Clinical trial NCT06147856: A Dose-finding Study to Evaluate mRNA-3210 in Participants With Phenylketonuria
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Phenylketonuria
Keywords: 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
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2023-11-28
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to 52 weeks after EOT (up to 91 weeks)
Secondary outcomes:
measure: Change from Baseline in Blood Phenylalanine Levels
timeFrame: Day 1 up to 52 weeks after EOT (up to 91 weeks)
measure: Maximum Observed Effect (Emax)
timeFrame: Day 1 up to 52 weeks after EOT (up to 91 weeks)
measure: Area Under the Effect Versus Time Curve (AUEC)
timeFrame: Day 1 up to 52 weeks after EOT (up to 91 weeks)
measure: Maximum Observed Concentration (Cmax)
timeFrame: Day 1 through Day 15 for Dose 1 and Dose 12
measure: Area Under the Plasma Concentration-Time Curve (AUC)
timeFrame: Day 1 through Day 15 for Dose 1 and Dose 12
measure: Number of Participants with Anti-Polyethylene Glycol Antibodies
timeFrame: Day 1 up to 52 weeks after EOT (up to 91 weeks)
Other outcomes:
Locations:
Study officials:
References: