Clinical trial NCT04176523: Understanding the Long-Term Management of Organic Acidemia Patients With CARBAGLU®: A Mixed Methods Approach
Official title: Understanding the Long-Term Management of Organic Acidemia Patients With CARBAGLU®: A Mixed Methods Approach
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Methylmalonic Acidemia
Propionic Acidemia
Lead sponsor: Recordati Rare Diseases
Sponsor class: INDUSTRY
First posted: 2019-11-25
Enrollment: 95
Sex: ALL
Minimum age (years): 6
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with organic acideamia that have been on treatment with CARBAGLU® for a minimum of six months for the long-term management of their disease. This prospective observational study population will include up to 95 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.

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Patient has confirmed diagnosis of an organic acidemia (e.g., MMA or PA)
2. Patient initiated treatment with carglumic acid for long-term management of MMA or PA
3. Patient has been treated with carglumic acid for a minimum of 6 months
4. Patient (or caregiver) is able to comply with all prospective study procedures
5. Patient (or caregiver) is able to provide informed consent

Exclusion Criteria:

* None

Primary outcomes:
measure: Change in Number and Duration of Decompensation Events
timeFrame: 54 months
Secondary outcomes:
measure: Frequency and Duration of Healthcare Resource Utilization
timeFrame: 18 months
measure: Caregiver Burden Exposure Frequency and Duration
timeFrame: 18 months
measure: Caregiver Satisfaction Level
timeFrame: 18 months
measure: Maintenance Dosage of NCG
timeFrame: 54 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Hopital Des Enfants, CHU de Bordeaux-GH Pellegrin
city: Marseille
country: France
facility: Hopital de la Conception
city: Marseille
country: France
facility: Hôpital de la Timone
city: Nancy
country: France
facility: CHU de Nancy - Hopitaux de Brabois
city: Paris
country: France
facility: Hôpital Necker Enfants Malades
city: Rouen
country: France
facility: CHU de Rouen
city: Strasbourg
country: France
facility: Nouvel Hopital Civil
city: Strasbourg
country: France
facility: Hopital de Hautepierre
city: Bremen
country: Germany
facility: Klinikum Bremen Mitte, Prof. Hess Kinderklinik
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Meyer
city: Milan
country: Italy
facility: San Paola Hospital, ASST Santi Paolo e Carlo
city: Milan
country: Italy
facility: Milan Policlinico University
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo Monza
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Padova
country: Italy
facility: University Hospital of Padova
city: Turin
country: Italy
facility: Turin University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Barcelona
country: Spain
facility: AMM hospital val d'hebron
city: Barcelona
country: Spain
facility: Sant Joan de Deu
city: Bilbao
country: Spain
facility: Universitario de Cruces
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Universitario Ramon y Cajal Madrid
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Zaragoza
country: Spain
facility: Universitario Miguel Servet
city: Trollhattan
country: Sweden
facility: NÄL
city: London
country: United Kingdom
facility: Guy's and St. Thomas' Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital NHS Foundation Trust
Study officials:
affiliation: Sheffield Children's NHS Trust
name: Sufin Yap, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Tummolo A, Melpignano L, Carella A, Di Mauro AM, Piccinno E, Vendemiale M, Ortolani F, Fedele S, Masciopinto M, Papadia F. Long-term continuous N-carbamylglutamate treatment in frequently decompensated propionic acidemia: a case report. J Med Case Rep. 2018 Apr 22;12(1):103. doi: 10.1186/s13256-018-1631-1.
citation: Burlina A, Cazzorla C, Zanonato E, Viggiano E, Fasan I, Polo G. Clinical experience with N-carbamylglutamate in a single-centre cohort of patients with propionic and methylmalonic aciduria. Mol Genet Metab Rep. 2016 Jul 13;8:34-40. doi: 10.1016/j.ymgmr.2016.06.007. eCollection 2016 Sep.
citation: Yap S, Lamireau D, Feillet F, Ruiz Gomez A, Davison J, Tangeraas T, Giordano V. Real-World Experience of Carglumic Acid for Methylmalonic and Propionic Acidurias: An Interim Analysis of the Multicentre Observational PROTECT Study. Drugs R D. 2024 Mar;24(1):69-80. doi: 10.1007/s40268-023-00449-z. Epub 2024 Jan 10.