Back to resultsA Study to Evaluate, Safety, Tolerability, Pharmacodynamic (PD) Markers and Pharmacokinetics (PK) of AP-101 in Participants With Amyotrophic Lateral Sclerosis (ALS)
Primary Purpose
Amyotrophic Lateral Sclerosis
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AP-101
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring Familial Amyotrophic Lateral Sclerosis, Sporadic Amyotrophic Lateral Sclerosis
Eligibility Criteria
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
Sites / Locations
- UC San Diego, ACTRIRecruiting
- Department of Neurology, University HospitalsRecruiting
- ALS clinic at the Kaye Edmonton Clinic, University of AlbertaRecruiting
- London Health Sciences Centre - Victoria HospitalRecruiting
- ALS Research Sunnybrook Health Sciences CentreRecruiting
- Montreal Neurological Institute and Hospital / Dr GengeRecruiting
- Charité
- Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)Recruiting
- Hannover Medical SchoolRecruiting
- Ulm University HospitalRecruiting
- Hanyang University Medical CenterRecruiting
- Studieenheten Akademiskt specialistcentrum, SLSORecruiting
- Norrlands universitetssjukhus/ University Hospital of Northern Sweden (NUS)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AP-101
Placebo
Arm Description
AP-101 is administered by IV.
Placebo is administered by IV.
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, other situations.
Number of Participants with Abnormalities in Vital Signs, Clinical Laboratory Assessments, Physical and Neurological Examinations, Electrocardiograms (ECGs)
Secondary Outcome Measures
Elimination half-life (t1/2) of AP-101 in Serum
Area Under the Drug Concentration-Time Curve (AUC)
Concentration at End of Infusion (Cat EOI)
Change From Baseline in AP-101 Levels in the Cerebrospinal Fluid (CSF) up to Week 24
Change From Baseline in Neurofilament Light Chain and Phospho-Neurofilament Heavy Chain Levels in the Cerebrospinal Fluid (CSF) up to Week 51
Change From Baseline in Neurofilament Light Chain and Phospho-Neurofilament Heavy Chain Levels in Plasma up to Week 51
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05039099
Brief Title
A Study to Evaluate, Safety, Tolerability, Pharmacodynamic (PD) Markers and Pharmacokinetics (PK) of AP-101 in Participants With Amyotrophic Lateral Sclerosis (ALS)
Official Title
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 Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 2, 2021 (Actual)
Primary Completion Date
June 28, 2024 (Anticipated)
Study Completion Date
January 18, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AL-S Pharma
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
Familial Amyotrophic Lateral Sclerosis, Sporadic Amyotrophic Lateral Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
63 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AP-101
Arm Type
Experimental
Arm Description
AP-101 is administered by IV.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo is administered by IV.
Intervention Type
Drug
Intervention Name(s)
AP-101
Intervention Description
Participants receive AP-101 by intravenous infusion (IV).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants receive placebo by IV.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Description
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, other situations.
Time Frame
From start of the study up to Week 51
Title
Number of Participants with Abnormalities in Vital Signs, Clinical Laboratory Assessments, Physical and Neurological Examinations, Electrocardiograms (ECGs)
Time Frame
From start of the study up to Week 51
Secondary Outcome Measure Information:
Title
Elimination half-life (t1/2) of AP-101 in Serum
Time Frame
Predose up to Week 51
Title
Area Under the Drug Concentration-Time Curve (AUC)
Time Frame
Predose up to Week 51
Title
Concentration at End of Infusion (Cat EOI)
Time Frame
Week 24
Title
Change From Baseline in AP-101 Levels in the Cerebrospinal Fluid (CSF) up to Week 24
Time Frame
Baseline, up to Week 24
Title
Change From Baseline in Neurofilament Light Chain and Phospho-Neurofilament Heavy Chain Levels in the Cerebrospinal Fluid (CSF) up to Week 51
Time Frame
Baseline, up to Week 51
Title
Change From Baseline in Neurofilament Light Chain and Phospho-Neurofilament Heavy Chain Levels in Plasma up to Week 51
Time Frame
Baseline, up to Week 51
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Director: AL-S Pharma SA
Phone
3176517036
Email
choruspharma@lists.lilly.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
AL-S Pharma SA
Official's Role
Study Director
Facility Information:
Facility Name
UC San Diego, ACTRI
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
858-243-1319
Email
jravits@ucsd.edu
First Name & Middle Initial & Last Name & Degree
John Ravits
Facility Name
Department of Neurology, University Hospitals
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philip Van Damme
Facility Name
ALS clinic at the Kaye Edmonton Clinic, University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
AB T6G 1Z1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
Phone
780-248-1089
Email
wendyj@ualberta.ca
First Name & Middle Initial & Last Name & Degree
Wendy Johnston
Facility Name
London Health Sciences Centre - Victoria Hospital
City
London
State/Province
Ontario
ZIP/Postal Code
ON N6A 5W9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
Phone
519-663-3597
Email
Christen.Shoesmith@lhsc.on.ca
First Name & Middle Initial & Last Name & Degree
Christen Shoesmith
Facility Name
ALS Research Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
Email
Lorne.Zinman@sunnybrook.ca
First Name & Middle Initial & Last Name & Degree
Lorne Zinman, Dr
Facility Name
Montreal Neurological Institute and Hospital / Dr Genge
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3A 2B4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
Phone
514-398-8551
Email
rami.massie@mcgill.ca
First Name & Middle Initial & Last Name & Degree
Rami Massie, Dr
Facility Name
Charité
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
Email
thomas.meyer@charite.de
First Name & Middle Initial & Last Name & Degree
Thomas Meyer
Facility Name
Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrick Weydt
Facility Name
Hannover Medical School
City
Hanover
ZIP/Postal Code
30625
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
Email
Petri.Susanne@mh-hannover.de
First Name & Middle Initial & Last Name & Degree
Susanne Petri
Facility Name
Ulm University Hospital
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
Email
albert.ludolph@rku.de
First Name & Middle Initial & Last Name & Degree
Albert Ludolph
Facility Name
Hanyang University Medical Center
City
Seoul
ZIP/Postal Code
04763
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
Phone
+82-2-2290-8371
Email
kimsh1@hanyang.ac.kr
First Name & Middle Initial & Last Name & Degree
SeungHyun Kim
Facility Name
Studieenheten Akademiskt specialistcentrum, SLSO
City
Stockholm
ZIP/Postal Code
113 61
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
Phone
+46851771231
First Name & Middle Initial & Last Name & Degree
Caroline Ingre
Facility Name
Norrlands universitetssjukhus/ University Hospital of Northern Sweden (NUS)
City
Umeå
ZIP/Postal Code
SE- 901 85
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
Phone
+46725487410
First Name & Middle Initial & Last Name & Degree
Peter Munch Andersen
12. IPD Sharing Statement
Learn more about this trial
A Study to Evaluate, Safety, Tolerability, Pharmacodynamic (PD) Markers and Pharmacokinetics (PK) of AP-101 in Participants With Amyotrophic Lateral Sclerosis (ALS)
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