Health TrialsbyHealthPanel

Open-Label Study of mRNA-3927 in Participants With Propionic Acidemia

ConditionPropionic Acidemia
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
AgeNot listed
SponsorModernaTX, Inc.

About this trial

This 3-part, Phase 1/2 study is designed to characterize the safety, tolerability, and pharmacological activity (as assessed by biomarker measurements) and to determine the selected dose of mRNA-3927 in participants with genetically confirmed propionic acidemia (PA). After establishing a dose with an acceptable safety and pharmacodynamic (PD) response for participants ≥1 year of age in Part 1, participants will be enrolled in Part 2 (which will serve as the pivotal study) to allow for determination of the efficacy, safety, and PD of mRNA-3927. Part 3 will evaluate the safety, efficacy and PD response of mRNA-3927 in infants (\<1 year of age).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

≥ 8 years of age at the time of consent/assent if enrolled as 1 of the first 2 participants in Part 1.

≥1 year of age at the time of consent/assent if enrolled after the first 2 participants in Part 1.

Confirmed diagnosis of PA based on diagnosis by molecular genetic testing via central laboratory (PCCA and/or PCCB mutations).

Part 2 only: At least one documented MDE in the 12-month period before consent.

Disqualifiers

Any individual with laboratory abnormalities considered to be clinically significant (for example, markedly out of range, associated with clinical symptoms) in the Investigator or Sponsor's opinion that could interfere with or limit the participation in the study.

Estimated glomerular filtration rate (eGFR) <30 milliliters (mL)/minute/1.73 square meter (m²) for participants of all ages receiving chronic dialysis.

History of organ transplantation or planned organ transplantation during the period of study participation.

Corrected QT interval (QTc) >480 milliseconds (ms) using Bazett's correction.

Trial design

Design model

Sequential

Treatments tested in this trial

  • mRNA-3927

    Biological/Vaccine

    mRNA-3927 dispersion for IV infusion

Treatment groups

77 Participants
are divided into 1 treatment group
Group A: Part 1 (Dose Optimization), Part 2 (Pivotal Study), and Part 3 (Infants)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Part 1: Number of Participants with Treatment-emergent Adverse Event (TEAE), Serious Adverse Events (SAE) and TEAEs Leading to Discontinuation

Time frame
Day 1 (initial mRNA-3927 dose) up to Week 150 (End of Study)
2

Part 2: Change in Annualized Frequency of Clinical Event Committee (CEC)-adjudicated Metabolic Decompensation Events (MDEs) During 12-month Treatment Period With mRNA-3927 Compared to Annualized Frequency of CEC-adjudicated MDE During Pretreatment Period

Time frame
Pretreatment period (12 months before consent to first mRNA-3927 dose in the study) up to Month 12
3

Part 3: Number of Participants with TEAEs, SAEs, Adverse Events (AEs) of Special Interest (AESIs) and TEAEs Leading to Discontinuation

Time frame
Day 1 up to Week 73

Secondary outcomes

1

Part 1: Change From Baseline in Plasma 2-Methylcitrate (2-MC) and 3-Hydroxypropionic Acid (3-HP) Levels After Single and Repeated Administrations of mRNA-3927

Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

Time frame
Baseline up to Week 40
2

Part 1: Maximum Observed Effect (Emax) of 2-MC and 3-HP After Single and Repeated Administrations of mRNA-3927

Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

Time frame
Baseline up to Week 40
3

Part 1: Area Under the Effect Versus Time Curve (AUEC) of 2-MC and 3-HP After Single and Repeated Administrations of mRNA-3927

Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

Time frame
Baseline up to Week 40
4

Part 1: Duration of Response (DOR) After Single and Repeated Administrations of mRNA-3927

Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

Time frame
Baseline up to Week 40

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

ModernaTX, Inc.

Lead sponsor

Source ClinicalTrials.gov
Apply now