A First-in-Human Study to Assess Single Doses of APNmAb005 in Healthy Participants

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

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 Overview

• Status: Active, not recruiting
• Conditions: Alzheimer Disease; Tauopathies; Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: APNmAb005

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Research, LLC., 2600 Redondo Ave.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: APNmAb005 (5mg/kg) vs Placebo; Single Ascending Dose (SAD)	Drug: Placebo; Administered by IV infusion; Drug: APNmAb005; Administered by IV infusion
Active Comparator: APNmAb005 (10 mg/kg) vs Placebo; Single Ascending Dose (SAD)	Drug: Placebo; Administered by IV infusion; Drug: APNmAb005; Administered by IV infusion
Active Comparator: APNmAb005 (25 mg/kg) vs Placebo; Single Ascending Dose (SAD)	Drug: Placebo; Administered by IV infusion; Drug: APNmAb005; Administered by IV infusion
Active Comparator: APNmAb005 (50 mg/kg) vs Placebo; Single Ascending Dose (SAD)	Drug: Placebo; Administered by IV infusion; Drug: APNmAb005; Administered by IV infusion
Active Comparator: APNmAb005 (70 mg/kg) vs Placebo; Single Ascending Dose (SAD)	Drug: Placebo; Administered by IV infusion; Drug: APNmAb005; Administered by IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Day 70
Number of participants with Vital Sign Abnormalities	Measured by systolic and diastolic blood pressures, pulse rate, respiratory rate and body temperature.	Day 70
Number of participants with Electrocardiogram (ECG) Abnormalities	Measured by 12-lead ECG	Day 70
Number of participants with Clinical Laboratory Abnormalities	Measured by hematology, coagulation, serum chemistry and urinalysis.	Day 70

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-t of APNmAb005 in plasma	Area under the curve from time zero to last quantifiable concentration of APNmAb005. Measured by blood sample analysis.	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.	Thru Day 14
Cmax of APNmAb005 in blood	Maximum observed plasma concentration of APNmAb005. Measured by blood sample analysis	Thru Day 70
Cmax of APNmAb005 in CSF	Maximum observed plasma concentration of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis.	Thru Day 14
Tmax of APNmAb005 in blood	Time to maximum observed plasma concentration following APNmAb005 administration. Measured by blood sample analysis	Thru Day 70
Tmax of APNmAb005 in CSF	Time to maximum observed plasma concentration following APNmAb005 administration. Measured by cerebrospinal fluid (CSF) sample analysis.	Thru Day 14
t1/2 of APNmAb005 in plasma	Terminal phase half-life of APNmAb005. Measured by blood sample analysis	Thru Day 70
t1/2 of APNmAb005 in CSF	Terminal phase half-life of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis	Thru Day 14
CL of APNmAb005 in blood.	Total body clearance of APNmAb005 from plasma. Measured by blood sample analysis	Thru Day 70
CL of APNmAb005 in CSF	Total body clearance of APNmAb005 from plasma. Measured by cerebrospinal fluid (CSF) sample analysis	Thru Day 14
Vd of APNmAb005 in plasma	Volume of distribution of APNmAb005. Measured by blood sample analysis	Thru Day 70
Vd of APNmAb005 in CSF	Volume of distribution of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis	Thru Day 14
Number of participants with ADA formation against APNmAb005	Anti-drug antibody (ADA) presence measured by blood sample analysis	Thru Day 70
Number of participants with no ADA formation against APNmAb005	Anti-drug antibody (ADA) presence measured by blood sample analysis	Thru Day 70
Mean Total tau concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Thru Day 70
Mean change in Total tau concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Baseline and Day 70
Mean Total tau concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Thru Day 14
Mean change in Total tau concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Baseline and Day 14
Mean p-tau 181 concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Thru Day 70
Mean change in p-tau 181 concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Baseline and Day 70
Mean p-tau 181 concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Thru Day 14
Mean change in p-tau 181 concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Baseline and Day 14
Mean p-tau 217 concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Thru Day 70
Mean change in p-tau 217 concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Baseline and Day 70
Mean p-tau 217 concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Thru Day 14
Mean change in p-tau 217 concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Baseline and Day 14
Mean p-tau 231 concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Thru Day 70
Mean change in p-tau 231 concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Baseline and Day 70
Mean p-tau 231 concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Thru Day 14
Mean change in p-tau 231 concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Baseline and Day 14

Collaborators and Investigators

• Sponsor: APRINOIA Therapeutics, LLC
• Investigators: Principal Investigator: Steven Reynolds, DO, Collaborative Neuroscience Research, LLC.

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2022
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: April 19, 2022
• First Submitted That Met QC Criteria: April 19, 2022
• First Posted (Actual): April 25, 2022

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Healthy Volunteers; Alzheimer Disease; AD; Tau; Tauopathies
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Alzheimer Disease; Tauopathies
• Other Study ID Numbers: APNmAb005-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No