Clinical trial NCT05039099: A Study to Evaluate, Safety, Tolerability, Pharmacodynamic (PD) Markers and Pharmacokinetics (PK) of AP-101 in Participants With Amyotrophic Lateral Sclerosis (ALS)
Official title: A Phase 2a, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety, Tolerability, Pharmacodynamic Markers, and Pharmacokinetics of AP-101 in Patients With Familial Amyotrophic Lateral Sclerosis (fALS) and Sporadic Amyotrophic Lateral Sclerosis (sALS)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Familial Amyotrophic Lateral Sclerosis
Sporadic Amyotrophic Lateral Sclerosis
Lead sponsor: AL-S Pharma
Sponsor class: INDUSTRY
First posted: 2021-09-09
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, PK, and PD of AP-101 in participants with fALS and sALS.


Eligibility criteria: Inclusion Criteria:

* All participants must adhere to contraception restrictions
* Female participants of childbearing potential must adhere to contraception restrictions
* Have possible, clinically probable, clinically probable-laboratory supported or definite familial or sporadic ALS in accordance with the El-Escorial criteria or who have a diagnosis of ALS as defined by the Gold Coast Criteria; progressive motor impairment documented by history or repeated clinical examination, preceded by normal motor development, and presence of upper and lower motor neuron dysfunction in at least 1 body region or lower motor neuron dysfunction in at least 2 body regions and investigations excluding other conditions
* In familial ALS participants, a confirmed pathogenic superoxide dismutase 1 (SOD1) mutation
* Onset of symptoms (i.e, weakness) within past 24 months prior to screening, at the time of obtaining informed consent
* Have slow vital capacity (SVC) of greater than or equal to (\> or =) 50 percentage (%) of predicted values. Participants with SVC of \<50% of predicted values may be permitted to enter the open-label extension, based on the opinion of the investigator
* Absence of bilevel positive airway pressure (BiPAP)/proportional assist ventilation (PAV) \> 4 hours for symptoms attributable to ALS. Use of a CPAP for pre-existing conditions will be allowed
* If on riluzole, must be on a stable dose.
* If on edaravone, must have completed 2 cycles and are expected to remain on the same dose throughout the study
* Able to provide informed consent which includes compliance with the requirements and restrictions
* Have venous access sufficient to allow for blood sampling
* Have clinical laboratory test results within the normal reference range for the population or study site, or results with acceptable deviations that are judged to be not clinically significant by the investigator

Exclusion Criteria:

* Have participated or currently participating in another clinical trial within 12 weeks of baseline (Day 1)
* Have undergone a tracheostomy for ALS symptoms
* Are on nasal intermittent positive pressure ventilation (NIPPV) \>4 hours per day for the treatment of ALS related symptoms
* Have other causes of neuromuscular weakness
* Have cognitive impairment, severe disease in the cardiovascular, hematological, renal system, neurodegenerative disease, pulmonary disorder, or psychiatric illness
* Pregnant or nursing women
* Have been exposed to any antisense treatment targeting SOD1 within 6 months of the baseline visit
* Have undergone stem cell therapy

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
timeFrame: From start of the study up to Week 51
measure: Number of Participants with Abnormalities in Vital Signs, Clinical Laboratory Assessments, Physical and Neurological Examinations, Electrocardiograms (ECGs)
timeFrame: From start of the study up to Week 51
Secondary outcomes:
measure: Elimination half-life (t1/2) of AP-101 in Serum
timeFrame: Predose up to Week 51
measure: Area Under the Drug Concentration-Time Curve (AUC)
timeFrame: Predose up to Week 51
measure: Concentration at End of Infusion (Cat EOI)
timeFrame: Week 24
measure: Change From Baseline in AP-101 Levels in the Cerebrospinal Fluid (CSF) up to Week 24
timeFrame: Baseline, up to Week 24
measure: Change From Baseline in Neurofilament Light Chain and Phospho-Neurofilament Heavy Chain Levels in the Cerebrospinal Fluid (CSF) up to Week 51
timeFrame: Baseline, up to Week 51
measure: Change From Baseline in Neurofilament Light Chain and Phospho-Neurofilament Heavy Chain Levels in Plasma up to Week 51
timeFrame: Baseline, up to Week 51
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego, ACTRI
state: California
city: Leuven
country: Belgium
facility: Department of Neurology, University Hospitals
city: Edmonton
country: Canada
facility: ALS clinic at the Kaye Edmonton Clinic, University of Alberta
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre - Victoria Hospital
state: Ontario
city: Toronto
country: Canada
facility: ALS Research Sunnybrook Health Sciences Centre
state: Ontario
city: Montréal
country: Canada
facility: Montreal Neurological Institute and Hospital / Dr Genge
state: Quebec
city: Berlin
country: Germany
facility: Charité
city: Bonn
country: Germany
facility: Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)
city: Hanover
country: Germany
facility: Hannover Medical School
city: Ulm
country: Germany
facility: Ulm University Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Medical Center
city: Stockholm
country: Sweden
facility: Studieenheten Akademiskt specialistcentrum, SLSO
city: Umeå
country: Sweden
facility: Norrlands universitetssjukhus/ University Hospital of Northern Sweden (NUS)
Study officials:
affiliation: AL-S Pharma SA
name: Study Director
role: STUDY_DIRECTOR
References: