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 ALS (fALS) and sporadic ALS

Study Purpose:

Two participant cohorts will participate in this study: fALS patients with confirmed mutations in SOD1 and patients with sALS. Patients in each participant cohort will be randomly assigned in a 2:1 ratio to either AP‑101 treatment or to placebo. Patients will be allowed to continue on riluzole or edaravone per the inclusion/exclusion criteria for the duration of the study. Participants will receive a loading dose on Day 1, and then 3 weekly scheduled doses of 2500 mg will begin on Day 2. Participants will be on study medication up to 24 weeks, and on study up to 40 weeks. Following completion of 6 months of treatment, participants will be invited to join a 6-month open‑label extension (OLE) that will continue to evaluate long-term safety for AP-101.

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Enrolling

Phase:

Phase II

Study Chair(s)/Principal Investigator(s):

Dr Rami Massie, Montreal Neurological Institute and Hospital

Clinicaltrials.gov ID (11 digit #):

NCT05039099

Neals Affiliated?

No

Coordinating Center Contact Information

Montreal Neurological Institute and Hospital
Matthias Couillard / .(JavaScript must be enabled to view this email address)
.(JavaScript must be enabled to view this email address) Canada

Full Study Summary:

Study Sponsor:

AL-S Pharma, AG

Participant Duration:

40 weeks for the double blind phase, 64 weeks including the Open Label Extension

Estimated Enrollment:

80

Estimated Study Start Date:

09/02/2021

Estimated Study Completion Date:

07/30/2023

Posting Last Modified Date:

05/05/2022

Date Study Added to alsconsortium.org:

11/02/2021
  • More Information

    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

  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    18

    Maximum Age:

    N/A

    Min Vital Capacity (% predicted normal):

    50

    Time since Symptom Onset:

    <24 months

    Time since Diagnosis:

    Can participants use Riluzole?

    Yes


    Inclusion Criteria

    • Male and female participants. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
    • 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 patients, a confirmed pathogenic SOD1 mutation.
    • Onset of symptoms i.e., weakness within past 24 months prior to screening, at the time of obtaining informed consent.
    • Have SVC of ≥50% of predicted values. Participants with SVC of <50% of predicted values may be permitted to enter the OLE, 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 for at least 30 days prior to baseline (randomization) and remain on a stable dose throughout the study. Riluzole cannot be initiated during the double‑blind phase of the study. Riluzole can be initiated during the OLE after Week 3 if needed based on the opinion of the investigator and the dose may be adjusted as appropriate.
    • If on edaravone, must have completed 2 cycles at baseline (randomization) and are expected to remain on the same dose throughout the study. Edaravone cannot be initiated once the participant is randomized and for the duration of the double‑blind phase of the study. Edaravone can be initiated during the OLE after Week 3 if needed based on the opinion of the investigator and the dose may be adjusted as appropriate.
    • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
    • Have venous access sufficient to allow for blood sampling as per protocol.
    • Have clinical laboratory test results within 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.
    • Are able to visit the study site for outpatient treatment.
    • Are willing to make themselves available for the duration of the study and are willing to follow study specific procedures.

    Exclusion Criteria

    • Are investigator or site personnel affiliated with this study, or the immediate family of any of these. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
    • Are participating in or have participated in another clinical trial (or have taken an experimental therapy within the context of a clinical trial) within 5 half-lives 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 severe active psychiatric illness.
    • Have a diagnosis of another neurodegenerative disease (e.g., Parkinson’s disease, Alzheimer’s disease).
    • Have a significant pulmonary disorder not attributed to ALS or who require treatments that might complicate the evaluation of the effect of ALS on respiratory function.
    • Have cognitive impairment, severe disease in the renal, cardiovascular or hematological system.
    • Pregnant or nursing women.
    • Have been exposed to any antisense treatment targeting SOD1 within 6 months of the baseline visit or have known allergies or reactions to AP-101 or any of its excipients.
    • Have undergone stem cell therapy.
    • In the opinion of the investigator or sponsor, are unsuitable for inclusion in the study for any reason.

  • Site Contact Information

    UC San Diego
    Danielle Vaporean-Bussey / .(JavaScript must be enabled to view this email address) / La Jolla, California 92037
    United States

    Hospital for Special Surgery (HSS)
    Shara Holzberg / .(JavaScript must be enabled to view this email address) / New York, New York 10021
    United States

    University of Alberta
    Study Coordinator / 780-492-7690
    Edmonton, Alberta
    Canada

    Montreal Neurological Institute and Hospital
    Matthias Couillard / .(JavaScript must be enabled to view this email address) / Montréal, Quebec
    Canada

    Medizinische Hochschule Hannover
    Michaela Schwippert / .(JavaScript must be enabled to view this email address) / Hannover,
    Germany

    Universitätsklinikum Ulm
    Sabine Raubold / .(JavaScript must be enabled to view this email address) / Ulm,
    Germany

    Hanyang University Medical Center
    Bugyeong Son / .(JavaScript must be enabled to view this email address) / Seoul,
    South Korea

    Sabbatsberg sjukhus
    Charlotta Molin Edlund / .(JavaScript must be enabled to view this email address) / Stockholm,
    Sweden

    Norrlands universitetssjukhus
    Erica Almgren Stenberg / .(JavaScript must be enabled to view this email address) / Umeå,
    Sweden