recurrent kidney stones, rare kidney stones, YOLT-203, genetic kidney stones, gene editing, gene therapy, AGXT gene, CRISPR-Cas9, Alanine Glyoxylate Aminotransferase Gene
Brief summary
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.
Interventions
GENETICYOLT-203
YOLT-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.
DRUGPlacebo
Placebo is a matching intravenous infusion administered over 1 hour.
Sponsors
YolTech Therapeutics Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
After the initial 6-month double-blind period, participants will enter a 6-month treatment extension 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.
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * You (and/or your parent or legal guardian, if you are under 18) understand the study and agree to follow all study requirements, including signing a consent form.
Exclusion criteria
* 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. * You are pregnant, planning to become pregnant, or breastfeeding. * You are not willing to use birth control during the study and for 6 months after (if applicable). * You are unable to limit alcohol intake to no more than about 2 drinks per day. * You have had alcohol or drug abuse in the past year. * You are unable to follow standard treatments for PH1 (such as drinking plenty of fluids, taking prescribed medications like potassium citrate, or following dietary advice).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in 24-Hour Urinary Oxalate (BSA-Corrected) | Months 2 to 6 | Percent change from baseline in 24-hour urinary oxalate excretion corrected for body surface area (BSA) across Months 2 to 6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Oxalate | Months 2 to 6 | Percent and absolute change from baseline in plasma oxalate levels across Months 2 to 6. |
| Change in Estimated Glomerular Filtration Rate (eGFR) | Baseline to Month 6 | Change from baseline in estimated glomerular filtration rate (eGFR). |
| Change in Kidney Stone Burden | Baseline to Month 6 | Change from baseline in number and summed surface area of kidney stones as assessed by renal ultrasound. |
| Proportion of Participants Achieving Urinary Oxalate Thresholds | Month 6 | Proportion of participants achieving urinary oxalate levels ≤ upper limit of normal (ULN) and ≤ 1.5 × ULN at Month 6. |
| Incidence of Adverse Events | Day 1 to Month 12 | Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), graded using CTCAE v6.0. |
| Pharmacokinetic Parameters of YOLT-203 (Cmax) | Dosing through Month 1 | Cmax for YOLT-203 components (mRNA, CRISPR RNA, and lipid nanoparticles). |
| Pharmacokinetic Parameters of YOLT-203 (AUC0-inf) | Dosing through Month 1 | AUC0-inf for YOLT-203 components (mRNA, CRISPR RNA, and lipid nanoparticles). |
Countries
United States
Contacts
CONTACTKim Marie Grabbe, MS, MBA
CONTACTClaudia Rainolter
STUDY_DIRECTORLing Xiao, MD, PhD
YolTech Therapeutics
Outcome results
None listed