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Safety and Tolerability of RTX-134 in Adults With Phenylketonuria

Primary Purpose

Phenylketonurias

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RTX-134
Sponsored by
Rubius Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Phenylketonurias

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital Colorado

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RTX-134

Arm Description

Escalating doses of RTX-134 will be administered by intravenous infusion one time

Outcomes

Primary Outcome Measures

To evaluate the safety and tolerability of RTX-134 as measured by frequency of treatment emergent adverse events
To correlate dose with percent reduction in serum phenylalanine levels relative to baseline
To determine a preliminary dose to achieve serum phenylalanine levels < 600 µmol/L
To determine a preliminary dose to achieve serum phenylalanine levels < 360 µmol/L
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.

Secondary Outcome Measures

Full Information

First Posted
September 23, 2019
Last Updated
December 7, 2022
Sponsor
Rubius Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT04110496
Brief Title
Safety and Tolerability of RTX-134 in Adults With Phenylketonuria
Official Title
A Phase 1b Open-Label Single Dose Safety, Tolerability, and Pharmacokinetics Study of RTX-134 in Adults With Phenylketonuria
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Terminated
Why Stopped
The trial was discontinued by the Sponsor
Study Start Date
January 29, 2020 (Actual)
Primary Completion Date
December 1, 2022 (Actual)
Study Completion Date
December 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rubius Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Phenylketonurias

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Single Ascending Dose
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RTX-134
Arm Type
Experimental
Arm Description
Escalating doses of RTX-134 will be administered by intravenous infusion one time
Intervention Type
Drug
Intervention Name(s)
RTX-134
Intervention Description
RTX-134 is a cellular therapy containing AvPAL
Primary Outcome Measure Information:
Title
To evaluate the safety and tolerability of RTX-134 as measured by frequency of treatment emergent adverse events
Time Frame
Baseline to 28 days after last detection of RTX-134
Title
To correlate dose with percent reduction in serum phenylalanine levels relative to baseline
Time Frame
Baseline to 28 days after last detection of RTX-134
Title
To determine a preliminary dose to achieve serum phenylalanine levels < 600 µmol/L
Time Frame
Baseline to 28 days after last detection of RTX-134
Title
To determine a preliminary dose to achieve serum phenylalanine levels < 360 µmol/L
Time Frame
Baseline to 28 days after last detection of RTX-134
Title
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.
Time Frame
Baseline to 28 days after last detection of RTX-134

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Safety and Tolerability of RTX-134 in Adults With Phenylketonuria

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