Clinical trial NCT03484767: "The MaP Study": Mapping the Patient Journey in MMA and PA
Official title: A Longitudinal, Exploratory, Natural History Study to Further Characterize and Describe the Signs and Symptoms of Patients With Organic Acidemias
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Methylmalonic Acidemia
Propionic Acidemia
Keywords: methylmalonic acidemia
MMA
organic acidemia
mut deficiency
inborn errors of metabolism
mut0
mut-
PA
PCCA
PCCB
propionic acidemia
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2018-04-02
Enrollment: 97
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals of any age with confirmed diagnosis of isolated MMA due to MUT deficiency (mut0 or mut-) or isolated PA

Brief summary: Longitudinal, exploratory, natural history study of patients with MMA due to mut deficiency and PA to characterize the changes in blood disease biomarkers over time and the frequency and severity of clinical events related to their disease.


Eligibility criteria: Inclusion Criteria:

MMA Only • Patient has a confirmed diagnosis of isolated MMA due to MUT deficiency (mut0 or mut-) based on the following criteria:

* Elevated plasma/serum/DBS or urine methylmalonic acid levels
* Presence of normal serum/plasma vitamin B12 and plasma homocysteine levels
* Confirmed by molecular genetic testing. Genetic testing can be performed after the administration of informed consent if not available, however, molecular genetic results must be confirmed before the second study visit

PA Only

• Patient has a confirmed diagnosis of isolated PA based on the following criteria:

* Elevated plasma/DBS/urine 2-MC and/or 3-HP
* Elevated plasma/serum/DBS propionylcarnitine (C3)
* Confirmed by genetic testing for mutations of the PCCA or PCCB genes. Genetic testing can be performed after the administration of informed consent if not available, however, molecular genetic results must be confirmed before the second study visit

Both MMA and PA

* Patient (and/or legally authorized representative as applicable to local regulations) is willing and able to comply with study-related assessments and activities
* Patient or legally authorized representative is willing and able to provide informed consent and/or assent as mandated by local regulation

Exclusion Criteria:

* Estimated GFR \<30 mL/min/1.73m2 based on age appropriate equations or patients who undergo chronic dialysis
* The patient is pregnant or lactating at the time of screening. (Note: Patients who become pregnant during the study may remain in the study) MMA Only
* Patients diagnosed with isolated MMA cblA, cblB, or cblD enzymatic subtypes or methylmalonyl-CoA epimerase deficiency or combined MMA with homocystinuria PA Only
* Patient has a confirmed diagnosis of multiple carboxylase deficiency

Primary outcomes:
measure: Change in plasma methylmalonic acid levels (MMA only)
timeFrame: Baseline through 12 months
measure: Frequency of disease related clinical events in enrolled participants (mut0 and mut- MMA patients)
timeFrame: Baseline through 12 months
measure: Changes in plasma 2-MC levels (PA only)
timeFrame: Baseline through 12 months
measure: Changes in plasma 3-HP levels (PA only)
timeFrame: Baseline through 12 months
measure: Frequency of disease related clinical events in enrolled participants (PA patients)
timeFrame: Baseline through 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Health Services
state: California
city: Atlanta
country: United States
facility: Emory Univeristy
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Marseille cedex 15
country: France
facility: Hôpital de la Timone
state: Bouches-du-Rhône
city: Paris cedex 15
country: France
facility: Hôpital Necker - Enfants Malades
state: Paris
city: Barakaldo
country: Spain
facility: Hospital de Cruces
state: Vizcaya
city: Bloomsbury
country: United Kingdom
facility: Great Ormond Street Hospital
state: Greater London
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Manchester
country: United Kingdom
facility: Manchester University Hospitals
Study officials:
References: