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

AL-S Pharma

Status and phase: Completed; Phase 2

Conditions: Amyotrophic Lateral Sclerosis

Treatments: Drug: Placebo; Drug: AP-101

Study type: Interventional

Funder types: Industry

Identifiers

NCT05039099

2020-005971-11 (EudraCT Number)

AP101-02

Details and patient eligibility

About

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

Enrollment: 73 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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73 participants in 2 patient groups, including a placebo group

AP-101

Experimental group

Description:

AP-101 is administered by IV.

Treatment:

Drug: AP-101

Placebo

Placebo Comparator group

Description:

Placebo is administered by IV.

Treatment:

Drug: Placebo