We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04159103
Recruitment Status : Recruiting
First Posted : November 12, 2019
Last Update Posted : November 1, 2022
Sponsor:
Information provided by (Responsible Party):
ModernaTX, Inc.

Brief Summary:
This First-in-Human (FIH) Phase 1/2 study will evaluate mRNA-3927 in participants 1 year of age and older with genetically confirmed propionic acidemia (PA). The study is designed to characterize baseline biomarker levels followed by assessment of safety, pharmacokinetics (PK), and pharmacodynamics (PD) of different doses of mRNA-3927 in participants affected by PA as part of the Dose Optimization phase.

Condition or disease Intervention/treatment Phase
Propionic Acidemia Biological: mRNA-3927 Phase 1 Phase 2

Detailed Description:

During the Dose Optimization Stage, after each dose cohort is fully enrolled, and the dose-limiting toxicity (DLT) observation window of at least 14 days is complete for the final participant in that cohort, the Sponsor will review the totality of available safety data in conjunction with all available PK/PD data. Based on this review, the Sponsor will recommend a revised dose and/or dosing interval. The Sponsor will abide by predefined constraints as to the maximum percentage change in dose and dose interval. A maximum of 5 cohorts will be enrolled into the study.

Upon establishment of a dose with acceptable safety and pharmacodynamic activity, additional participants will be enrolled in a Dose Expansion Stage to allow for further characterization of the safety and pharmacodynamics of mRNA-3927.

Participants in both phases of study will participate in a predosing observational period, followed by a treatment period, and then a follow-up period after withdrawal of treatment.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Global, Phase 1/2, Open-Label, Dose Optimization Study to Evaluate the Safety, Pharmacodynamics, and Pharmacokinetics of mRNA-3927 in Participants With Propionic Acidemia
Actual Study Start Date : April 15, 2021
Estimated Primary Completion Date : March 5, 2025
Estimated Study Completion Date : January 6, 2027


Arm Intervention/treatment
Experimental: Dose Optimization Stage: Dose Level 1
Participants will receive 1 dose of Dose Level 1 of mRNA-3927 by intravenous (IV) infusion on Day 1 of a 21-day period for up to 10 doses during the approximate 30-week Treatment Period.
Biological: mRNA-3927
mRNA-3927 dispersion for IV infusion

Experimental: Dose Optimization Stage: Dose Level 2
Participants will receive 1 dose of Dose Level 2 of mRNA-3927 by IV infusion once every 2 weeks during the approximate 20-week Treatment Period.
Biological: mRNA-3927
mRNA-3927 dispersion for IV infusion

Experimental: Dose Optimization Stage: Dose Level 3
Participants will receive 1 dose of Dose Level 3 of mRNA-3927 by IV infusion once every 2 weeks during the approximate 20-week Treatment Period.
Biological: mRNA-3927
mRNA-3927 dispersion for IV infusion

Experimental: Dose Optimization Stage: Dose Level 4
Participants will receive 1 dose of Dose Level 4 of mRNA-3927 by IV infusion at an applicable dosing schedule during the approximate 20-40 week Treatment Period (20 weeks for every two week dosing, 30 weeks for every three week dosing, or 40 weeks for every four week dosing).
Biological: mRNA-3927
mRNA-3927 dispersion for IV infusion

Experimental: Dose Optimization Stage: Dose Level 5
Participants will receive 1 dose of Dose Level 5 of mRNA-3927 by IV infusion at an applicable dosing schedule during the approximate 20-40 week Treatment Period (20 weeks for every two week dosing, 30 weeks for every three week dosing, or 40 weeks for every four week dosing).
Biological: mRNA-3927
mRNA-3927 dispersion for IV infusion

Experimental: Dose Expansion Stage
Participant will receive the optimal dose of mRNA-3927 identified during the Dose Optimization Stage at 1 dose at an applicable dosing schedule during the approximate 20-40 week Treatment Period (20 weeks for every two week dosing, 30 weeks for every three week dosing, or 40 weeks for every four week dosing).
Biological: mRNA-3927
mRNA-3927 dispersion for IV infusion




Primary Outcome Measures :
  1. Number of Participants with an Adverse Event (AE) [ Time Frame: Day 1 (initial mRNA-3927 dose) up to Week 150 (End of Study) ]

Secondary Outcome Measures :
  1. Maximum Observed Concentration (Cmax) after Administration of mRNA-3927 [ Time Frame: Day 1 through Day 15 ]
    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

  2. Time of Cmax (Tmax) [ Time Frame: Day 1 through Day 15 ]
    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

  3. Area Under the Plasma Concentration-Time Curve (AUC) [ Time Frame: Day 1 through Day 15 ]
    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

  4. Frequency of Anti-Polyethylene Glycol Antibodies [ Time Frame: Baseline through Week 150 ]
  5. Change from Baseline in Plasma 2-Methylcitrate (2-MC) Levels at Week 40 [ Time Frame: Baseline (Week -3), Week 40 ]
    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927.

