Active clinical trials for "Amino Acid Metabolism, Inborn Errors"

This is an interventional study to assess the safety, PK, and efficacy of HST5040 in 12 subjects - 6 with Methylmalonic Acidemia (MMA) and 6 with Propionic Acidemia (PA). The study consists of 3 parts: Part A: Open-label, within-subject, dose escalation study in PA and MMA subjects ≥ 2 years old to identify a safe and pharmacologically active (optimal) dose of HST5040 for use in Part B. Subjects will continue in a Part A open-label extension until all subjects complete Part A and the optimal dose of HST5040 is identified for use in Part B. Part B: 6-month, randomized, double-blind, placebo-controlled, 2-period crossover in the same subjects from Part A to evaluate safety and efficacy of the optimal dose of HST5040 in addition to standard of care (SoC). Part C: open-label long-term extension study in PA and MMA subjects ≥ 2 years old (N = approximately 12, 6 each) to evaluate the long-term safety and efficacy of the optimal dose of HST5040. This study will determine whether HST5040 can improve levels of disease-associated toxins that accumulate in patients with PA and MMA.

The purpose of this study is to assess the safety, tolerability, PK and PD of BBP-671 in healthy volunteers and patients with Propionic Acidemia or Methylmalonic Acidemia.

This is a study of mRNA-3705 in participants with isolated elevated methylmalonic acid (MMA) due to methylmalonyl-coenzyme A (CoA) mutase (MUT) deficiency. The main goal of the study is to assess safety, pharmacokinetics, and pharmacodynamics of mRNA-3705.

The overall objective of this study is to determine the safety and efficacy of AAV2-hAADC delivered to the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) in children with aromatic L-amino acid decarboxylase (AADC) deficiency.

Urea cycle disorders (UCD) are a group of rare inherited metabolism disorders. Infants and children with UCD commonly experience episodes of vomiting, lethargy, and coma. The purpose of this study is to perform a long-term analysis of a large group of individuals with various UCDs. The study will focus on the natural history, disease progression, treatment, and outcome of individuals with UCD.

To obtain short-term and long-term clinical safety information, in pediatric and adult patients with PA and MMA treated with Carbaglu®.

The JUMP (Journey to Understand MMA and PA) Study is being conducted by HemoShear Therapeutics and AllStripes, a rare disease online research platform. JUMP is designed to accelerate understanding of the natural course of methylmalonic acidemia (MMA) and propionic acidemia (PA) disease and treatment for families, researchers, clinicians and industry. The study will collect and provide patient medical record information from multiple institutions for families to access in one place at no cost. AllStripes will remove identifying information like name and address from these medical records and aggregate this data for the HemoShear team to better understand the medical experience and progression of MMA and PA over time. In addition, academic researchers, healthcare practitioners and patient advocacy groups can apply to use the collective patient community data to answer specific research questions at no cost. HemoShear is collecting natural history data on MMA and PA because the company needs insight into the real-world experience of many patients to better understand the disease and be able to scientifically demonstrate whether the potential new treatment they are developing is effective in improving outcomes. This natural history study will include retrospective and prospective components. The retrospective component will consist of data abstracted from primarily electronic health records (eHR) and some paper records. The prospective component will include ongoing collection of medical records from enrolled participants, and participants may opt in to complete health-related questionnaires and an optional genetic testing sub-study. After signing informed consent, participants or their legal guardians will grant permission to AllStripes to collect their health records for data abstraction. Participants may opt into an optional no cost genetic testing sub-study. The JUMP (Journey to Understand MMA and PA) sub-study will help assess whether the genetic variant of the affected person may relate to disease severity and treatment response. Getting genetic testing will enable participants to understand the genetic mutation that causes their type of methylmalonic acidemia (MMA) or propionic acidemia (PA). Knowing the genetic mutations (whether from the MMUT, MMAA or MMAB gene or PCCA or PCCB) can help the impacted person, their caregivers and healthcare professionals understand the potential course of disease and select approaches to better manage the disease. The additional information will enable HemoShear and AllStripes to understand whether different genetic variants impact the disease journey and outcomes. A separate informed consent will be obtained for participating in the sub-study.

This Phase 1/2 study will evaluate the safety and pharmacodynamics (PD) of SEL-302, which consists of the gene transfer vector MMA-101 following administration of an immunomodulatory SEL-110 agent in pediatric subjects with Methylmalonyl-CoA Mutase (MMUT) MMA.

The objective of this study is to obtain short- and long-term clinical safety data in pediatric and adult patients with PA and MMA treated with Carbaglu, including pregnancy and fetal outcomes. This is an observational/non-interventional study. Patients will be treated per the prescribing information and routine medical practice. Only available data will be collected as part of the study.

Methylmalonic acidemia (MMA), one of the most common inborn errors of organic acid metabolism, is heterogeneous in etiology and clinical manifestations. Affected patients with cblA, cblB and mut classes of MMA are medically fragile and can suffer from complications such as metabolic stroke or infarction of the basal ganglia, pancreatitis, end stage renal failure, growth impairment, osteoporosis, and developmental delay. The frequency of these complications and their precipitants remain undefined. Furthermore, current treatment protocol outcomes have continued to demonstrate substantial morbidity and mortality in the patient population. Increasingly, solid organ transplantation (liver, and/or kidney) has been used to treat patients. Disordered transport and intracellular metabolism of vitamin B12 produces a distinct group of disorders that feature methylmalonic acidemia as well as (hyper)homocysteinemia. These conditions are named after the corresponding cellular complementation class (cblC, cblD, cblF, cblJ and cblX) and are also heterogenous, clinically and biochemically. The genetic disorders underlying cblE and cblG feature an isolated impairment of the activity of methionine synthase, a critical enzyme involved in the conversion of homocysteine to methionine and these disorders feature (hyper)homocysteinemia. Lastly, a group of patients can have increased methylmalonic acid and/or homocysteine in the blood or urine caused by variant(s)in recently identified (ACSF3) and unknown genes. In this protocol, we will clinically evaluate patients with methylmalonic acidemia and cobalamin metabolic defects. Routine inpatient admissions will last up to 4-5 days and involve urine collection, blood drawing, ophthalmological examination, radiological procedures, MRI/MRS, skin biopsies in some, and developmental testing. In a subset of patients who have or will receive renal, hepato- or hepato-renal transplants or have an unusual variant or clinical course and have MMA, a lumbar puncture to examine CSF metabolites will be performed. In this small group of patients, CSF metabolite monitoring may be used to adjust therapy. The study objectives will be to further delineate the spectrum of phenotypes and characterize the natural history of these enzymopathies, query for genotype/enzymatic/phenotype correlations, search for new genetic causes of methylmalonic acidemia and/or homocysteinemia, identify new disease biomarkers and define clinical outcome parameters for future clinical trials. The population will consist of participants previously evaluated at NIH, physician referrals, and families directed to the study from clinicaltrials.gov as well as the Organic Acidemia Association, Homocystinuria Network America and other national and international support groups. Most participants will be evaluated only at the NIH Clinical Center. However, if the NIH team decides that a patient under the age of 2 years is a candidate subject for this research protocol, that patient may enroll at the Children s National Medical Center (CNMC) site, pending approval by Dr Chapman, the Principal Investigator of the CNMC location Individuals may also enroll in the tissue collection only part of the study at the UPMC Children s Hospital of Pittsburgh or share medical history and clinical data via telemedicine visits remotely. Outcome measures will largely be descriptive and encompass correlations between clinical, biochemical and molecular parameters.