Safety and Tolerability of RTX-134 in Adults With Phenylketonuria

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

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

Study Overview

• Status: Terminated
• Conditions: Phenylketonurias
• Intervention / Treatment: Drug: RTX-134

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Age 18 years or older with:

   1. A clinical diagnosis of PKU, and
   2. 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)
2. Stable diet, including medical formula
3. 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.
4. Adequate organ function
5. Negative antibody detection on type and screen and no evidence of clinical hemolysis

Exclusion Criteria

1. Known hypersensitivity to any component of study treatment
2. Prior treatment with Pegaliase
3. Start of sapropterin dihydrochloride within 3 weeks of study dosing
4. Use of an investigational agent within 28 days of study dosing
5. Concurrent participation in an interventional trial involving ongoing treatment, including placebo.
6. Infections requiring antimicrobial treatment within 7 days of study dosing
7. Chronic infections, such as HIV, hepatitis B, or untreated hepatitis C
8. Conditions that may alter survival of red blood cells, (e.g., autoimmune diseases, splenectomy, etc)
9. Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Rubius Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2020
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: September 23, 2019
• First Submitted That Met QC Criteria: September 27, 2019
• First Posted (Actual): October 1, 2019

Study Record Updates

• Last Update Posted (Estimate): December 8, 2022
• Last Update Submitted That Met QC Criteria: December 7, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Phenylketonurias
• Other Study ID Numbers: RTX-134-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No