Understanding the Long-Term Management of Organic Acidemia Patients With CARBAGLU®: A Mixed Methods Approach

Study Overview
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Brief Summary
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This is a prospective mixed-design study focused on the long-term management of propionic aciduria (PA) and methylmalonic aciduria (MMA) with N-carbamylglutamate (NCG) maintenance therapy. Treatment characteristics, clinical outcomes, and healthcare utilization data of patients diagnosed PA or MMA treated >6 months therapy with NCG are collected at baseline, 12 months, 18 months, 36 months and 54 months. Qualitative interviews with adult patients and caregivers are conducted >6 months after study enrollment to gain a better understanding of the disease burden and the treatment burden of patients and their families.

Detailed Description
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Study Design: This is a prospective, longitudinal, observational study of patients diagnosed with organic acidemia that has been on treatment with carglumic acid for a minimum of six months for the long-term management of their disease. This prospective observational study population will include up to 85 diagnosed MMA or PA patients with current carglumic acid treatment experience from 6 European countries: Sweden, the United Kingdom (UK), the Netherlands, Germany, Norway, Italy, Spain and France. The patients (or caregivers) included in this prospective observational study will also be invited to participate in a one-on-one phone interview. Study Procedures: After Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approval is obtained for the protocol and all supporting protocol documents, clinicians caring for patients with MMA or PA will provide their patients (or caregivers) with the opportunity to participate in the study. Patients (or caregivers) will receive an Information Letter (PIL) (Appendices A and B) inviting them (or their caregiver) to take part in a prospective observational study and in a one-on-one phone interview. Patients (or caregivers) who are interested in participating in this observational/interview study will review the informed consent form (Appendices C and D) with the clinician and his/her research team. If agreeable, patients (or caregivers) will be asked to sign the consent form and a countersigned copy will be provided to them for their records. Clinicians and their research team at each site will then review patient charts and record demographic and medical history information for each patient. Patient information from medical charts will be collected at the start of the study (baseline), and 12 months and 18 months, and 36 months, and 54 months after baseline. All information derived from medical chart reviews will be recorded through web-based Electronic Data Capture system (EDC). Patients (or caregivers) who agree to participate in a one-on-one phone interview will provide contact information for their clinicians and the respective research team to include in the Contact Information Form (CIF) (Appendix E). Researchers will then contact patients (or caregivers) directly to schedule a one-hour phone interview. An interview guide (Appendices F and G) including open-ended questions and probes will be used to elicit concepts and orient the discussion during the interview. Patient (or caregiver) interviews will focus on describing the symptoms and impacts of MMA or PA, as well as patient treatment experiences with carglumic acid, their treatment preferences, and their satisfaction with treatment. At the end of the interview, patients (or caregivers) will be asked to complete a Demographic and Health Information Form (DHIF; Appendices H and I). Phone interviews will be audio-recorded with the patient's (or caregiver) permission, transcribed and translated (as needed) in preparation for qualitative analysis. Data Analysis: The primary prospective data analysis will involve a comparison of the incidence and duration of decompensation episodes pre- and post- initiation of carglumic acid. Additional analysis will include healthcare resource utilization around individual decompensation events, patient/caregiver burden, and patient/caregiver satisfaction with treatment. All prospective data will be undertaken using SAS® software, version 9.4 of the SAS® system for Windows (Cary, NC, USA). All qualitative data from the interviews will be analyzed using ATLAS.ti, a software package uniquely designed to analyze qualitative data. The audio-recorded verbatim transcripts of the interviews will be coded to identify patterns in participants' responses concerning patient experiences with the symptoms and impacts of MMA or PA, treatment experience with carglumic acid, patient treatment preferences, and treatment satisfaction. Findings will be summarized in a final report and may be published or presented by the investigator(s) after the review by, and in consultation and agreement with, the sponsor. If published or presented, the results will be presented in such a way that confidential or proprietary information is not disclosed.

Official Title
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Understanding the Long-Term Management of Organic Acidemia Patients With CARBAGLU®: A Mixed Methods Approach

Conditions
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Methylmalonic Acidemia, Propionic Acidemia

Intervention / Treatment
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* Drug: Carglumic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has confirmed diagnosis of an organic acidemia (e.g., MMA or PA) Patient initiated treatment with carglumic acid for long-term management of MMA or PA Patient has been treated with carglumic acid for a minimum of 6 months Patient (or caregiver) is able to comply with all prospective study procedures Patient (or caregiver) is able to provide informed consent Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Methylmalonic_acidemia<br>Patients with confirmed diagnosis of methylmalonic acidemia, and treated with carglumic acid, at any dose form, any dosage, | Drug: Carglumic Acid<br>* Maintenance therapy with carglumic acid<br>* Other names: Carbaglu;|
| Propionic_Acidemia<br>Patients with confirmed diagnosis of propionic acidemia, and treated with carglumic acid, at any dose | Drug: Carglumic Acid<br>* Maintenance therapy with carglumic acid<br>* Other names: Carbaglu;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Number and Duration of Decompensation Events | Change in the number of decompensation events before and after treatment with carglumic acid | 54 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and Duration of Healthcare Resource Utilization | Estimation of the health care resource utilization associated with a decompensation event with number of inpatient hospitalization vs. outpatient vs. home. Treatment used to control ammonia levels during decompensation episodes. Number of emergency visits. number of visits to specialist or to general practitioner. Number of hospital stays. Number of bed days in hospital. | 18 months | 
| Caregiver Burden Exposure Frequency and Duration | description of the patient and caregiver burden associated with MMA and PA | 18 months | 
| Caregiver Satisfaction Level | Describe the MMA and PA patient and caregiver satisfaction with MMA or PA treatment | 18 months | 
| Maintenance Dosage of NCG | Document the dosages of NCG used in maintenance treatment | 54 months |