Authorised Phase I and Phase II (Integrated)- First administration to humans Propionic Acidemia

A study to investigate the safety and efficacy of mRNA-3927 in participants with genetically confirmed propionic acidemia

EU CTIS ID: 2022-502910-10-00

What this study is testing

Part 1: Evaluate the safety and tolerability of mRNA-3927 in participants with PA Part 2: Demonstrate the efficacy of mRNA-3927 as determined by reduction in frequency of MDEs Part 3: Evaluate the safety and tolerability of mRNA-3927

Phase I and Phase II (Integrated)- First administration to humans

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

Participants ≥1 Year of Age 1. ≥ 8 years of age at the time of consent/assent if enrolled as 1 of the first 2 participants in Part 1;
10. Body weight ≥3 kg at Screening
11. At least 1 documented PA-related event prior to Screening defined as the following criteria: • Clinical signs of metabolic deterioration consistent with PA (eg, 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.
12. Legally authorized representative is willing and able to provide informed consent as mandated by local regulations and willing and able to comply with study-related assessments.
2. ≥ 1 year of age at the time of consent/assent if enrolled after the first 2 participants in Part 1;
3. Confirmed diagnosis of PA based on diagnosis by MGT via central laboratory (PCCA and/or PCCB mutations);

You likely can't join if

1. Participants of all Ages. Any individual with laboratory abnormalities considered to be clinically significant (eg, 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;
2. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, as estimated by Schwartz formula for participants < 18 years of age (Schwartz et al 2012) or by the Chronic Kidney Disease Epidemiology Collaboration creatinine-based formula for participants ≥ 18 years of age or for participants of all ages receiving chronic dialysis;
3. QTc > 480 ms using Bazett's correction;
4. In female participants of reproductive potential, a positive pregnancy test;
5. Pregnant or breastfeeding;
6. Grade 3 or 4 heart failure according to the Modified Ross Heart Failure Classification for Children or the New York Heart Association Classification;

See the full eligibility criteria

Who can join

Participants ≥1 Year of Age 1. ≥ 8 years of age at the time of consent/assent if enrolled as 1 of the first 2 participants in Part 1;
10. Body weight ≥3 kg at Screening
11. At least 1 documented PA-related event prior to Screening defined as the following criteria: • Clinical signs of metabolic deterioration consistent with PA (eg, 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.
12. Legally authorized representative is willing and able to provide informed consent as mandated by local regulations and willing and able to comply with study-related assessments.
2. ≥ 1 year of age at the time of consent/assent if enrolled after the first 2 participants in Part 1;
3. Confirmed diagnosis of PA based on diagnosis by MGT via central laboratory (PCCA and/or PCCB mutations);
4. Participant and/or legally authorized representative is willing and able to provide informed consent and/or assent as mandated by local regulations and willing and able to comply with study-related assessments;
5. Sexually active females of childbearing potential and sexually active males of reproductive potential agree to use a highly effective method of contraception during study treatment and for 3 months following the last administration of mRNA-3927.
6. (Part 2 only) At least one documented MDE in the 12-month period before consent.
Participants <1 Year of Age 7. Identification by newborn screening shortly after birth or having suspected PA by presenting with a spectrum of metabolic symptoms (as defined by the criteria below), 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.
8. For infants in the 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. [Note: Infants <37 weeks gestational age who are no longer neonates at the time of Screening and are thriving independently are eligible].
9. <1 year of age at the time of first dose.

What rules you out

1. Participants of all Ages. Any individual with laboratory abnormalities considered to be clinically significant (eg, 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;
2. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, as estimated by Schwartz formula for participants < 18 years of age (Schwartz et al 2012) or by the Chronic Kidney Disease Epidemiology Collaboration creatinine-based formula for participants ≥ 18 years of age or for participants of all ages receiving chronic dialysis;
3. QTc > 480 ms using Bazett's correction;
4. In female participants of reproductive potential, a positive pregnancy test;
5. Pregnant or breastfeeding;
6. Grade 3 or 4 heart failure according to the Modified Ross Heart Failure Classification for Children or the New York Heart Association Classification;
7. History of organ transplantation or planned organ transplantation during the period of study participation;
8. Hypersensitivity to acetaminophen/paracetamol and/or ibuprofen or H1/H2 receptor blockers;
9. History of hypersensitivity to any component of the mRNA-3927;
18. Previously received gene therapy for PA.
10. History of anaphylaxis/anaphylactoid reaction or severe hypersensitivity with infusions;
11. Participation in another clinical study of another investigational agent within 30 days before study entry or within 5 elimination half-lives of the investigational agent, whichever is longer;
12. Major surgical procedure within 30 days before the Screening Visit (excludes central line, port, or feeding tube placement);
13. Enrollment in the study is not deemed to be of clinical benefit, in the opinion of the Investigator;
14. Other condition that in the Investigator's opinion could interfere with interpretation of study results or limit the participant's participation in the study;
15. No longer applicable.
16. (Part 2 only) History of hepatitis B (known positive HBsAg), HCV, or HIV (positive HIV-1/HIV-2 antibodies). Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg are eligible. Participants with history of positive results for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
17. 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.

The study team makes the final eligibility decision.

Where it's taking place

United States
United Kingdom
Japan
Canada
Saudi Arabia

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 0-17 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United States; United Kingdom; Japan; Canada; Saudi Arabia. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.