A Study to Evaluate, Safety, Tolerability, and PK of AP-101 in Participants With ALS

NCT05039099 | Completed Phase 2 Results 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 (3)

• Participants With Treatment-Emergent Adverse Events (TEAE) and Treatment-Emergent Serious Adverse Events (TESAE) During the Double-Blind Period

  Treatment-emergent adverse events were adverse events that began or worsened after the first dose of randomized study treatment during the double-blind period. Treatment-emergent serious adverse events met the protocol-defined criteria for seriousness. Participants experiencing more than one event within a category were counted once in that category. Results are presented separately for the sporadic ALS and SOD1-associated ALS cohorts.

  From the first dose through the 21-day follow-up after Week 24, approximately 27 weeks

• Number of Participants With Abnormalities in Vital Signs, Clinical Laboratory Assessments, Physical and Neurological Examinations, and Electrocardiograms

  Number of participants with at least one abnormality in vital signs, clinical laboratory assessments, physical examinations, neurological examinations, or electrocardiograms during the double-blind period. Participants could be included in more than one category; therefore, categories were not mutually exclusive. Results are presented separately for the sporadic ALS and SOD1-associated ALS cohorts.

  From the first dose through the 21-day follow-up after Week 24, approximately 27 weeks

• Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) During the Double-Blind Period

  Serum samples were assessed for anti-drug antibodies to AP-101. Participants were evaluable for treatment-emergent anti-drug antibodies if they had at least one non-missing baseline result and at least one non-missing post-baseline result. One participant was anti-drug-antibody positive at baseline and subsequently tested negative; baseline positivity was not classified as treatment-emergent. Results are presented separately for the sporadic ALS and SOD1-associated ALS cohorts. ADA testing was not assessed in placebo participants.

  From baseline through the 21-day follow-up after Week 24, approximately 27 weeks

Secondary Outcomes (6)

• Model-Derived Elimination Half-Life of AP-101 in Serum

  From the first AP-101 dose through 16 weeks after the final AP-101 dose, up to approximately 64 weeks

• Model-Derived Area Under the Serum AP-101 Concentration-Time Curve

  AUC following the second active dose: Day 2 through Day 22; AUC at steady state: the 21-day dosing interval following the participant's final active AP-101 dose, which occurred up to approximately Week 48 of the study

• Model-Derived Maximum Serum AP-101 Concentration

  Cmax following the second active dose: Day 2 through Day 22; Cmax at steady state: during the 21-day dosing interval following the participant's final active AP-101 dose, which occurred up to approximately Week 48 of the study.

• AP-101 Concentration in Cerebrospinal Fluid During the Double-Blind Period

  Week 12 and Week 24 of the double-blind period

• Change From Baseline in Cerebrospinal Fluid Phosphorylated Neurofilament Heavy Chain (pNfH) During the Double-Blind Period

  Baseline to Week 24 of the double-blind period

Study Arms (2)

AP-101

EXPERIMENTAL

AP-101 is administered by intravenous infusion (IV).

Drug: AP-101

Placebo

PLACEBO COMPARATOR

Placebo is administered by intravenous infusion (IV).

Drug: Placebo

Interventions

AP-101 DRUG

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

AP-101

Placebo DRUG

Participants receive placebo by intravenous infusion (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 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 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

Charité

Berlin, 13353, Germany

Location

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

Bonn, 53127, Germany

Location

Hannover Medical School

Hanover, 30625, Germany

Location

Ulm University Hospital

Ulm, 89081, Germany

Location

Hanyang University Medical Center

Seoul, 04763, South Korea

Location

Studieenheten Akademiskt specialistcentrum, SLSO

Stockholm, 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

Limitations and Caveats

This Phase 2a study was designed primarily to evaluate safety and tolerability. Pharmacokinetics and the neurofilament biomarkers; phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain (NfL) were secondary endpoints. Clinical efficacy measures and other biomarkers were exploratory. Interpretation may be limited by small cohort sizes, no adjustment for multiplicity, and crossover and attrition in the optional open-label extension.

Results Point of Contact

• Title: Dr. Rakhee Ganti, Director of Medical Affairs
• Organization: AL-S Pharma

rakhee.ganti@al-spharma.com

16782962263

Study Officials

• Study Director

  AL-S Pharma AG

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: September 30, 2026
• Results First Posted: September 30, 2026

Record last verified: 2026-09

Locations

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