A Study to Evaluate, Safety, Tolerability, Pharmacodynamic (PD) Markers and Pharmacokinetics (PK) of AP-101 in Participants With Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05039099
• Other study ID #: AP101-02
• Secondary ID: 2020-005971-11
• Status: Recruiting
• Phase: Phase 2
• Start date: September 2, 2021
• Est. completion date: January 18, 2025

Study information

• Verified date: August 2023
• Source: AL-S Pharma
• Contact: Study Director: AL-S Pharma SA
• Phone: 3176517036
• Email: choruspharma[@]lists.lilly.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 63
• Est. completion date: January 18, 2025
• Est. primary completion date: June 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• AP-101
Participants receive AP-101 by intravenous infusion (IV).
• Placebo
Participants receive placebo by IV.

Locations

Country	Name	City	State
Belgium	Department of Neurology, University Hospitals	Leuven
Canada	ALS clinic at the Kaye Edmonton Clinic, University of Alberta	Edmonton	Alberta
Canada	London Health Sciences Centre - Victoria Hospital	London	Ontario
Canada	Montreal Neurological Institute and Hospital / Dr Genge	Montréal	Quebec
Canada	ALS Research Sunnybrook Health Sciences Centre	Toronto	Ontario
Germany	Charité	Berlin
Germany	Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)	Bonn
Germany	Hannover Medical School	Hanover
Germany	Ulm University Hospital	Ulm
Korea, Republic of	Hanyang University Medical Center	Seoul
Sweden	Studieenheten Akademiskt specialistcentrum, SLSO	Stockholm
Sweden	Norrlands universitetssjukhus/ University Hospital of Northern Sweden (NUS)	Umeå
United States	UC San Diego, ACTRI	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
AL-S Pharma

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Germany,  Korea, Republic of,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, other situations.	From start of the study up to Week 51
Primary	Number of Participants with Abnormalities in Vital Signs, Clinical Laboratory Assessments, Physical and Neurological Examinations, Electrocardiograms (ECGs)		From start of the study up to Week 51
Secondary	Elimination half-life (t1/2) of AP-101 in Serum		Predose up to Week 51
Secondary	Area Under the Drug Concentration-Time Curve (AUC)		Predose up to Week 51
Secondary	Concentration at End of Infusion (Cat EOI)		Week 24
Secondary	Change From Baseline in AP-101 Levels in the Cerebrospinal Fluid (CSF) up to Week 24		Baseline, up to Week 24
Secondary	Change From Baseline in Neurofilament Light Chain and Phospho-Neurofilament Heavy Chain Levels in the Cerebrospinal Fluid (CSF) up to Week 51		Baseline, up to Week 51
Secondary	Change From Baseline in Neurofilament Light Chain and Phospho-Neurofilament Heavy Chain Levels in Plasma up to Week 51		Baseline, up to Week 51