Etheral Study - Protocol Version 2

• Research type

  Research Study

• Full title

  A multicentre, multinational, randomised, double-blind, placebo-controlled, 3-arm, 24-week parallel-group study to evaluate the safety, tolerability and preliminary efficacy of ORY-2001 in patients with mild-moderate Alzheimer's Disease. ETHERAL Study

• IRAS ID

  243516

• Contact name

  Emer MacSweeney

• Contact email

  EMacsweeney@re-cognitionhealth.com

• Sponsor organisation

  Oryzon Genomics S.A.

• Eudract number

  2017-004893-32

• Duration of Study in the UK

  1 years, 6 months, 1 days

• Research summary

  Research Summary
  Alzheimer’s disease (AD) is a severe neurodegenerative disorder that accounts for approximately 60-70% of all cases of dementia. It causes the progressive deterioration of cognitive function as well as other symptoms such as behavioural changes and physical wasting. Current treatments acetylcholinesterase inhibitors are only minimally effective at alleviating symptoms and have no impact on disease progression. The sponsor of this study, Oryzon Genomics S.A. has developed a drug called ORY-2001 for the treatment of Alzheimer's. ORY-2001 specifically inhibits proteins that are detrimental to mental ability, decreasing damage to neurons and improving their functioning. In addition to demonstrating that it is a safe drug, the ORY-2001 studies in animals indicate that ORY-2001 could be an option for the treatment of Alzheimer's. In humans, a study with healthy people demonstrated that ORY-2001 is safe and well-tolerated. The objective of this study is to find out whether it is also safe and well-tolerated in people with mild-to-moderate Alzheimer's. A further objective of this study is to find out whether ORY-2001 has an effect on neuropsychiatric symptoms, such as agitation, apathy, depression and cognitive impairment. Throughout the study participants will be allowed to continue on their medication (acetylcholinesterase inhibitors) for the treatment of Alzheimer´s.
  The study is divided into a screening, (three weeks) to see if the participants are eligible to enter the study, main (24 weeks) and extension (24 weeks) phase.
  The main and extension phase is blinded (neither participant nor doctor will know what treatment arm they are on). They will be randomly assigned (assigned by chance – like the flip of a coin) to one of the following treatments:
  Main - ORY-2001 0.6 mg, ORY-2001 1.2 mg or placebo (medicinal product that does not contain ORY-2001 and therefore does not have any effect). There is an 80% chance of receiving ORY-2001 and a 20% chance of receiving placebo.
  Extension - ORY-2001 0.6 mg, ORY-2001 1.2 mg
  The study medication will be taken as one capsule per day for 5 consecutive days, followed by 2 days of rest (without treatment) each week.
  Throughout the study participants will be asked to complete questionnaires as will their caregiver/relative. The participants will also have physical exams, blood pressure, heart rate, respiratory, weight, height and blood tests to see how their body is reacting to the study drug and to look for biomarkers. A Cerebrospinal fluid (CSF) sample will be taken to look for biomarkers, it will be taken by a lumbar puncture; this is where a needle is inserted into the lower part of the spine in order to extract the cerebrospinal fluid. An Electrocardiogram (ECG) will be taken to look at heart’s rate, rhythm and electrical activity. To look on the effect it has on the brain an MRI (magnetic resonance imaging) scan will be done. An MRI uses strong magnetic fields and radio waves to produce detailed images of the inside of the body. This will be at the beginning of this phase in week 1 and at week 24 for both main and extension phases. At the end of the study (30 days post last dose of drug) a safety visit will be done to see if there have been any changes to the participant’s health since they stopped study medication.
  This study will be conducted in several hospitals in three countries: Spain, the United Kingdom and France. It is hoped that out of 120 people screened that a total of 90 with Alzheimer’s will be recruited and go on the treatment phase of the study.

  Summary of Results
  A multicentre, multinational, randomised, double-blind, placebo-controlled, 3-arm, 24-week parallel-group study to evaluate the safety, tolerability and preliminary efficacy of ORY-2001 in patients with mild-moderate Alzheimer's Disease. ETHERAL Study.
  The study was conducted in 17 centers of 3 countries (France, Spain and UK).
  Please follow url links: https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agba4yu73OCS9U-2BkKS40W1kfZLMhYNSL6uAQ3D-2BHysQkrDeeFjdaBVDyLloOA5h3Y1fxYeVIjNgAYKaomhf-2Fp1TQOMPfmyQ-2BjCmN2s0Z-2FoWST7OnK5MckoW3u-2FTVIR7Q5J-2B1-2F2K4kSBEhRwvUcEXx93katKZvUuT6YfY8DoaYP6PdOqCuy_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YLp5yYcXaAbGm5OamSFnP-2BWPD27sELYopoLlQaXmf6fLL7aLtXG9BS-2BhKbRuEDlMOj9nKt0z1Avg3Z2-2FJgzsgYXEN3k6z5fB4OGhplmJ16I6UX68xGp-2BoYcM4Lp-2FXq-2F5MuIP0-2FVJTJ8vd-2B7RW6ea9n86fuQxPunDM7pB67tmcoqAA-3D-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C5581b7b961ba4bd3ad6308da11811b20%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637841543440974837%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=PSOzBPNaB5mhIQ4eqM68N2HPMiruNKBpEMocgASLbbI%3D&reserved=0
  https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agba4yu73OCS9U-2BkKS40W1kfatiYvtk1-2B2gi1K6vKImual9G6VG4-2FeFhNKGHEnJKTVStrjUUEvU8-2FksUb3JylZQzWgiiJjfc2vzpR2TnLJmhsFSU3E_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YLp5yYcXaAbGm5OamSFnP-2BW14FeTSXZ2-2F4HsfDdHK8gRPdFL-2BR3c4EXV71Y9jTi888LuC-2FMrIFs-2BGjamo1ms6eH1UKdxW450megnD1glJcdRXnGiZMOPahgi6-2FOnGRmGoyP7kWh4BWtQTcaXZeUorg2AlYpP47-2BFOUQOQ-2FIcP6HdA-3D-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C5581b7b961ba4bd3ad6308da11811b20%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637841543440974837%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=Qy%2B5FZBVS9qxZQdxhHWLgOPUx%2FV%2BiLhKyTe0TN%2B3hyU%3D&reserved=0

• REC name

  East Midlands - Leicester South Research Ethics Committee

• REC reference

  18/EM/0093

• Date of REC Opinion

  9 May 2018

• REC opinion

  Further Information Favourable Opinion