  6. Change from Baseline in Plasma 3-Hydroxypropionic Acid (3-HP) Levels at Week 40 [ Time Frame: Baseline (Week -3), Week 40 ]
    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927.

  7. Change from Baseline in Plasma 2-Methylcitrate (2-MC) Levels at Week 36 [ Time Frame: Baseline (Week -3), Week 36 ]
    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927.

  8. Change from Baseline in Plasma 3-Hydroxypropionic Acid (3-HP) Levels at Week 36 [ Time Frame: Baseline (Week -3), Week 36 ]
    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant must be ≥ 8 years of age at the time of consent/assent if enrolled as 1 of the first 2 participants.
  • Participant must be ≥1 year of age at the time of consent/assent if enrolled after the first 2 participants.
  • Confirmed diagnosis of propionic acidemia based on diagnosis by molecular genetic testing (propionyl-CoA carboxylase subunit α [PCCA] and/or propionyl CoA carboxylase subunit β [PCCB] mutations)

Exclusion Criteria:

  • Estimated glomerular filtration rate <30 milliliters (mL)/minute/1.73 square meter (m^2) as estimated by Schwartz formula for participants < 18 years of age or the Chronic Kidney Disease Epidemiology Collaboration creatinine based formula for participants ≥ 18 years of age or 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.
  • COVID-19 vaccination (generally 2 doses or a booster) within 6 weeks between their last COVID-19 vaccination dose and first study drug administration.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04159103


Contacts
Layout table for location contacts
Contact: Moderna Clinical Trials Support Center 1-877-777-7187 clinicaltrials@modernatx.com

Locations
Layout table for location information
United States, California
David Geffen School of Medicine UCLA Recruiting
Los Angeles, California, United States, 90095
Contact: Rosemary Silva-Garcia       rsilvagarcia@mednet.ucla.edu   
United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact       hvernon1@jhmi.edu   
Principal Investigator: Hilary Vernon         
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact    617-355-6394    Walla.Al-Hertani@childrens.harvard.edu   
Principal Investigator: Walla Al-Hertani         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
United States, New York
Icahn School of Medicine at Mount Sinai - Clinical Research Unit Recruiting
New York, New York, United States, 10029
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Ming Xu       mingfen.xu@duke.edu   
United States, Ohio
Cincinnati Children's Hospital Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Racheal Powers       Racheal.Powers@cchmc.org   
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Rebecca Madden       maddenr@chop.edu   
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Alyssa Tran       alyssat@bcm.edu   
Canada, Ontario
Hospital For Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Ashley Wilson       ashley.wilson@sickkids.ca   
United Kingdom
University Hospital Birmingham NHS Foundation Trust Recruiting
Birmingham, United Kingdom, B15 2TH
Contact: Vishy Veeranna       Vishy.veeranna@uhb.nhs.uk   
Birmingham Children's Hospital Recruiting
Birmingham, United Kingdom, B4 6NH
Contact    4.40121E+12    s.santra@nhs.net   
Principal Investigator: Saikat Santra         
Great Ormond Street Hospital (GOSH) Recruiting
London, United Kingdom, WC1N 3JH
Contact       Stephanie.Grunewald@gosh.nhs.uk   
Principal Investigator: Stephanie Grunewald         
Sponsors and Collaborators
ModernaTX, Inc.
Layout table for additonal information
Responsible Party: ModernaTX, Inc.
ClinicalTrials.gov Identifier: NCT04159103    
Other Study ID Numbers: mRNA-3927-P101
First Posted: November 12, 2019    Key Record Dates
Last Update Posted: November 1, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ModernaTX, Inc.:
mRNA-3927
Propionic Aciduria
Metabolism, Inborn Errors
Genetic Diseases
Inborn Amino Acid Metabolism, Inborn Errors
Acidosis
Acid-Base Imbalance
Metabolic Diseases
Organic Acidemias
Moderna
mRNA
Additional relevant MeSH terms:
Layout table for MeSH terms
Propionic Acidemia
Acidosis
Acid-Base Imbalance
Metabolic Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn