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

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

Official Title
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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

Conditions
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Phenylketonuria

Intervention / Treatment
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* Drug: mRNA-3210


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-3210<br>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<br>* IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA-3210, Autosomal recessive genetic disorder, Central Nervous System Diseases, Nervous System Diseases, Brain Diseases, Metabolic Diseases, Phenylketonuria, In-born errors of metabolism, Phenylalanine, Rare metabolic disease