ADORE

A multicentre, randomised, double-blind, placebo-controlled study to investigate the efficacy and safety of FAB122 in patients with Amyotrophic Lateral Sclerosis

ADORE (ALS Deceleration with ORal Edaravone) study

UK Chief Investigator

Professor Chris McDermott

Research summary

Amyotrophic Lateral Sclerosis (ALS) is a very serious and fatal condition clinically characterized by muscle weakness and functional decline. This study is to assess the effect of treatment with 100 mg of FAB122 (edaravone) on disease progression in ALS patients.

It concerns a multicenter, multinational, double-blind, randomized (2:1), placebo-controlled Phase III study. Approximately 300 subjects will be recruited by hospital sites located in the EU (26 sites), UK (4 sites) and Russia (1 site).

Subjects will visit the clinic at Screening, Baseline, Week 4, Week 12, and every 12 weeks thereafter. Monthly telephone visits telephone visits are performed in between the visits to the clinic until Week 48.

Blood sampling for FAB122 plasma concentrations will be done in ~90 subjects treated with the study drug. The study will also evaluate the PK interaction between riluzole and FAB122.

After a subject completed the study (max at 72 weeks), he/she will be offered the possibility to roll over in an open label extension trial in which all subjects will be offered to receive FAB122.

Inclusion / exclusion criteria

Key inclusion criteria:

1. Age 18 – 80 years (both inclusive), male or female.

2. Diagnosis of definite, probable, probable laboratory supported or possible ALS as based on the El Escorial and the revised Airlie House diagnostic criteria for ALS.

3. Onset of first symptoms no longer than 24 months prior to randomisation.

4. SVC equal to or more than 70% of the predicted normal value for gender, height and age at screening visit.

5. Change in ALSFRS-R score between 0.35 points and 1.5 points per month (both inclusive) in the period from onset of first symptoms to the Screening visit.

6. A female subject should not be able to become pregnant (not of reproductive potential, or of reproductive potential and agreeing to true abstinence or practicing adequate birth control methods).

7. Capable of providing informed consent and complying with trial procedures.

Key exclusion criteria:

1. Diagnosis of Primary Lateral Sclerosis, Frontotemporal Dementia, other neurodegenerative diseases (e.g. Parkinson disease, Alzheimer disease) or polyneuropathy.

2. Other causes of neuromuscular weakness.

3. Have a significant pulmonary disorder not attributed to ALS and/or require treatment interfering with the evaluation of ALS on respiratory function.

4. Use of intravenous (IV) edaravone within 6 months of the screening visit.

5. Depend on mechanical ventilation (invasive or non-invasive) or require tracheostomy at Screening.

6. Renal impairment as indicated by a creatinine clearance of less than 50 mL/min as calculated by the Cockcroft Gault equation.

7. Subject has a history of clinically significant hepatic disease, hepatitis or biliary tract disease, or subject has a positive screening test for HIV, hepatitis B or C.

8. Presence of any of the following clinical conditions: a. Unstable cardiac, pulmonary, endocrine, hematologic or active infectious disease; b. Unstable psychiatric illness defined as psychosis, untreated major depression within 90 days of the screening visit; c. Significant cognitive impairment, clinical dementia or psychiatric illness; d. Cancer that is currently under active treatment or is likely to require treatment during the trial that may alter the subject's function and interfere with assessment of ALS disease progression.

9. Any comorbidity that may interfere with the functions as scored with the ALSFRS-R.

10. History of known sensitivity or intolerability to edaravone, to any related compound, or to any of the excipients.

11. Exposure to any investigational drug within 30 days of the screening visit.

12. Current substance or alcohol dependence.

Current status

Open to recruitment

Locations

  • Royal Hallamshire Hospital, Sheffield

  • John Radcliffe Hospital, Oxford

  • King's College Hospital, London

  • The Walton Centre, Liverpool Opening soon

Information about study sites

Contact details

Email: info@tricals.org

Recruitment group(s)

Patients with MND

Recruitment target(s)

Up to 300 participants globally (30 participants in the UK)

Key dates

Actual opening date: December 2021

Recruitment planned end date: 17 September 2022

Funder(s)

Ferrer Internacional SA

Sponsor

Ferrer Internacional SA

Study design

Interventional, randomised controlled trial

Intervention (if applicable)

  • Drug: Oral Edaravone (FAB122)

  • Placebo

Phase (if applicable)

3

Outcome measures

Primary outcome measure

  • Change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R)

Secondary outcome measures

  • To evaluate the effect of treatment with FAB122 on survival

  • To evaluate the safety and tolerability of FAB122

  • To evaluate the effect of treatment with FAB122 on quality of life (QoL)

  • To evaluate the effect of treatment with FAB122 on cognitive functioning

  • To evaluate the pharmacokinetics (PK) of FAB122

Publications / Results reports

Links will be provided when papers are published.