A Dose-finding Study to Evaluate mRNA-3210 in Participants With Phenylketonuria

A Phase 1/2, First-in-Human, Open-Label, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of mRNA 3210 in Participants With Phenylketonuria

The main goal of this study is to assess the safety, and tolerability of multiple doses of mRNA-3210 in participants with phenylketonuria (PKU).

Study Overview

• Status: Withdrawn
• Conditions: Phenylketonuria
• Intervention / Treatment: Drug: mRNA-3210

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5006
      • Royal Adelaide Hospital
• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed diagnosis of PKU due to phenylalanine hydroxylase (PAH) deficiency by molecular genetic testing from a central lab.
• At least 3 blood phenylalanine levels ≥600 micromole(μmol)/Litre (L) regardless of diet: 2 obtained during the screening period (at least 72 hours apart) and at least one historical value 6 to 24 months prior to start of screening.
• Have received documented approval from a study dietitian confirming that participant is willing and able to maintain dietary protein intake consistent with baseline intake during study participation.
• If applicable, maintained stable dose of neuropsychiatric medication (that is, for attention deficit hyperactivity disorder (ADHD), depression, anxiety, or other psychiatric disorders) prior to enrollment and willing to maintain stable dose throughout study participation unless, per investigator assessment, a change is clinically indicated.

Exclusion Criteria:

• Receipt of sapropterin or large-neutral amino acids within 14 days or 5 half-lives (whichever is longer) of the start of screening.
• Receipt of pegvaliase within 2 months of start of screening.
• For participants previously on pegvaliase: use or planned use of any injectable drugs containing polyethylene glycol (PEG), including medroxyprogesterone injection, within 3 months prior to the start of screening and during study participation with the exception of COVID-19 vaccinations.
• Receipt of any investigational drug within 30 days or 5-half-lives (whichever is longer) of screening.
• History of hypersensitivity to any component/excipient used in this study.
• Any other clinically significant medical condition that, in the Investigator's opinion, could interfere with the interpretation of study results or limit the participant's participation in the study

Note: Other protocol-defined inclusion/exclusion criteria apply.

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: mRNA-3210; Participants will receive single dose of mRNA-3210 by intravenous (IV) infusion every 3 weeks (Q3W), every 2 weeks (Q2W), or every 1 week (Q1W) for up to 12 doses.	Drug: mRNA-3210; IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Treatment Emergent Adverse Events (TEAEs)	Day 1 up to 52 weeks after EOT (up to 91 weeks)

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Blood Phenylalanine Levels	Day 1 up to 52 weeks after EOT (up to 91 weeks)
Maximum Observed Effect (Emax)	Day 1 up to 52 weeks after EOT (up to 91 weeks)
Area Under the Effect Versus Time Curve (AUEC)	Day 1 up to 52 weeks after EOT (up to 91 weeks)
Maximum Observed Concentration (Cmax)	Day 1 through Day 15 for Dose 1 and Dose 12
Area Under the Plasma Concentration-Time Curve (AUC)	Day 1 through Day 15 for Dose 1 and Dose 12
Number of Participants with Anti-Polyethylene Glycol Antibodies	Day 1 up to 52 weeks after EOT (up to 91 weeks)

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): March 29, 2024
• Primary Completion (Estimated): August 10, 2026
• Study Completion (Estimated): August 5, 2027

Study Registration Dates

• First Submitted: November 18, 2023
• First Submitted That Met QC Criteria: November 18, 2023
• First Posted (Actual): November 28, 2023

Study Record Updates

• Last Update Posted (Actual): October 22, 2024
• Last Update Submitted That Met QC Criteria: October 20, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Nervous System Diseases; Central Nervous System Diseases; Brain Diseases; Metabolic Diseases; Phenylketonuria; Phenylalanine; mRNA-3210; Autosomal recessive genetic disorder; In-born errors of metabolism; Rare metabolic disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Amino Acid Metabolism, Inborn Errors; Phenylketonurias
• Other Study ID Numbers: mRNA-3210-P101; 2023-506963-32-00 (Other Identifier: EU-CT Number)

Drug and device information, study documents

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