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

Sponsor

APRINOIA Therapeutics, LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05344989

Collaborator

(none)

Enrollment

Location

Arms

7.9

Anticipated Duration (Months)

5.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers Tauopathies Alzheimer Disease	Drug: APNmAb005 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 6, 2022

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Number of subjects with Adverse Events (AEs) [Day 70]
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) [Day 70]
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) [Day 70]
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 [Day 70]
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 [Day 70]
Measured by systolic and diastolic blood pressures, pulse rate, respiratory rate and body temperature.
Number of participants with Electrocardiogram (ECG) Abnormalities [Day 70]
Measured by 12-lead ECG
Number of participants with Clinical Laboratory Abnormalities [Day 70]
Measured by hematology, coagulation, serum chemistry and urinalysis.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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