Investigate study drug Arimoclomol with patients diagnosed with NP-C
Research type
Research Study
Full title
Arimoclomol prospective double blind, randomised, placebo-controlled study in patients diagnosed with Niemann Pick disease type C
IRAS ID
199185
Contact name
Stephanie Grunewald
Contact email
Sponsor organisation
WORLDWIDE CLINICAL TRIALS
Eudract number
2015-004438-93
Duration of Study in the UK
1 years, 3 months, 0 days
Research summary
Summary of Research: Niemann-Pick type C disease (NPC) is an inherited, rare and neurodegenerative disease. Symptoms can include deterioration of memory and balance, lung and liver failure, delayed motor development, and seizures. The disease usually appears in early childhood, leading to neurological problems that are typically fatal. One in every 150,000 children has NPC. A specific treatment for NPC is not available, only supportive therapies are available.
The purpose of this study is to look at the effectiveness and safety of a new treatment for Niemann Pick disease type C (NPC). Arimoclomol will be compared to placebo, when it is given as an add-on therapy to the current prescribed treatment or to care patients receive for their underlying condition.
Approximately 46 patients will participate in this study, which will be taking place in 15 to 20 sites across Europe.
Summary of Results:
A clinical trial testing how arimoclomol works in children with Niemann-Pick disease type C who are more than 6 months old and less than 2 years oldAbout this summary
This summary is written to inform the public in plain language about the results of a clinical trial.
A clinical trial is research involving tests performed on people. Such research is designed to answer questions about diseases, treatments, or other factors that can affect our health. The results of a clinical trial are described in a detailed report for researchers, health professionals, and authorities who approve medicines. This is a short summary of that report. The results shown here are from a single trial. Many trials are needed to find out if a medicine works and is safe to use. Do not change your current medical treatment based on the results shown in this summary. Always consult your doctor.
If you would like to find more detailed information about this clinical trial, please see the websites mentioned in Section 10.1. General information about the trial
When and where did the trial take place?
The trial started in December 2018 and ended in October 2024. The trial took place in 4 countries (Denmark, Germany, United Kingdom and United States of America).Why is this trial important?
Niemann-Pick disease type C is a very rare genetic condition that affects many of the body’s organs and systems, including the central nervous system. The genetic variations lead to defective proteins which disrupt the body’s ability to transport cholesterol and other fatty substances (lipids) inside of cells. This leads to an abnormal buildup of these substances within several tissues of the body, including brain tissue. The buildup of these substances damages the affected areas.
Signs and symptoms of Niemann-Pick disease type C generally first appear in childhood, but can present at any time, including adolescence or adulthood. Because of the progressive nature of Niemann-Pick disease, signs and symptoms become more pronounced over time.
Symptoms may include:
• Enlarged liver and spleen
• Difficulty coordinating movement
• Abnormal eye movements
• Poor muscle tone
• Severe liver disease
• Frequent respiratory infections
• Difficulty with speech
• Difficulty with swallowing and feeding • Loss of cognitive skills • SeizuresBecause signs and symptoms may not appear early on, and because it takes time to confirm the disease, very young patients below 2 years of age are even more rarely seen. Most clinical trials are performed with older patients.
What did researchers want to find out?
The researchers wanted to know if arimoclomol was safe and well tolerated in children who were more than 6 months old and less than 2 years old at the start of the trial.
The researchers also wanted to check the development of these very young patients during the trial. This was done by a test called “Bayley III”.
To confirm that the patients received the correct dose of trial medicine, the trial also measured how much arimoclomol was found in the blood of the patients.
Type of trial
This was a substudy to a phase 2/3 trial. In phase 2 and 3 trials, researchers give a trial medicine to many people with a specific condition to learn how well the medicine works and how safe the medicine is.
This substudy was performed to ensure necessary data from very young children was collected to support the approval of arimoclomol treatment for children with Niemann-Pick disease type C.2. Who took part in this trial?
In this trial, 5 children took part: 3 girls and 2 boys.
To be in the trial, the children had to:
• have genetically confirmed Niemann-Pick disease type C • be 6 to <24 months old at the start of the trial • be on stable treatment with the medicine miglustat for at least 1 month, if they were treated with this medicine Children were not allowed to take part in this trial if:
• they had had a liver transplantation
• they had poor kidney function
• they had conditions that could cause liver disease or problems with other organs besides Niemann-Pick disease type C • the doctor did not think they were well enough to allow the blood collection that was required for the trial3. What treatments were studied?
The medicine studied in this trial was arimoclomol. Arimoclomol is a new medication for the treatment of Niemann–Pick disease type C. It is taken by mouth, either suspended in liquid or soft food, or taken as a capsule.
The patients were treated with arimoclomol for up to 36 months.
Arimoclomol was given 3 times per day according to the patient’s body weight.
Children under 2 years old were given 1.98 mg arimoclomol base/kg, 3 times per day.
