Clinical Study of Dexpramipexole in Amyotrophic Lateral Sclerosis (ALS)

Phase 1

• Conditions: Amyotrophic lateral sclerosis (ALS); MedDRA version: 14.1Level: PTClassification code 10002026Term: Amyotrophic lateral sclerosisSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2010-022818-19-BE
• Lead Sponsor: Biogen Idec Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01-24
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 915

Inclusion Criteria

1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
2. Subject is between 18 and 80 years of age (inclusive) on Day 1.
3. Subject is diagnosed with sporadic or familial ALS.
4. Subject had onset of first ALS symptoms =24 months prior to Day 1.
5. Subject meets the possible, laboratory-supported probable, probable, or definite criteria for diagnosing ALS according to the World Federation of Neurology El Escorial criteria (revised according to the Airlie House Conference 1998). Subjects meeting the definition of possible ALS” must have upper motor neuron (UMN) and lower motor neuron (LMN) signs/symptoms in at least 1 region).
6. Subject has an upright SVC =65% of predicted value for age, height, and gender at screening.
7. Subject has not taken riluzole for at least 30 days prior to Day 1, or has been on a stable dose of riluzole for at least 60 days prior to Day 1. (Riluzole-naïve subjects are permitted in the study.)
8. Subject is medically able to undergo the study procedures and to adhere to the visit schedule at the time of study entry.
9. Subject is able to take oral treatment without crushing or breaking the tablets at the time of study entry as assessed by the site Investigator.
10. Subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 1 month (females) or 3 months (males) after their last dose of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 915
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subject in whom causes of neuromuscular weakness other than ALS have not been excluded.
2. Subject with significant cognitive impairment, clinical dementia, or psychiatric illness
3. Subject with a diagnosis of other neurodegenerative diseases (e.g., Parkinson’s disease, Alzheimer’s disease, etc.)
4. Subject with a clinically significant history of unstable or severe cardiac, oncologic, hepatic, or renal disease, or other medically significant illness
5. Subject with a clinically significant pre-existing pulmonary disorder not attributed to ALS
6. Subject with a history of severe drug allergy or severe allergic disease (anaphylactic shock)
7. Subject with clinically significant ECG abnormalities at the Screening visit (e.g. QTc >500 msec (where QTc is the interval between the start of the QRS complex and the end of the T wave corrected for heart rate), or acute ST segment elevations)
8. Subject with clinically significant abnormal clinical laboratory values, as determined by the Investigator at the Screening visit
9. Subject with absolute neutrophil count (ANC) <1.96 x 1000/µL at the Screening visit or any documented history of neutropenia
10. Subject with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value >3.0 times the upper limit of normal at the Screening visit
11. Subject with creatinine clearance (CrCl, calculated according to the Modification of Diet in Renal Disease equation) =50 mL/minute at the Screening visit
12. Pregnant women or women breastfeeding
13. Subject with a history of alcohol or drug abuse within 1 year of Day 1, as determined by Investigator
14. Subject unlikely to comply with study requirements
15. Subject who has been exposed to any other experimental agent (off-label use or investigational) within 30 days of Day 1.
16. Subject with prior exposure to dexpramipexole
17. Subject taking pramipexole or other dopamine agonists

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to evaluate the efficacy of oral administration of dexpramipexole 150 mg twice daily compared to placebo for 12 months in subjects with amyotrophic lateral sclerosis.;Secondary Objective: The secondary objectives are to evaluate the safety and pharmacokinetic (PK) profiles of oral administration of 150 mg twice daily dexpramipexole.;Primary end point(s): The primary endpoint is a joint rank of functional outcomes adjusted for mortality. The joint rank analysis is based on change from baseline in ALSFRS-R score and time to death using follow-up data through 12 months.;Timepoint(s) of evaluation of this end point: ALSFRS-R is measured at screening, baseline and then monthly (+/- 7 days)