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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05344989
• Other study ID #: APNmAb005-101
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 6, 2022
• Est. completion date: July 2024

Study information

• Verified date: June 2023
• Source: APRINOIA Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: July 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Healthy Volunteers
• Tauopathies

Intervention

Drug:
• APNmAb005
Administered by IV infusion
• Placebo
Administered by IV infusion

Locations

Country	Name	City	State
United States	Collaborative Neuroscience Research, LLC., 2600 Redondo Ave.	Long Beach	California

Sponsors (1)

Lead Sponsor	Collaborator
APRINOIA Therapeutics, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Number of participants with Vital Sign Abnormalities	Measured by systolic and diastolic blood pressures, pulse rate, respiratory rate and body temperature.	Day 70
Primary	Number of participants with Electrocardiogram (ECG) Abnormalities	Measured by 12-lead ECG	Day 70
Primary	Number of participants with Clinical Laboratory Abnormalities	Measured by hematology, coagulation, serum chemistry and urinalysis.	Day 70
Secondary	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
Secondary	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
Secondary	Cmax of APNmAb005 in blood	Maximum observed plasma concentration of APNmAb005. Measured by blood sample analysis	Thru Day 70
Secondary	Cmax of APNmAb005 in CSF	Maximum observed plasma concentration of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis.	Thru Day 14
Secondary	Tmax of APNmAb005 in blood	Time to maximum observed plasma concentration following APNmAb005 administration. Measured by blood sample analysis	Thru Day 70
Secondary	Tmax of APNmAb005 in CSF	Time to maximum observed plasma concentration following APNmAb005 administration. Measured by cerebrospinal fluid (CSF) sample analysis.	Thru Day 14
Secondary	t1/2 of APNmAb005 in plasma	Terminal phase half-life of APNmAb005. Measured by blood sample analysis	Thru Day 70
Secondary	t1/2 of APNmAb005 in CSF	Terminal phase half-life of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis	Thru Day 14
Secondary	CL of APNmAb005 in blood.	Total body clearance of APNmAb005 from plasma. Measured by blood sample analysis	Thru Day 70
Secondary	CL of APNmAb005 in CSF	Total body clearance of APNmAb005 from plasma. Measured by cerebrospinal fluid (CSF) sample analysis	Thru Day 14
Secondary	Vd of APNmAb005 in plasma	Volume of distribution of APNmAb005. Measured by blood sample analysis	Thru Day 70
Secondary	Vd of APNmAb005 in CSF	Volume of distribution of APNmAb005. Measured by cerebrospinal fluid (CSF) sample analysis	Thru Day 14
Secondary	Number of participants with ADA formation against APNmAb005	Anti-drug antibody (ADA) presence measured by blood sample analysis	Thru Day 70
Secondary	Number of participants with no ADA formation against APNmAb005	Anti-drug antibody (ADA) presence measured by blood sample analysis	Thru Day 70
Secondary	Mean Total tau concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Thru Day 70
Secondary	Mean change in Total tau concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Baseline and Day 70
Secondary	Mean Total tau concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Thru Day 14
Secondary	Mean change in Total tau concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Baseline and Day 14
Secondary	Mean p-tau 181 concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Thru Day 70
Secondary	Mean change in p-tau 181 concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Baseline and Day 70
Secondary	Mean p-tau 181 concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Thru Day 14
Secondary	Mean change in p-tau 181 concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Baseline and Day 14
Secondary	Mean p-tau 217 concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Thru Day 70
Secondary	Mean change in p-tau 217 concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Baseline and Day 70
Secondary	Mean p-tau 217 concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Thru Day 14
Secondary	Mean change in p-tau 217 concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Baseline and Day 14
Secondary	Mean p-tau 231 concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Thru Day 70
Secondary	Mean change in p-tau 231 concentration in plasma	Pharmacodynamic biomarker concentration measured by blood sample analysis	Baseline and Day 70
Secondary	Mean p-tau 231 concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Thru Day 14
Secondary	Mean change in p-tau 231 concentration in CSF	Pharmacodynamic biomarker concentration measured by CSF analysis	Baseline and Day 14