If a patient turned 2 years old during the trial, arimoclomol was dosed according to weight-range:
• 8–15 kg: 31 mg 3 times per day (93 mg/day) • >15–22 kg: 47 mg 3 times per day (141 mg/day) • >22–38 kg: 62 mg 3 times per day (186 mg/day) • >38–55 kg: 93 mg 3 times per day (279 mg/day) • >55 kg: 124 mg 3 times per day (372 mg/day) This was an open-label trial. This means that both the researchers and the parents or parents substitute (legal authorized representative) of children in the trial knew which medicine and dose was being used.4. What were the overall results of the trial?
The results from this trial showed that arimoclomol was well tolerated and no safety concerns were identified for the group of patients who were more than 6 months old and less than 2 years old.
All 5 patients experienced adverse events (unwanted medical events) during the trial. Most of the adverse events in the trial were mild in nature.
Assessments of development during the trial (Bayley III), showed that among the 5 participating patients:
• 1 patient got better (gained skills),
• 2 patients were stable,
• 1 patient declined,
• And development could not be measured for the last patient.
The amount of arimoclomol found in blood tests confirmed that the patients had received the correct dose.
More details on this trial can be found on the websites in Section 10.5. What were the side effects?
Adverse event: an unwanted medical event. The doctors do no necessarily think that an adverse event is caused by the trial medicine.
Side effect: an unwanted medical event (adverse event) which the doctor believes may be cause by the trial medicine.What are side effects?
Side effects are unwanted medical ‘events’ which the doctor thinks could be caused by the medicine studied in the trial.
A side effect is serious if it:
• leads to death,
• is life-threatening,
• puts someone in the hospital or keeps them in the hospital for a longer time, • causes a birth defect, • causes a disability that lasts a long time or • needs medical or surgical treatment to prevent any of the above, as judged by the doctor.
What were the serious side effects?
None of the patients in this substudy experienced serious side effects.
What were the most common side effects?
Among the 5 patients, 1 patient experienced 2 side effects. The side effects were high levels of 2 kinds of liver enzymes (alanine aminotransferase and aspartate aminotransferase). The patient stopped taking trial medicine because of the side effects and the liver enzyme levels returned to normal.6. How has the trial helped patients and researchers?
This trial is just one of many trials. The trials are performed to find out how best to use arimoclomol to treat people with Niemann-Pick disease type C.
In this trial, researchers found that arimoclomol was safe to be used in children with Niemann-Pick disease type C who are more than 6 months old and less than 2 years old.
Findings from this trial will be used to further improve the optimal use of arimoclomol in children.
These results are for this trial only. Other trials may show different results.7. Are there plans for further trials?
At the time of this summary, no other trials testing arimoclomol for treatment of Niemann-Pick disease type C are ongoing.8. Trial name
Trial name: Arimoclomol prospective double-blind, randomized, placebo-controlled trial in patients diagnosed with Niemann-Pick disease type C – Pediatric substudy Phase of clinical development: Phase 2/3 EudraCT number: 2015-004438-93 National Clinical Trial number: NCT02612129 IND number: 1245479. Who sponsored the trial?
Trial sponsor: Zevra Denmark A/S
Contact details: Zevra Denmark A/S, Nordre Fasanvej 215, 2000 Frederiksberg, Denmark
E-mail: info@zevra.com
Internet: https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.zevra.com%2F&data=05%7C02%7Champshirea.rec%40hra.nhs.uk%7Cac937525dfb34d22ae6b08ddb5750d59%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638866236536666766%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=WumrhZc2%2FID2NSa3B0mOG5iT2XdBZQODMEVfna0GzOo%3D&reserved=010. Where can I find more information?
You can find more information about the trial or the trial treatment at these websites:
• EUs clinical trials register https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C02%7Champshirea.rec%40hra.nhs.uk%7Cac937525dfb34d22ae6b08ddb5750d59%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638866236536680103%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=NlyXDyGh8X%2Fp5nULxzNKYD2hCbxXgOZlIU%2FYI05umA0%3D&reserved=0, (for this trial: 2015-004438-93) • US government clinical trials website https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C02%7Champshirea.rec%40hra.nhs.uk%7Cac937525dfb34d22ae6b08ddb5750d59%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638866236536692892%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=f2PSb3ZpYbiOmly4EaA%2BmXMNh11vf9rnaar7lXIAXKA%3D&reserved=0, (for this trial: NCT02612129) For general information about clinical trials please go to:
• https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fzevra.com%252Fscience-pipeline%252F%2523clinical-trials%2FNBTI%2FRUy_AQ%2FAQ%2F5f401b29-15db-41ca-8232-3df210c12959%2F2%2F-zOXutVHH6%23clinical-trials&data=05%7C02%7Champshirea.rec%40hra.nhs.uk%7Cac937525dfb34d22ae6b08ddb5750d59%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638866236536705648%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=VtRK74PRfeLI0vxIut3V8MdmDgmfXqduvWH2pJaDYUY%3D&reserved=0REC name
South Central - Hampshire A Research Ethics Committee
REC reference
16/SC/0067
Date of REC Opinion
20 Feb 2016
REC opinion
Favourable Opinion