NH00004 IONIS Chart Review FUS-ALS

• Research type

  Research Study

• Full title

  A Retrospective Chart Review Study of the Natural History and Disease Progression in Amyotrophic Lateral Sclerosis Patients with Fused in Sarcoma Mutations (FUS-ALS)

• IRAS ID

  334139

• Sponsor organisation

  Ionis Pharmaceuticals, Inc.

• Duration of Study in the UK

  1 years, 0 months, 31 days

• Research summary

  This is a Retrospective, observational, study that will collect pseudonymised patient data from existing medical records of patients with Amyotrophic Lateral Sclerosis with Fused in Sarcoma Mutations (FUS-ALS) and record in the study eCRF.
  FUS-ALS is a rare disease, and its exact prevalence is not known. The natural history, particularly with regards to the variability of disease progression, remains largely uncharacterized. The unmet need in this disease is high as there are no available disease-modifying treatments.
  Published reports on FUS-ALS include retrospective chart reviews with a very limited number of patients and variable periods of follow-up. Therefore, there is a lack of real-world data describing the longitudinal evolution of FUS-ALS clinical characteristics, and patterns and variability of disease progression.
  Medical records or registry data from approximately 100-150 patients are planned to be included in this study, selected from multiple sites worldwide.
  The data will be collected from the retrospective time period from 01 Jan 2000 to End-of-Study Period (currently projected for 22 Dec 2023) only and no current or prospective data collection will occur. Eligible patients may be deceased or still alive at time of study start.
  For each participant, data will be extracted back since the first record of a sign or symptom suggestive of ALS disease process onset until the earliest of death or death equivalent, last chart record, or end of study observation period. In addition, medical, developmental, educational, and treatment history before onset will also be ascertained. The study will end when the data of the last participant are fully extracted. No direct participant identifiers (e.g., participant name, initials, institutional identification numbers, medical record number, complete date of birth, etc.) will be collected.
  The data collected in this retrospective natural history study will be critical in supporting future clinical trials to address the unmet need in this rare disease.

  Lay summary of study results: A Study to Understand the History and Worsening of Amyotrophic Lateral Sclerosis in People with Fused in Sarcoma Gene Changes

  Protocol #: NH00004

  Study dates: April 2023 to November 2024

  Thank you to the participants who took part in the study “A Retrospective Chart Review Study of the Natural History and Disease Progression in Amyotrophic Lateral Sclerosis Patients with Fused in Sarcoma Mutations (FUS-ALS)”.

  This study helped researchers learn how amyotrophic lateral sclerosis (ALS) linked to the fused in sarcoma (FUS) gene develops and changes over time.

  Why was this study done?

  ALS is a disease that damages nerve cells in the brain and spinal cord. These nerve cells control muscle movement. Damage to them causes weakness in muscles that may make it difficult to walk, talk, eat, and breathe. It is a progressive disease, which means that it slowly gets worse with time.

  ALS with changes in the FUS gene is a very rare form of the disease. Since it is rare, doctors and researchers are still learning how often it occurs and how the disease changes over time. There are currently no treatments available that directly target the FUS gene in order to slow or stop the worsening of FUS-ALS.

  In this study, researchers wanted to collect more information on FUS-ALS. To do this, they reviewed patients’ medical records to better understand how the disease develops from before diagnosis through later stages over time. This information can help researchers develop new treatments and support future research.

  When was this study done?

  This study started in April 2023 and ended in November 2024.

  Who took part in this study?

  Participants could take part if they:
  • Had initial signs of ALS, or were diagnosed with ALS, on or after 1 January 2000.
  • Had medical records or registry data available that researchers could review.

  Participants could not take part if their medical records or registry data did not include all of the following:

  • The age when their first ALS signs or symptoms appeared.
  • The part of the body where the first ALS signs or symptoms started.
  • The age when they had a confirmed diagnosis of ALS.
  • Confirmation of a FUS gene change through genetic testing.

  How many people took part in this study?

  A total of 147 participants took part in this study. Of these, 118 participants had a change in the FUS gene that would have qualified them for a study of a possible treatment for FUS-ALS (Study ION363-CS1). These 118 participants were included in the main analysis.

  Out of the 118 participants, 59 were men (50%) and 59 were women (50%).

  The study took place at 13 clinical sites in Belgium, Germany, Ireland, Italy, the Netherlands, Poland, South Korea, Spain, the United Kingdom, and the United States.

  What happened during the study?

  What did researchers want to know?

  Researchers wanted to know how FUS-ALS developed over time, starting before diagnosis and continuing through the course of the illness.

  The main questions researchers wanted to answer were:

  • How long did participants live after their first ALS signs or symptoms began?
  • How did participants’ physical function change over time?

  What treatments were studied?

  • No treatments were administered in this observational study. Researchers collected information from the participants’ medical records that showed how FUS-ALS developed over time.

  How was the study done?

  There are many types of clinical studies. This study was:

  • Retrospective: Researchers collected information from the medical records of participants who took part in the study.
  • Observational: Researchers collected information about people without giving them a new treatment or changing their routine care.

  Study Periods

  Inclusion Period

  • The study included people who showed initial ALS signs or symptoms or were diagnosed with ALS between 1 January 2000 and the end of the study.
  • Only people with medical records or registry data that met the study requirements could take part.

  Observation Period

  • For each participant, information was collected from the time their first ALS signs or symptoms appeared.
  • Data collection continued until participant death, loss to follow-up, or the end of the study.

  Patient data collection periods

  Researchers looked at the following time points for each participant:

  • Clinical onset of ALS: the date when the first ALS sign, symptom, or laboratory test result was recorded.
  • Confirmed ALS diagnosis: the date when the ALS diagnosis was confirmed.
  • End of follow-up: the date when the participant was last documented in medical records, along with the reason the study ended for them (such as death, loss to follow-up, or end of study).

  Researchers collected the following data from the participants’ medical records:

  • Basic background details: age, sex, country, ethnicity, and family history of ALS.
  • Genetic information: confirmation of changes in the FUS gene and any other relevant genetic findings.
  • ALS details: when the first symptoms began, where in the body they appeared, and when was it confirmed.
  • Health and medical history: important medical events, treatments, and results from medical tests (such as imaging scans, blood tests, lung function).
  • Impact of ALS over time: changes in speech, movement, eating, breathing, and ability to carry out daily activities.
  • Support requirement: use of breathing support or feeding tubes.
  • Final status: whether the participant was alive, using permanent breathing support, had passed away, or could not be followed up at the end of the study period.

  What were the results?

  How long did participants live after their first ALS symptoms began?

  Researchers wanted to understand how long participants lived after they had their first ALS sign or symptom.

  Researchers found that:

  • 74 out of 118 (63%) participants had a known date of death in their records.
  • On average, they had lived for about 2 years and 8 months (32 months) after their first ALS sign or symptom.

  How did participants’ physical function change over time?

  Researchers looked at changes in participants’ daily function over time. They did this by recording scores from a tool called the ALS Functional Rating Scale–Revised (ALSFRS-R). This scale measures how well people could do everyday activities such as speaking, swallowing, and moving. A lower score means the person is having more difficulty with daily activities, and their symptoms are getting worse.

  Researchers found that:

  • 77 out of 118 (65%) participants had at least one ALSFRS-R score recorded.
  • On average, their ALSFRS-R scores went down by about 1.2 points each month (around 14.5 points each year).
  

• REC name

  Yorkshire & The Humber - Leeds West Research Ethics Committee

• REC reference

  23/YH/0283

• Date of REC Opinion

  17 Jan 2024

• REC opinion

  Further Information Favourable Opinion