Safety and Tolerability of RTX-134 in Adults With Phenylketonuria

Study Overview
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Brief Summary
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This study will evaluate the safety and tolerability of RTX-134 in adult patients with PKU.

Detailed Description
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This is a Phase 1b first-in-human trial in adult subjects with PKU. The primary objective of this study is to evaluate the safety and tolerability of RTX-134 following intravenous administration of a single dose. RTX-134 consists of allogeneic human red cells expressing the AvPAL (Anabaena variabilis phenylalanine ammonia lyase) gene inside the cell. The trial is designed to determine a preliminary dose and inform a dosing schedule that is deemed safe, tolerable, and potentially effective. Four dose levels are planned, additional dose levels may be explored. Following administration, subjects will be monitored until 28 days after last detection of RTX-134. Detection of RTX-134 will be evaluated using multiple pharmacokinetic (PK) and pharmacodynamic (PD) assessments including measurement of trans-cinnamic acid (tCA).

Official Title
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A Phase 1b Open-Label Single Dose Safety, Tolerability, and Pharmacokinetics Study of RTX-134 in Adults With Phenylketonuria

Conditions
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Phenylketonurias

Intervention / Treatment
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* Drug: RTX-134


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age 18 years or older with: A clinical diagnosis of PKU, and Average blood phenylalanine level ≥ 600 µmol/L based on 2 assessments up to 3 weeks apart during the 6-month period before Day 0 (per available data) Stable diet, including medical formula Must be a man or a woman not of childbearing potential and agree to use adequate contraception throughout and for one year following study participation. Adequate organ function Negative antibody detection on type and screen and no evidence of clinical hemolysis Exclusion Criteria Known hypersensitivity to any component of study treatment Prior treatment with Pegaliase Start of sapropterin dihydrochloride within 3 weeks of study dosing Use of an investigational agent within 28 days of study dosing Concurrent participation in an interventional trial involving ongoing treatment, including placebo. Infections requiring antimicrobial treatment within 7 days of study dosing Chronic infections, such as HIV, hepatitis B, or untreated hepatitis C Conditions that may alter survival of red blood cells, (e.g., autoimmune diseases, splenectomy, etc) Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single Ascending Dose
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RTX-134<br>Escalating doses of RTX-134 will be administered by intravenous infusion one time | Drug: RTX-134<br>* RTX-134 is a cellular therapy containing AvPAL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of RTX-134 as measured by frequency of treatment emergent adverse events |  | Baseline to 28 days after last detection of RTX-134 | 
| To correlate dose with percent reduction in serum phenylalanine levels relative to baseline |  | Baseline to 28 days after last detection of RTX-134 | 
| To determine a preliminary dose to achieve serum phenylalanine levels < 600 µmol/L |  | Baseline to 28 days after last detection of RTX-134 | 
| To determine a preliminary dose to achieve serum phenylalanine levels < 360 µmol/L |  | Baseline to 28 days after last detection of RTX-134 | 
| To evaluate the pharmacokinetics of RTX-134 as measured by presence of AvPal expressing red cells, AvPAL protein in red cells and serum, and AvPAL enzymatic activity. |  | Baseline to 28 days after last detection of RTX-134 |