An Efficacy and Safety Study of Ravulizumab in ALS Patients

Phase 1

• Conditions: Amyotrophic Lateral Sclerosis (ALS), motor neuron disease; MedDRA version: 21.1Level: PTClassification code 10002026Term: Amyotrophic lateral sclerosisSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

• Registration Number: EUCTR2019-004619-30-GB
• Lead Sponsor: Alexion Pharmaceuticals

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-02-07
• Last Update Posted: 30 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 354

Inclusion Criteria

1. 18 years of age or older, at the time of signing the informed consent.
2. A diagnosis of ALS, defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the revised World Federation of Neurology El Escorial criteria. Patients diagnosed with either sporadic or familial ALS are eligible for enrollment.
3. ALS onset, defined as time of onset of first muscle weakness (eg, limb weakness, dysarthria, dysphagia, shortness of breath), = 36 months from the Screening Visit.
4. Prestudy ALSFRS-R progression between disease onset and screening of -0.3 points per month or worse (calculated by ALSFRS-R total score decline from 48 divided by the months since onset of ALS symptoms).
5. Upright SVC = 65% predicted at Screening.
6. Vaccinated against N. meningitidis within 3 years prior to, or at the time of, initiating ravulizumab. Patients who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive appropriate prophylactic antibiotics until 2 weeks after the vaccination.
7. Patients who enter the trial receiving standard of care for ALS (ie, riluzole and/or edaravone), either in combination or monotherapy, must be on a stable dosing regimen of adequate duration prior to screening with no plan to discontinue or to change the dose during the study period as follows:
-If a patient who enters the study is receiving riluzole, the patient must have been on a stable dose of riluzole for = 30 days prior to Day 1.
-If a patient who enters the study is receiving edaravone, the patient must have initiated edaravone = 60 days (2 treatment cycles) prior to Day 1.
Note: Patients who are naïve to ALS therapies or have not taken approved ALS therapies for at least 30 days before screening are allowed to enroll.
8. Body weight = 40 kg at Screening.
9. Male and/or female
-Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
10. Capable of giving written or verbal informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 284
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion Criteria

1. History of N. meningitidis infection.
2. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer).
3. History of unexplained infections.
4. Active systemic bacterial, viral, or fungal infection within 14 days prior to study drug administration on Day 1.
5. Presence of fever = 38°C (100.4°F) within 7 days prior to study drug administration on Day 1.
6. Hypersensitivity to murine proteins or to 1 of the excipients of ravulizumab.
7. Dependence on invasive or non-invasive mechanical ventilation. Dependence on mechanical ventilation is defined as being unable to lie flat (supine) without it, unable to sleep without it, or daytime use > 6 hours per day for > 3 days per week. Non-invasive ventilation for sleep apnea is allowed subject to discussion with Medical Monitor.
8. Any medical condition that, in the opinion of the Investigator, might interfere with the patient’s participation in the trial, poses any added risk for the patient, or confounds the assessment of the patient.
9. The presence of unstable psychiatric disease or dementia that might interfere with the patient’s participation in the trial, poses any added risk for the patient, or confounds the assessment of the patient.
10. History of drug and/or alcohol abuse (according to Diagnostic and Statistical Manual of Mental Disorders) within 1 year of screening that would limit patient participation in the study as determined by the Investigator.
11. History of Parkinson’s disease, myasthenia gravis, multiple sclerosis, or any other neurological disorder that may confound the diagnosis or assessment of the patient as determined by the Investigator.
12. Previously or currently treated with a complement inhibitor.
13. Use of IV immunoglobulin (IVIg) within 3 weeks prior to screening.
14. Has a diaphragm pacing system (DPS) at study entry or anticipate DPS placement during the course of the study.
15. Participation in any other investigational product study or exposure to an investigational drug or device within 30 days of screening or 5 half-lives of the study drug, whichever is greater or any prior exposure to gene therapy.
16. Receipt of stem cell transplant therapy as an investigational treatment for ALS < 90 days from the date of last transplant.
17. Pregnant, breastfeeding, or intending to conceive during the course of the study.

Study & Design

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