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)

AP-101 is a monoclonal antibody that binds to misfolded forms of SOD1, which are considered to be the most likely mechanism in ALS caused by SOD1 mutations, and which are also present in the CSF of sporadic ALS. The assumed mechanism of AP-101 is its specific binding to such misfolded SOD1 and its subsequent removal by phagocytosis, while not binding to the native form of SOD1 that is essential for human biological functions. AP-101 is administered by intravenous infusion.

In transgenic preclinical models, AP-101 generated highly significant therapeutic effects and the SAD study showed a very beneficial safety profile of AP-101 in humans at all dose levels tested.

In the absence of any disease-modifying treatment modality, we believe that the current AP-101 phase 2 study offers a valuable treatment option for ALS patients by its multiple dosing during 6 months with an additional 6 months open label extension.

The study is recruiting patients now, and further information on the active sites are available at clinicaltrials.gov identifier NCT05039099.

Michael Salzmann, CEO & Dr. Angela Genge, Global PI & Head of Clinical Advisory Board

Minimum Age:

18 Years

Maximum Age:

N/A

Can participants use Riluzole?

Yes

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