Clinical trial NCT05344989: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Healthy Volunteers
Tauopathies
Alzheimer Disease
Keywords: Healthy Volunteers
Alzheimer's Disease
Alzheimer Disease
AD
Tauopathies
Tau
Lead sponsor: APRINOIA Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-04-25
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of subjects with Adverse Events (AEs)
timeFrame: Day 70
measure: Number of subjects with Treatment-emergent AEs (TEAEs)
timeFrame: Day 70
measure: Number of subjects with Serious Adverse Events (SAEs)
timeFrame: Day 70
measure: Number of subjects with AEs resulting in Study Discontinuation
timeFrame: Day 70
measure: Number of participants with Vital Sign Abnormalities
timeFrame: Day 70
measure: Number of participants with Electrocardiogram (ECG) Abnormalities
timeFrame: Day 70
measure: Number of participants with Clinical Laboratory Abnormalities
timeFrame: Day 70
Secondary outcomes:
measure: AUC0-t of APNmAb005 in plasma
timeFrame: Thru Day 70
measure: AUC0-t of APNmAb005 in CSF
timeFrame: Thru Day 14
measure: Cmax of APNmAb005 in blood
timeFrame: Thru Day 70
measure: Cmax of APNmAb005 in CSF
timeFrame: Thru Day 14
measure: Tmax of APNmAb005 in blood
timeFrame: Thru Day 70
measure: Tmax of APNmAb005 in CSF
timeFrame: Thru Day 14
measure: t1/2 of APNmAb005 in plasma
timeFrame: Thru Day 70
measure: t1/2 of APNmAb005 in CSF
timeFrame: Thru Day 14
measure: CL of APNmAb005 in blood.
timeFrame: Thru Day 70
measure: CL of APNmAb005 in CSF
timeFrame: Thru Day 14
measure: Vd of APNmAb005 in plasma
timeFrame: Thru Day 70
measure: Vd of APNmAb005 in CSF
timeFrame: Thru Day 14
measure: Number of participants with ADA formation against APNmAb005
timeFrame: Thru Day 70
measure: Number of participants with no ADA formation against APNmAb005
timeFrame: Thru Day 70
measure: Mean Total tau concentration in plasma
timeFrame: Thru Day 70
measure: Mean change in Total tau concentration in plasma
timeFrame: Baseline and Day 70
measure: Mean Total tau concentration in CSF
timeFrame: Thru Day 14
measure: Mean change in Total tau concentration in CSF
timeFrame: Baseline and Day 14
measure: Mean p-tau 181 concentration in plasma
timeFrame: Thru Day 70
measure: Mean change in p-tau 181 concentration in plasma
timeFrame: Baseline and Day 70
measure: Mean p-tau 181 concentration in CSF
timeFrame: Thru Day 14
measure: Mean change in p-tau 181 concentration in CSF
timeFrame: Baseline and Day 14
measure: Mean p-tau 217 concentration in plasma
timeFrame: Thru Day 70
measure: Mean change in p-tau 217 concentration in plasma
timeFrame: Baseline and Day 70
measure: Mean p-tau 217 concentration in CSF
timeFrame: Thru Day 14
measure: Mean change in p-tau 217 concentration in CSF
timeFrame: Baseline and Day 14
measure: Mean p-tau 231 concentration in plasma
timeFrame: Thru Day 70
measure: Mean change in p-tau 231 concentration in plasma
timeFrame: Baseline and Day 70
measure: Mean p-tau 231 concentration in CSF
timeFrame: Thru Day 14
measure: Mean change in p-tau 231 concentration in CSF
timeFrame: Baseline and Day 14
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Collaborative Neuroscience Research, LLC., 2600 Redondo Ave.
state: California
Study officials:
affiliation: Collaborative Neuroscience Research, LLC
name: Steven Reynolds, DO
role: PRINCIPAL_INVESTIGATOR
References: