This is a Phase 1, first-in-human (FIH), double-blinded, placebo-controlled study where healthy subjects are randomly allocated to receive APNmAb005 or placebo. Approximately 5 dosing groups (cohorts) are planned with 8 subjects (randomized to 6 active: 2 placebo) per cohort. the starting dose of APNmAb005 is 5 mg/kg and the anticipated doses for subsequent cohorts are 10, 25, 50 and 70 mg/kg. A Safety Review Team (SRT) will review data on an ongoing basis throughout the study and before progression to the next dose level cohort. Subjects will receive a single dose of either APNmAb005 or placebo administered as a single IV infusion on Day 1 of the study and will remain in the study center until Day 3 (48 hours after dosing). They will return to the study center for 7 outpatient visits. The duration of the study, excluding screening, is approximately 71 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
40
Collaborative Neuroscience Research, LLC., 2600 Redondo Ave.
Long Beach, California, United States
Number of subjects with Adverse Events (AEs)
Defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Data collected by subject observations and data collected on AE page of electronic Case Report Form (eCRF), or other documents relevant to subject safety.
Time frame: Day 70
Number of subjects with Treatment-emergent AEs (TEAEs)
Defined as any event not present before exposure to study drug or any event already present that worsens in intensity or frequency after exposure. Data collected by subject observations and data collected on AE page of electronic Case Report Form (eCRF), or other documents relevant to subject safety.
Time frame: Day 70
Number of subjects with Serious Adverse Events (SAEs)
Defined as any AE for which there is a reasonable possibility that the study drug caused the AE. Data collected by subject observations and data collected on AE page of electronic Case Report Form (eCRF), or other documents relevant to subject safety.
Time frame: Day 70
Number of subjects with AEs resulting in Study Discontinuation
Data collected by subject observations and data collected on AE page of electronic Case Report Form (eCRF), or other documents relevant to subject safety.
Time frame: Day 70
Number of participants with Vital Sign Abnormalities
Measured by systolic and diastolic blood pressures, pulse rate, respiratory rate and body temperature.
Time frame: Day 70
Number of participants with Electrocardiogram (ECG) Abnormalities
Measured by 12-lead ECG
Time frame: Day 70
Number of participants with Clinical Laboratory Abnormalities
Measured by hematology, coagulation, serum chemistry and urinalysis.
Time frame: Day 70
AUC0-t of APNmAb005 in plasma
Area under the curve from time zero to last quantifiable concentration of APNmAb005. Measured by blood sample analysis.
Time frame: Thru Day 70
AUC0-t of APNmAb005 in CSF
Area under the curve from time zero to last quantifiable concentration of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis.
Time frame: Thru Day 14
Cmax of APNmAb005 in blood
Maximum observed plasma concentration of APNmAb005. Measured by blood sample analysis
Time frame: Thru Day 70
Cmax of APNmAb005 in CSF
Maximum observed plasma concentration of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis.
Time frame: Thru Day 14
Tmax of APNmAb005 in blood
Time to maximum observed plasma concentration following APNmAb005 administration. Measured by blood sample analysis
Time frame: Thru Day 70
Tmax of APNmAb005 in CSF
Time to maximum observed plasma concentration following APNmAb005 administration. Measured by cerebrospinal fluid (CSF) sample analysis.
Time frame: Thru Day 14
t1/2 of APNmAb005 in plasma
Terminal phase half-life of APNmAb005. Measured by blood sample analysis
Time frame: Thru Day 70
t1/2 of APNmAb005 in CSF
Terminal phase half-life of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis
Time frame: Thru Day 14
CL of APNmAb005 in blood.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Total body clearance of APNmAb005 from plasma. Measured by blood sample analysis
Time frame: Thru Day 70
CL of APNmAb005 in CSF
Total body clearance of APNmAb005 from plasma. Measured by cerebrospinal fluid (CSF) sample analysis
Time frame: Thru Day 14
Vd of APNmAb005 in plasma
Volume of distribution of APNmAb005. Measured by blood sample analysis
Time frame: Thru Day 70
Vd of APNmAb005 in CSF
Volume of distribution of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis
Time frame: Thru Day 14
Number of participants with ADA formation against APNmAb005
Anti-drug antibody (ADA) presence measured by blood sample analysis
Time frame: Thru Day 70
Number of participants with no ADA formation against APNmAb005
Anti-drug antibody (ADA) presence measured by blood sample analysis
Time frame: Thru Day 70
Mean Total tau concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time frame: Thru Day 70
Mean change in Total tau concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time frame: Baseline and Day 70
Mean Total tau concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Time frame: Thru Day 14
Mean change in Total tau concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Time frame: Baseline and Day 14
Mean p-tau 181 concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time frame: Thru Day 70
Mean change in p-tau 181 concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time frame: Baseline and Day 70
Mean p-tau 181 concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Time frame: Thru Day 14
Mean change in p-tau 181 concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Time frame: Baseline and Day 14
Mean p-tau 217 concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time frame: Thru Day 70
Mean change in p-tau 217 concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time frame: Baseline and Day 70
Mean p-tau 217 concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Time frame: Thru Day 14
Mean change in p-tau 217 concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Time frame: Baseline and Day 14
Mean p-tau 231 concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time frame: Thru Day 70
Mean change in p-tau 231 concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time frame: Baseline and Day 70
Mean p-tau 231 concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Time frame: Thru Day 14
Mean change in p-tau 231 concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Time frame: Baseline and Day 14