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

Launched by MODERNATX, INC. · Nov 7, 2019

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called mRNA-3927 for people with propionic acidemia (PA), a rare genetic disorder that affects how the body breaks down certain proteins and fats. The trial is divided into three parts. In the first part, researchers will find a safe and effective dose of mRNA-3927 for participants aged 1 year and older. After that, they will invite more participants to help understand how well the treatment works and its safety. The third part will focus on infants under 1 year old who have PA.

To be eligible for this study, participants must have a confirmed diagnosis of propionic acidemia through genetic testing. For older children, they need to be at least 1 year old, while infants can join if they showed signs of PA shortly after birth or have a sibling with the condition. Participants can expect close monitoring and evaluation of their health during the trial. It's important to know that individuals with certain health problems or serious conditions may not be able to participate in this study for safety reasons.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• Participants ≥1 year of age are eligible to be included in the study only if all of the following criteria apply:
• • ≥ 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.
• Participants \<1 Year of Age :
• • Identification by newborn screening shortly after birth or having suspected PA by presenting with a spectrum of metabolic symptoms, and having a sibling diagnosed with PA. Participant may enter the Screening Period while awaiting genetic testing results, provided that all other eligibility criteria are met but would not be enrolled until diagnosis of PA is confirmed.
• • For infants in the neonatal intensive care unit (NICU) only: ≥37 weeks gestational age at the time of birth without other conditions/comorbidities that in the opinion of the Investigator may interfere with the interpretation of study results.
• • Body weight ≥3 kilograms (kg) at Screening.
• * At least 1 documented PA-related event prior to Screening defined as the following criteria:
• • Clinical signs of metabolic deterioration consistent with PA (for example, vomiting, not feeding well/poor suck, heavy breathing, lethargy, absence of proper perfusion, abnormal movements including bicycling, abnormal tone, low body temperature, seizure\[s\]), OR
• • Meeting the criteria of MDE definition, OR
• * Evidence of laboratory abnormalities as evidenced by at least one of the following:
• • Metabolic acidosis with elevated anion gap.
• • Acute hyperammonemia.
• • Neutropenia or thrombocytopenia.
• Exclusion Criteria:
• Participants of all ages are excluded from the study if during Screening any of the following criteria apply:
• • 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 (m\^2) 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.
• • Grade 3 or 4 heart failure according to the Modified Ross Heart Failure Classification for Children or the New York Heart Association Classification.
• • Pregnant or breastfeeding.
• • Other clinically significant conditions that in the Investigator's opinion could interfere with the safety of the participant, the interpretation of study results, or limit the participation in the study.