A First-in-Human Study to Assess Single Doses of APNmAb005 in Healthy Participants
Primary Purpose
Healthy Volunteers, Tauopathies, Alzheimer Disease
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
APNmAb005
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Healthy Volunteers focused on measuring Healthy Volunteers, Alzheimer's Disease, Alzheimer Disease, AD, Tauopathies, Tau
Eligibility Criteria
Inclusion Criteria:
- Body Mass Index (BMI) of 18.5 to 32 kg/m² inclusive, at screening.
- Female subjects of childbearing potential must use an acceptable method of birth control from screening until at least 90 days after study drug dosing; OR be surgically sterile; OR be postmenopausal. All female subjects must have a negative pregnancy test at screening and before the first dose of the study drug. Female subjects must also agree to refrain from egg donation during the study and for at least 90 days after study drug dosing.
- Male subjects must agree to use a condom when sexually active with a female partner of childbearing potential during the study and for at least 90 days after study drug dosing (or be surgically sterile); OR agree to practice abstinence during the study and for at least 90 days after study drug dosing. Male subjects must also agree to refrain from sperm donation during the study and for at least 90 days after study drug dosing.
- Agree to comply with all protocol requirements.
- Provide written informed consent.
Exclusion Criteria:
- Unable or unwilling to undergo venipuncture or tolerate venous access, or is unable or unwilling to undergo lumbar puncture.
- Has any significant acute or chronic medical illness that would impact the subject's ability to complete all study requirements or impact assessment of study data; or subject as had a clinically significant illness within 30 days prior to study drug dosing.
- Any medical condition or documented history that is a contraindication to lumbar puncture (e.g. bleeding disorder, spinal deformity).
- Positive COVID-19 molecular diagnostic test result at screening or prior to study drug dosing; or subject has known or suspected consequence from prior COVID-19 infection.
- History of cardiac, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal or oncogenic (with the exception of resected skin basal cell carcinoma) disease within 5 years prior to screening).
NOTE: Subjects with treated stable psychiatric conditions (e.g. anxiety, depression) are not allowed.
- Clinically significant neurological or psychiatric disorder.
- Major surgery, as determined by investigator, within 4 weeks prior to study drug dosing.
- Systolic blood pressure >140 mm Hg and/or diastolic blood pressure >90 mm Hg.
- Received any vaccine or used any prescription or over-the-counter medications (except paracetamol [up to 2 g per day]), including herbal or nutritional supplements, within 14 days prior to study drug dosing.
- Consumed caffeine- or xanthine-containing products within 48 hours prior to study drug dosing.
- Subject is a smoker or has regularly used nicotine or nicotine-containing products (e.g. snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) within 3 months prior to study drug dosing.
- Subject is involved in vigorous or strenuous physical activity or contact sports within 24 hours prior to study drug dosing.
- Subject has donated blood or blood products >450 mL within 3 months prior to study drug dosing.
- Significant
Other protocol-defined inclusion/exclusion criteria may apply.
Sites / Locations
- Collaborative Neuroscience Research, LLC., 2600 Redondo Ave.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
APNmAb005 (5mg/kg) vs Placebo
APNmAb005 (10 mg/kg) vs Placebo
APNmAb005 (25 mg/kg) vs Placebo
APNmAb005 (50 mg/kg) vs Placebo
APNmAb005 (70 mg/kg) vs Placebo
Arm Description
Single Ascending Dose (SAD)
Single Ascending Dose (SAD)
Single Ascending Dose (SAD)
Single Ascending Dose (SAD)
Single Ascending Dose (SAD)
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
Number of participants with Vital Sign Abnormalities
Measured by systolic and diastolic blood pressures, pulse rate, respiratory rate and body temperature.
Number of participants with Electrocardiogram (ECG) Abnormalities
Measured by 12-lead ECG
Number of participants with Clinical Laboratory Abnormalities
Measured by hematology, coagulation, serum chemistry and urinalysis.
Secondary Outcome Measures
AUC0-t of APNmAb005 in plasma
Area under the curve from time zero to last quantifiable concentration of APNmAb005. Measured by blood sample analysis.
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.
Cmax of APNmAb005 in blood
Maximum observed plasma concentration of APNmAb005. Measured by blood sample analysis
Cmax of APNmAb005 in CSF
Maximum observed plasma concentration of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis.
Tmax of APNmAb005 in blood
Time to maximum observed plasma concentration following APNmAb005 administration. Measured by blood sample analysis
Tmax of APNmAb005 in CSF
Time to maximum observed plasma concentration following APNmAb005 administration. Measured by cerebrospinal fluid (CSF) sample analysis.
t1/2 of APNmAb005 in plasma
Terminal phase half-life of APNmAb005. Measured by blood sample analysis
t1/2 of APNmAb005 in CSF
Terminal phase half-life of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis
CL of APNmAb005 in blood.
Total body clearance of APNmAb005 from plasma. Measured by blood sample analysis
CL of APNmAb005 in CSF
Total body clearance of APNmAb005 from plasma. Measured by cerebrospinal fluid (CSF) sample analysis
Vd of APNmAb005 in plasma
Volume of distribution of APNmAb005. Measured by blood sample analysis
Vd of APNmAb005 in CSF
Volume of distribution of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis
Number of participants with ADA formation against APNmAb005
Anti-drug antibody (ADA) presence measured by blood sample analysis
Number of participants with no ADA formation against APNmAb005
Anti-drug antibody (ADA) presence measured by blood sample analysis
Mean Total tau concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Mean change in Total tau concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Mean Total tau concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Mean change in Total tau concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Mean p-tau 181 concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Mean change in p-tau 181 concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Mean p-tau 181 concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Mean change in p-tau 181 concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Mean p-tau 217 concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Mean change in p-tau 217 concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Mean p-tau 217 concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Mean change in p-tau 217 concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Mean p-tau 231 concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Mean change in p-tau 231 concentration in plasma
Pharmacodynamic biomarker concentration measured by blood sample analysis
Mean p-tau 231 concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Mean change in p-tau 231 concentration in CSF
Pharmacodynamic biomarker concentration measured by CSF analysis
Full Information
NCT ID
NCT05344989
First Posted
April 19, 2022
Last Updated
June 13, 2023
Sponsor
APRINOIA Therapeutics, LLC
1. Study Identification
Unique Protocol Identification Number
NCT05344989
Brief Title
A First-in-Human Study to Assess Single Doses of APNmAb005 in Healthy Participants
Official Title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of APNmAb005 in Healthy Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 6, 2022 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
APRINOIA Therapeutics, LLC
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Volunteers, Tauopathies, Alzheimer Disease
Keywords
Healthy Volunteers, Alzheimer's Disease, Alzheimer Disease, AD, Tauopathies, Tau
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
APNmAb005 (5mg/kg) vs Placebo
Arm Type
Active Comparator
Arm Description
Single Ascending Dose (SAD)
Arm Title
APNmAb005 (10 mg/kg) vs Placebo
Arm Type
Active Comparator
Arm Description
Single Ascending Dose (SAD)
Arm Title
APNmAb005 (25 mg/kg) vs Placebo
Arm Type
Active Comparator
Arm Description
Single Ascending Dose (SAD)
Arm Title
APNmAb005 (50 mg/kg) vs Placebo
Arm Type
Active Comparator
Arm Description
Single Ascending Dose (SAD)
Arm Title
APNmAb005 (70 mg/kg) vs Placebo
Arm Type
Active Comparator
Arm Description
Single Ascending Dose (SAD)
Intervention Type
Drug
Intervention Name(s)
APNmAb005
Intervention Description
Administered by IV infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered by IV infusion
Primary Outcome Measure Information:
Title
Number of subjects with Adverse Events (AEs)
Description
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
Title
Number of subjects with Treatment-emergent AEs (TEAEs)
Description
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
Title
Number of subjects with Serious Adverse Events (SAEs)
Description
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
Title
Number of subjects with AEs resulting in Study Discontinuation
Description
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
Title
Number of participants with Vital Sign Abnormalities
Description
Measured by systolic and diastolic blood pressures, pulse rate, respiratory rate and body temperature.
Time Frame
Day 70
Title
Number of participants with Electrocardiogram (ECG) Abnormalities
Description
Measured by 12-lead ECG
Time Frame
Day 70
Title
Number of participants with Clinical Laboratory Abnormalities
Description
Measured by hematology, coagulation, serum chemistry and urinalysis.
Time Frame
Day 70
Secondary Outcome Measure Information:
Title
AUC0-t of APNmAb005 in plasma
Description
Area under the curve from time zero to last quantifiable concentration of APNmAb005. Measured by blood sample analysis.
Time Frame
Thru Day 70
Title
AUC0-t of APNmAb005 in CSF
Description
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
Title
Cmax of APNmAb005 in blood
Description
Maximum observed plasma concentration of APNmAb005. Measured by blood sample analysis
Time Frame
Thru Day 70
Title
Cmax of APNmAb005 in CSF
Description
Maximum observed plasma concentration of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis.
Time Frame
Thru Day 14
Title
Tmax of APNmAb005 in blood
Description
Time to maximum observed plasma concentration following APNmAb005 administration. Measured by blood sample analysis
Time Frame
Thru Day 70
Title
Tmax of APNmAb005 in CSF
Description
Time to maximum observed plasma concentration following APNmAb005 administration. Measured by cerebrospinal fluid (CSF) sample analysis.
Time Frame
Thru Day 14
Title
t1/2 of APNmAb005 in plasma
Description
Terminal phase half-life of APNmAb005. Measured by blood sample analysis
Time Frame
Thru Day 70
Title
t1/2 of APNmAb005 in CSF
Description
Terminal phase half-life of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis
Time Frame
Thru Day 14
Title
CL of APNmAb005 in blood.
Description
Total body clearance of APNmAb005 from plasma. Measured by blood sample analysis
Time Frame
Thru Day 70
Title
CL of APNmAb005 in CSF
Description
Total body clearance of APNmAb005 from plasma. Measured by cerebrospinal fluid (CSF) sample analysis
Time Frame
Thru Day 14
Title
Vd of APNmAb005 in plasma
Description
Volume of distribution of APNmAb005. Measured by blood sample analysis
Time Frame
Thru Day 70
Title
Vd of APNmAb005 in CSF
Description
Volume of distribution of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis
Time Frame
Thru Day 14
Title
Number of participants with ADA formation against APNmAb005
Description
Anti-drug antibody (ADA) presence measured by blood sample analysis
Time Frame
Thru Day 70
Title
Number of participants with no ADA formation against APNmAb005
Description
Anti-drug antibody (ADA) presence measured by blood sample analysis
Time Frame
Thru Day 70
Title
Mean Total tau concentration in plasma
Description
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time Frame
Thru Day 70
Title
Mean change in Total tau concentration in plasma
Description
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time Frame
Baseline and Day 70
Title
Mean Total tau concentration in CSF
Description
Pharmacodynamic biomarker concentration measured by CSF analysis
Time Frame
Thru Day 14
Title
Mean change in Total tau concentration in CSF
Description
Pharmacodynamic biomarker concentration measured by CSF analysis
Time Frame
Baseline and Day 14
Title
Mean p-tau 181 concentration in plasma
Description
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time Frame
Thru Day 70
Title
Mean change in p-tau 181 concentration in plasma
Description
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time Frame
Baseline and Day 70
Title
Mean p-tau 181 concentration in CSF
Description
Pharmacodynamic biomarker concentration measured by CSF analysis
Time Frame
Thru Day 14
Title
Mean change in p-tau 181 concentration in CSF
Description
Pharmacodynamic biomarker concentration measured by CSF analysis
Time Frame
Baseline and Day 14
Title
Mean p-tau 217 concentration in plasma
Description
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time Frame
Thru Day 70
Title
Mean change in p-tau 217 concentration in plasma
Description
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time Frame
Baseline and Day 70
Title
Mean p-tau 217 concentration in CSF
Description
Pharmacodynamic biomarker concentration measured by CSF analysis
Time Frame
Thru Day 14
Title
Mean change in p-tau 217 concentration in CSF
