Clinical trial NCT03981536: A Study to Evaluate AP-101 in Familial and Sporadic Amyotrophic Lateral Sclerosis (ALS)
Official title: A Multicenter, Open Label, Single-Ascending Dose Study to Evaluate Safety, Tolerability, and Pharmacokinetics of AP-101 in Familial and Sporadic Amyotrophic Lateral Sclerosis (ALS)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Familial Amyotrophic Lateral Sclerosis
Sporadic Amyotrophic Lateral Sclerosis
Lead sponsor: AL-S Pharma
Sponsor class: INDUSTRY
First posted: 2019-06-11
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Single ascending doses of AP-101 will be administered by intravenous (IV) infusion


Eligibility criteria: Inclusion Criteria:

* All participants must adhere to contraception restrictions
* Female patients of non-childbearing potential due to:

  1. Menopause: spontaneous amenorrhea for at least 12 months not induced by a medical conditions such as anorexia nervosa and not taking medications that induced the amenorrhea (e.g., oral contraceptives, hormones, gonadotropin releasing hormones, anti-estrogens, selective estrogen receptor modulators, or chemotherapy)
  2. Surgical sterilization
* Have possible, probable, probable laboratory supported or definite and definite familial laboratory-supported ALS in accordance with the El-Escorial criteria
* Have familial or sporadic ALS.
* With onset of ALS symptoms, specifically onset of muscle weakness within past 48 months
* Have slow vital capacity (SVC) of (greater than or equal to) ≥60%
* 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. If the patient is not able to provide written consent due to aggravation of disease condition, written informed consent may be provided by a legally authorized representative
* Have venous access sufficient to allow for blood sampling
* 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

Exclusion Criteria:

* Are currently enrolled in, or discontinued from, within the last 30 days, a clinical trial involving an investigational drug or device or off-label use of a drug or device, or any other type of medical research judged not to be scientifically or medically compatible with this study
* Have previously completed or withdrawn from this study
* Have a history or presence of medical illness including, but not limited to, any cognitive, cardiovascular, hepatic, hematological, renal, endocrine, or psychiatric, or any clinically significant laboratory abnormality that indicates a medical problem that would preclude study participation
* Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies
* Show evidence of hepatitis C and/or positive hepatitis C antibody
* Show evidence of hepatitis B and/or positive hepatitis B surface antigen
* Are women who are lactating.
* Have undergone a tracheostomy unless it was removed at least 6 months prior
* Are on feeding tube, unless the insertion of a feeding tube is considered prophylactic
* Are on nasal intermittent positive pressure ventilation (NIPPV) \>4 hours per day or at the discretion of the medical monitor
* Have undergone stem cell therapy

Primary outcomes:
measure: Number of Participants With One or More Non-Serious Adverse Events (AEs) or Any Serious AEs (SAEs)
timeFrame: Baseline up to day 84
measure: Number of participants with abnormalities in vital signs, clinical laboratory assessments, physical or neurological examinations, or electrocardiograms (ECGs)
timeFrame: Baseline up to day 84
Secondary outcomes:
measure: Maximum Observed Drug Concentration (Cmax)
timeFrame: Baseline up to day 84
measure: Time of Maximum Drug Concentration (Tmax)
timeFrame: Baseline up to day 84
measure: Area Under the Concentration Time Curve (AUC)
timeFrame: Baseline up to day 84
measure: Pharmacokinetic Concentrations in Cerebrospinal Fluid (CSF)
timeFrame: Screening, and at either 1 hour, 4 hours, 24 hours, 48 hours, 72 hours, or 168 hours
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Centre, University Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre, Toronto
state: Ontario
city: Montréal
country: Canada
facility: Montreal Neurological Institute & Hospital
state: Quebec
Study officials:
affiliation: AL-S Pharma SA
name: Study Director
role: STUDY_DIRECTOR
References: