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

NCT05039099 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: AP101-022020-005971-11
• Study Type: interventional
• Target: 73
• Locations: 6 countries
• Sites: 13

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Familial Amyotrophic Lateral Sclerosis; Sporadic Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (6)

• Elimination half-life (t1/2) of AP-101 in Serum

  Predose up to Week 51

• Area Under the Drug Concentration-Time Curve (AUC)

  Predose up to Week 51

• Concentration at End of Infusion (Cat EOI)

  Week 24

• Change From Baseline in AP-101 Levels in the Cerebrospinal Fluid (CSF) up to Week 24

  Baseline, up to Week 24

• 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

Study Arms (2)

AP-101

EXPERIMENTAL

AP-101 is administered by IV.

Drug: AP-101

Placebo

PLACEBO COMPARATOR

Placebo is administered by IV.

Drug: Placebo

Interventions

AP-101 DRUG

Participants receive AP-101 by intravenous infusion (IV).

AP-101

Placebo DRUG

Participants receive placebo by IV.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AL-S Pharma: lead

Study Sites (13)

UC San Diego, ACTRI

La Jolla, California, 92037, United States

Location

Department of Neurology, University Hospitals

Leuven, 3000, Belgium

Location

ALS clinic at the Kaye Edmonton Clinic, University of Alberta

Edmonton, Alberta, AB T6G 1Z1, Canada

Location

London Health Sciences Centre - Victoria Hospital

London, Ontario, ON N6A 5W9, Canada

Location

ALS Research Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Montreal Neurological Institute and Hospital / Dr Genge

Montreal, Quebec, H3A 2B4, Canada

Location

Hannover Medical School

Hanover, Hanover, 30625, Germany

Location

Charité

Berlin, State of Berlin, 13353, Germany

Location

Ulm University Hospital

Ulm, Ulm, 89081, Germany

Location

Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)

Bonn, 53127, Germany

Location

Hanyang University Medical Center

Seoul, Seoul, 04763, South Korea

Location

Studieenheten Akademiskt specialistcentrum, SLSO

Stockholm, Stockholm County, 113 61, Sweden

Location

Norrlands universitetssjukhus/ University Hospital of Northern Sweden (NUS)

Umeå, SE- 901 85, Sweden

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Amyotrophic lateral sclerosis 1

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Study Director

  AL-S Pharma SA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: September 9, 2021
• Study Start: September 2, 2021
• Primary Completion: August 13, 2025
• Study Completion: August 13, 2025
• Last Updated: August 19, 2025

Record last verified: 2025-08

Locations

DE (4); SE (2); US (1); BE (1); CA (4); KR (1)