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)

Study Purpose:

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

Study Status:

Recruiting

Disease:

Amyotrophic Lateral Sclerosis

Study Type:

Interventional

Type of Intervention:

Drug

Intervention Name:

AP-101, Placebo

Placebo:

Yes

Phase:

Phase 2

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

Study Director, AL-S Pharma SA

Clinicaltrials.gov ID:

NCT05039099

Neals Affiliated?

No

Coordinating Center Contact Information

Montreal Neurological Institute and Hospital

Study Director: AL-S Pharma SA / email hidden; JavaScript is required / 3176517036

Canada

Study Sponsor:

AL-S Pharma

Participant Duration:

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

Estimated Enrollment:

63

Estimated Study Start Date:

09 / 02 / 2021

Estimated Study Completion Date:

07 / 30 / 2023

Posting Last Modified Date:

08 / 15 / 2022

Date Study Added to neals.org:

09 / 09 / 2021

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) 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

UC San Diego, ACTRI | Recruiting

/ 858-243-1319 / email hidden; JavaScript is required

Principal Investigator : John Ravits

La Jolla, California 92037
United States

ALS clinic at the Kaye Edmonton Clinic, University of Alberta | Recruiting

/ 780-248-1089 / email hidden; JavaScript is required

Principal Investigator : Wendy Johnston

Edmonton, Alberta AB T6G 1Z1
Canada

London Health Sciences Centre - Victoria Hospital | Recruiting

/ 519-663-3597 / email hidden; JavaScript is required

Principal Investigator : Christen Shoesmith

London, Ontario ON N6A 5W9
Canada

ALS Research Sunnybrook Health Sciences Centre | Recruiting

/ email hidden; JavaScript is required

Principal Investigator : Lorne Zinman, Dr

Toronto, Ontario M4N 3M5
Canada

Montreal Neurological Institute and Hospital / Dr Genge | Recruiting

/ 514-398-8551 / email hidden; JavaScript is required

Principal Investigator : Rami Massie, Dr

Montréal, Quebec H3A 2B4
Canada

Charité | Not yet recruiting

/ email hidden; JavaScript is required

Principal Investigator : Thomas Meyer

Berlin 13353
Germany

Hannover Medical School | Recruiting

/ email hidden; JavaScript is required

Principal Investigator : Susanne Petri

Hanover 30625
Germany

Ulm University Hospital | Recruiting

/ email hidden; JavaScript is required

Principal Investigator : Albert Ludolph

Ulm 89081
Germany

Hanyang University Medical Center | Recruiting

/ +82-2-2290-8371 / email hidden; JavaScript is required

Principal Investigator : SeungHyun Kim

Seoul 04763
Korea, Republic of

Studieenheten Akademiskt specialistcentrum, SLSO | Recruiting

/ +46851771231

Principal Investigator : Caroline Ingre

Stockholm 113 61
Sweden

Norrlands universitetssjukhus/ University Hospital of Northern Sweden (NUS) | Recruiting

/ +46725487410

Principal Investigator : Peter Munch Andersen

Umeå SE- 901 85
Sweden