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

Propionic Acidemia Clinical Trial

— PROTECT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04176523
• Other study ID #: 17180
• Status: Recruiting
• Start date: January 15, 2019
• Est. completion date: July 30, 2029

Study information

• Verified date: February 2024
• Source: Recordati Rare Diseases
• Contact: Vincenzo Giordano, MD
• Phone: 33 1 79911282
• Email: giordano.v[@]recordati.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 95
• Est. completion date: July 30, 2029
• Est. primary completion date: December 30, 2024
• Gender: All
• Age group: 6 Months to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Acidosis
• Methylmalonic Acidemia
• Propionic Acidemia

Intervention

Drug:
• Carglumic Acid
Maintenance therapy with carglumic acid

Locations

Country	Name	City	State
France	Hopital Des Enfants, CHU de Bordeaux-GH Pellegrin	Bordeaux
France	Hopital de la Conception	Marseille
France	Hôpital de la Timone	Marseille
France	CHU de Nancy - Hopitaux de Brabois	Nancy
France	Hôpital Necker Enfants Malades	Paris
France	CHU de Rouen	Rouen
France	Hopital de Hautepierre	Strasbourg
France	Nouvel Hopital Civil	Strasbourg
Germany	Klinikum Bremen Mitte, Prof. Hess Kinderklinik	Bremen
Italy	Azienda Ospedaliero Universitaria Meyer	Firenze
Italy	Milan Policlinico University	Milan
Italy	San Paola Hospital, ASST Santi Paolo e Carlo	Milan
Italy	Azienda Ospedaliera San Gerardo Monza	Monza
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	University Hospital of Padova	Padova
Italy	Turin University Hospital	Turin
Norway	Oslo University Hospital	Oslo
Spain	AMM hospital val d'hebron	Barcelona
Spain	Sant Joan de Deu	Barcelona
Spain	Universitario de Cruces	Bilbao
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Infantil Universitario Nino Jesus	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Universitario Ramon y Cajal Madrid	Madrid
Spain	Hospital Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital Universitario Son Espases	Palma De Mallorca
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Universitario Miguel Servet	Zaragoza
Sweden	NÄL	Trollhattan
United Kingdom	Great Ormond Street Hospital	London
United Kingdom	Guy's and St. Thomas' Hospital NHS Foundation Trust	London
United Kingdom	Sheffield Children's Hospital NHS Foundation Trust	Sheffield

Sponsors (1)

Lead Sponsor	Collaborator
Recordati Rare Diseases

Countries where clinical trial is conducted

France,  Germany,  Italy,  Norway,  Spain,  Sweden,  United Kingdom, 

References & Publications (7)

Alfadhel M, Nashabat M, Saleh M, Elamin M, Alfares A, Al Othaim A, Umair M, Ahmed H, Ababneh F, Al Mutairi F, Eyaid W, Alswaid A, Alohali L, Faqeih E, Almannai M, Aljeraisy M, Albdah B, Hussein MA, Rahbeeni Z, Alasmari A. Long-term effectiveness of carglumic acid in patients with propionic acidemia (PA) and methylmalonic acidemia (MMA): a randomized clinical trial. Orphanet J Rare Dis. 2021 Oct 11;16(1):422. doi: 10.1186/s13023-021-02032-8. — View Citation

Burlina A, Bettocchi I, Biasucci G, Bordugo A, Gasperini S, La Spina L, Maines E, Meli C, Menni F, Paci S, Procopio E, Rossi A, Rubert L, Spada M, Tubili F, Tummolo A. Long-term use of carglumic acid in methylmalonic aciduria, propionic aciduria and isovaleric aciduria in Italy: a qualitative survey. Eur Rev Med Pharmacol Sci. 2022 Jul;26(14):5136-5143. doi: 10.26355/eurrev_202207_29302. — View 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. — View Citation

Kido J, Matsumoto S, Nakamura K. Carglumic Acid Contributes to a Favorable Clinical Course in a Case of Severe Propionic Acidemia. Case Rep Pediatr. 2020 Mar 9;2020:4709548. doi: 10.1155/2020/4709548. eCollection 2020. — View Citation

Kiykim E, Oguz O, Duman C, Zubarioglu T, Cansever MS, Zeybek ACA. Long-term N-carbamylglutamate treatment of hyperammonemia in patients with classic organic acidemias. Mol Genet Metab Rep. 2021 Jan 30;26:100715. doi: 10.1016/j.ymgmr.2021.100715. eCollection 2021 Mar. — View 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. — View 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 Jan 10. doi: 10.1007/s40268-023-00449-z. Online ahead of print. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Caregiver Burden Exposure Frequency and Duration	description of the patient and caregiver burden associated with MMA and PA	18 months
Secondary	Caregiver Satisfaction Level	Describe the MMA and PA patient and caregiver satisfaction with MMA or PA treatment	18 months
Secondary	Maintenance Dosage of NCG	Document the dosages of NCG used in maintenance treatment	54 months