Description
Pharmacodynamic biomarker concentration measured by CSF analysis
Time Frame
Baseline and Day 14
Title
Mean p-tau 231 concentration in plasma
Description
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time Frame
Thru Day 70
Title
Mean change in p-tau 231 concentration in plasma
Description
Pharmacodynamic biomarker concentration measured by blood sample analysis
Time Frame
Baseline and Day 70
Title
Mean p-tau 231 concentration in CSF
Description
Pharmacodynamic biomarker concentration measured by CSF analysis
Time Frame
Thru Day 14
Title
Mean change in p-tau 231 concentration in CSF
Description
Pharmacodynamic biomarker concentration measured by CSF analysis
Time Frame
Baseline and Day 14
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Body Mass Index (BMI) of 18.5 to 32 kg/m² inclusive, at screening.
Female subjects of childbearing potential must use an acceptable method of birth control from screening until at least 90 days after study drug dosing; OR be surgically sterile; OR be postmenopausal. All female subjects must have a negative pregnancy test at screening and before the first dose of the study drug. Female subjects must also agree to refrain from egg donation during the study and for at least 90 days after study drug dosing.
Male subjects must agree to use a condom when sexually active with a female partner of childbearing potential during the study and for at least 90 days after study drug dosing (or be surgically sterile); OR agree to practice abstinence during the study and for at least 90 days after study drug dosing. Male subjects must also agree to refrain from sperm donation during the study and for at least 90 days after study drug dosing.
Agree to comply with all protocol requirements.
Provide written informed consent.
Exclusion Criteria:
Unable or unwilling to undergo venipuncture or tolerate venous access, or is unable or unwilling to undergo lumbar puncture.
Has any significant acute or chronic medical illness that would impact the subject's ability to complete all study requirements or impact assessment of study data; or subject as had a clinically significant illness within 30 days prior to study drug dosing.
Any medical condition or documented history that is a contraindication to lumbar puncture (e.g. bleeding disorder, spinal deformity).
Positive COVID-19 molecular diagnostic test result at screening or prior to study drug dosing; or subject has known or suspected consequence from prior COVID-19 infection.
History of cardiac, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal or oncogenic (with the exception of resected skin basal cell carcinoma) disease within 5 years prior to screening).
NOTE: Subjects with treated stable psychiatric conditions (e.g. anxiety, depression) are not allowed.
Clinically significant neurological or psychiatric disorder.
Major surgery, as determined by investigator, within 4 weeks prior to study drug dosing.
Systolic blood pressure >140 mm Hg and/or diastolic blood pressure >90 mm Hg.
Received any vaccine or used any prescription or over-the-counter medications (except paracetamol [up to 2 g per day]), including herbal or nutritional supplements, within 14 days prior to study drug dosing.
Consumed caffeine- or xanthine-containing products within 48 hours prior to study drug dosing.
Subject is a smoker or has regularly used nicotine or nicotine-containing products (e.g. snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) within 3 months prior to study drug dosing.
Subject is involved in vigorous or strenuous physical activity or contact sports within 24 hours prior to study drug dosing.
Subject has donated blood or blood products >450 mL within 3 months prior to study drug dosing.
Other protocol-defined inclusion/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Reynolds, DO
Organizational Affiliation
Collaborative Neuroscience Research, LLC.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Collaborative Neuroscience Research, LLC., 2600 Redondo Ave.
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A First-in-Human Study to Assess Single Doses of APNmAb005 in Healthy Participants
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