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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| YOLT-203 | Experimental | Participants will receive both study treatments in sequential treatment periods according to randomized assignment. Participants who initially receive YOLT-203 during the double-blind treatment period and will cross over to the placebo treatment in the subsequent treatment period, followed by safety and efficacy follow-up. |
|
| Placebo | Placebo Comparator | Participants will receive both study treatments in sequential treatment periods according to randomized assignment. Participants who initially receive placebo during the double-blind treatment period and will cross over to the YOLT-203 treatment in the subsequent treatment period, followed by safety and efficacy follow-up. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| YOLT-203 | Genetic | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Months 2 to 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Plasma Oxalate | Percent and absolute change from baseline in plasma oxalate levels across Months 2 to 6. | Months 2 to 6 |
| Change in Estimated Glomerular Filtration Rate (eGFR) |
| Measure | Description | Time Frame |
|---|---|---|
| Health-Related Quality of Life | Change from baseline in EQ-5D Health State Profile and Visual Analog Scale (VAS) scores. | Baseline through Month 12 |
| Change in urinary and plasma glycolate | Change from baseline in urinary and plasma glycolate levels. |
Inclusion Criteria
Exclusion Criteria
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kim Marie Grabbe, MS, MBA | Contact | 217-851-5818 | Kim.Marie.Grabbe@yoltx.com | |
| Claudia Rainolter | Contact | 412-227-1722 | claudia.rainolter@yoltx.com |
| Name | Affiliation | Role |
|---|---|---|
| Ling Xiao, MD, PhD | YolTech Therapeutics | Study Director |
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| ID | Term |
|---|---|
| C536414 | Primary hyperoxaluria type 1 |
| D006959 | Hyperoxaluria |
| D006960 | Hyperoxaluria, Primary |
| D007669 | Kidney Calculi |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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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.
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| Placebo | Drug | Placebo is a matching intravenous infusion administered over 1 hour. |
|
Change from baseline in estimated glomerular filtration rate (eGFR).
| Baseline to Month 6 |
| Change in Kidney Stone Burden | Change from baseline in number and summed surface area of kidney stones as assessed by renal ultrasound. | Baseline to Month 6 |
| 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. | Month 6 |
| Incidence of Adverse Events | Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), graded using CTCAE v6.0. | Day 1 to Month 12 |
| Pharmacokinetic Parameters of YOLT-203 (Cmax) | Cmax for YOLT-203 components (mRNA, CRISPR RNA, and lipid nanoparticles). | Dosing through Month 1 |
| Pharmacokinetic Parameters of YOLT-203 (AUC0-inf) | AUC0-inf for YOLT-203 components (mRNA, CRISPR RNA, and lipid nanoparticles). | Dosing through Month 1 |
| Baseline to Month 6 |
| Change in urinary oxalate:creatinine ratio | Change from baseline in urinary oxalate:creatinine ratio from spot urine samples. | Baseline to Month 6 |
| Anti-Drug Antibody Incidence | Incidence of anti-drug antibodies (ADAs) against polyethylene glycol (PEG) and CRISPR-associated protein 12 (Cas12). | Baseline to Month 6 |
| Kidney stone events | Number of kidney stone events occurring during the study period. | Baseline to Month 6 |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D053040 | Nephrolithiasis |
| D052878 | Urolithiasis |
| D014545 | Urinary Calculi |
| D002137 | Calculi |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |