An Efficacy and Safety Study of Ravulizumab in ALS Patients

• Register: EUCTR
• Last refreshed on: 2 March 2022
• Main ID: EUCTR2019-004619-30-IE
• Date of registration: 03/02/2020
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals
• Public title: An Efficacy and Safety Study of Ravulizumab in ALS Patients
• Scientific title: A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Multicenter Study With an Open-Label Extension to Evaluate the Efficacy and Safety of Ravulizumab in Patients With Amyotrophic Lateral Sclerosis (ALS) - An Efficacy and Safety Study of Ravulizumab in ALS Patients
• Date of first enrolment: 14/09/2020
• Target sample size: 354
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-004619-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Open Label Extension; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, Denmark, France, Germany, Ireland, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: European Clinical Trial Information
• Affiliation: Alexion Europe SAS

• Name: European Clinical Trial Information
• Affiliation: Alexion Europe SAS

Key inclusion & exclusion criteria

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:
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

Amyotrophic Lateral Sclerosis (ALS), motor neuron disease
MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: Ultomiris
Product Name: ravulizumab
Product Code: ALXN1210
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RAVULIZUMAB
CAS Number: 1803171-55-2
Current Sponsor code: ALXN1210
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): Change from baseline in ALSFRS-R total score

Timepoint(s) of evaluation of this end point: Week 50 visit

Secondary Objective: To evaluate the effect of ravulizumab compared with
placebo on ventilation assistance-free survival (VAFS) in
adult patients with ALS

To evaluate the effect of ravulizumab compared with
placebo on respiratory function in adult patients with
ALS

To evaluate the safety of ravulizumab compared with
placebo in adult patients with ALS

To evaluate the effect of ravulizumab compared with
placebo on muscle strength in adult patients with ALS

To evaluate the effect of ravulizumab compared with
placebo on neurofilament light chain (NfL)
concentrations in adult patients with ALS

To characterize the pharmacokinetics (PK) of
ravulizumab in adult patients with ALS

To characterize the pharmacodynamics (PD) of
ravulizumab in adult patients with ALS

To characterize the immunogenicity of ravulizumab in
adult patients with ALS

Main Objective: To evaluate the effect of ravulizumab compared with
placebo on amyotrophic lateral sclerosis functional rating
scale-revised (ALSFRS-R) score in adult patients with
amyotrophic lateral sclerosis (ALS)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 50; throughout the study

Secondary end point(s): Time to the earliest occurrence of 1 of the following events during the 50-week Randomized Controlled Period:
• All-cause mortality
• First use of non-invasive ventilation (NIV) for
= 22 hours per day for = 10 consecutive days
• First use of permanent assisted ventilation (PAV) for
= 22 hours per day for = 7 consecutive days
• Change from baseline in percent (%) predicted slow vital capacity (SVC) at Week 50
• Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and TEAEs leading to study drug discontinuation
• Percent change in combined muscle megascore from baseline at Week 50 as assessed by handheld dynamometry (HHD)
• Change from baseline in NfL concentrations in serum at Week 50
• Change in serum ravulizumab concentration over the study duration
• Change in serum free complement component 5 (C5) concentration over the study duration
• Presence and titer of antidrug antibodies (ADAs)

Secondary ID(s)

ALXN1210-ALS-308

145660

NCT04248465

Source(s) of Monetary Support

Alexion Pharmaceuticals

Ethics review

Status: Approved
Approval date: 14/09/2020
Contact: