ClinicalTrials.gg
RecruitingNCT04176523PROTECTUpdated Feb 5, 2024

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

An observational study in Methylmalonic Acidemia and Propionic Acidemia, sponsored by Recordati Rare Diseases. Recruiting at 32 sites in 7 countries. Open to participants aged 6 Months to 99 Years. Per ClinicalTrials.gov, last updated 2024-02-05.

Sponsored by Recordati Rare Diseases (part of RECORDATI GROUP) · Observational

From the registry’s dates

  • Primary completion was expected by Dec 2024, 1 year 10 months ago, but the record still lists the study as recruiting.
  • Started Jan 2019; still recruiting 7 years 9 months later.
Study type
Observational
Model
Case-only
Time perspective
Prospective
Enrollment
95
Ages
6 Months to 99 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Methylmalonic Acidemia
  • Propionic Acidemia
03

In context

Methylmalonic acidemia

26 studies on the registry are indexed under Methylmalonic acidemia; 7 are open to participants now.

This study's planned enrollment of 95 is above the median of 30 across 11 observational studies indexed under Methylmalonic acidemia.

Browse Methylmalonic acidemia studies →

Lead sponsor

Recordati Rare Diseases is the lead sponsor of 3 studies on the registry; 2 are open to participants now.

First submitted after Recordati Rare Diseases became part of RECORDATI GROUP.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
6 Months to 99 Years
Sexes eligible
All
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.

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

Exclusion criteria

Exclusion Criteria:

  • None
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

05

Study design

Observational model
Case-only
Time perspective
Prospective
Enrollment
95 participants (estimated)
Patient registry
No

Groups and cohorts

  • Methylmalonic_acidemia

    Patients with confirmed diagnosis of methylmalonic acidemia, and treated with carglumic acid, at any dose form, any dosage,

    Drug: Carglumic Acid

  • Propionic_Acidemia

    Patients with confirmed diagnosis of propionic acidemia, and treated with carglumic acid, at any dose

    Drug: Carglumic Acid

Interventions

  • Maintenance therapy with carglumic acid

    Also known as: Carbaglu

06

What researchers measure

Primary outcomes

  1. Change in Number and Duration of Decompensation Events

    Change in the number of decompensation events before and after treatment with carglumic acid

    Time frame: 54 months

Secondary outcomes

  1. 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.

    Time frame: 18 months

  2. Caregiver Burden Exposure Frequency and Duration

    description of the patient and caregiver burden associated with MMA and PA

    Time frame: 18 months

  3. Caregiver Satisfaction Level

    Describe the MMA and PA patient and caregiver satisfaction with MMA or PA treatment

    Time frame: 18 months

  4. Maintenance Dosage of NCG

    Document the dosages of NCG used in maintenance treatment

    Time frame: 54 months

07

Study locations

31 of 32 sites recruiting
08

References and documents

Publications

  • 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. PubMed 35916811 ↗
  • 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. PubMed 34635114 ↗
  • 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. PubMed 32231837 ↗
  • 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. PubMed 33552909 ↗
  • 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. PubMed 29679984 ↗
  • 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. PubMed 27489777 ↗
  • 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. PubMed 38198106 ↗

Individual participant data

Plan to share: No

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Jan 2019 (actual). Primary completion is estimated for Dec 2024, 71 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 20, 2019
First posted
Nov 25, 2019
StartActual
Jan 15, 2019
Primary completionEst.
Dec 30, 2024
CompletionEst.
Jul 30, 2029
Last update
Feb 5, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Feb 5, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04176523
Responsible party
Sponsor
First posted
Nov 25, 2019
Start date
Jan 15, 2019
Primary completion
Dec 30, 2024 (estimated)
Completion
Jul 30, 2029 (estimated)
Last update
Feb 5, 2024

Study contacts

Vincenzo Giordano, MD
Contact
giordano.v@recordati.com
33 1 79911282
Sufin Yap, MD
principal investigator · Sheffield Children's NHS Trust

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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