The purpose of this study is to evaluate the safety, tolerability, and the immunological effects of adeno-associated virus-like particle human papillomavirus (AAVLP-HPV) vaccine in healthy adults.
2A Pharma's AAVLP-HPV vaccine candidate is based on AAVLPs with insertion of sequences of the L2 minor HPV capsid protein. The vaccine's intended clinical use is as a vaccine for prophylaxis against HPV infection in adolescents and adults. This is a 12 month single-center, randomized, placebo-controlled, double-blind, repeated dose, safety, tolerability, and immunological effect study. Twenty (20) healthy, adult male and female subjects will be enrolled with a minimum of 40% of each gender. Sixteen (16) subjects will be randomized to receive the active drug and 4 subjects to receive the placebo. At least 1 subject of each gender will be randomized to receive the placebo. Subjects will receive a total of 3 doses of AAVLP-HPV or placebo: a prime on Day 1, and two boosts, one on Day 57 (±2 days) and one on Day 180 (±1 week). The volunteers will be followed until day 365 (±1 week) when they return for the final safety and serum-based immunogenicity and neutralising antibodies assessment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
20
20μg/injection formulated in a ready to use solution containing 100mM sodium citrate, 2.5 mM MgCl2, 0.001% pluronic F-68, pH 6.0 for i.m. injection as 0.5 mL per injection.
0.5 mL 100 mM Sodium Citrate, 2.5 mM MgCl2, 0.001% Pluronic F-68, pH 6 for i.m. injection as 0.5 mL per injection.
Celerion Inc.
Belfast, Co.Antrim, United Kingdom
Percentage of Subjects Reporting Solicited Local Symptoms
Solicited local symptoms assessed including pain, tenderness, redness, swelling, and induration.
Time frame: Day 0 and 1 after each vaccination
Percentage of Subjects Reporting Solicited General Symptoms
Solicited general symptoms assessed including fever, headache, fatigue, nausea, diarrhea, vomiting, myalgia, allergic reaction.
Time frame: Through 365 days
Percentage of Subjects Reporting Unsolicited Adverse Events (AEs)
An unsolicited adverse event is defined as any adverse event (AE) reported in addition to those solicited during the clinical study.
Time frame: Through 365 days
Percentage of Subjects Reporting New Onset of Chronic Illness (NOCI)
A NOCI is defined as diagnosis post study drug administration of a new medical condition, which is chronic in nature, including those potentially controllable by medication (e.g., diabetes, asthma)
Time frame: Through 365 days
Percentage of Subjects Reporting Adverse Events of Special Interest (AESI)
An AESI should not necessarily be classified to be a serious adverse event, even though the event may be clinically significant. If an AESI is reported, the Sponsor should be promptly informed and information relevant to the event should be promptly collected using the same process as that used for reporting serious adverse events. For this protocol, AESI includes demyelinating syndromes or neurological conditions such as complex regional pain or postural orthostatic tachycardia syndromes.
Time frame: Through 365 days
Percentage of Subjects Reporting Serious Adverse Events (SAEs)
SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
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Time frame: Through 365 days
Vital Signs - Body Temperature
Single measurements of body temperature 35.6 ≤ Temperature ≤37.7 (C)
Time frame: Through 365 days
Vital Signs - Respiratory Rate
Measurements of respiratory rate 8≤ Respiration ≤24 (breaths/min)
Time frame: Through 365 days
Vital Signs - Blood Pressure
Measurements of blood pressure 90≤ Systolic ≤140 (mmHg) and 40≤ Diastolic ≤90 (mmHg
Time frame: Through 365 days
Vital Signs - Heart Rate
Measurements of 40≤ Pulse ≤99 (beats/min)
Time frame: Through 365 days
Vital Signs - Body Mass Index (BMI
Calculated as weight in kg / height in meters\^2
Time frame: Through 365 days
Electrocardiogram (ECG)
Single 12-lead ECGs will be performed. Measurement type must be one of the following: HR (50≤HR≤100 \[beats/min\]\], PR (110≤PR≤219 \[ms\]), QRS (QRS\<110 \[ms\]), QT, QTcF (QTcF for Male\<460 and for Female\<470 \[ms\]), or overall interpretation.
Time frame: Through 365 days
Physical examination
A full best practice physical examination will be performed by the PI
Time frame: Through 365 days
Clinical Laboratory Tests
Measurements of clinical laboratory abnormalities
Time frame: Through 365 days
Evaluation of immunogenicity using a humoral immune function ELISA assay from serum
Immunogenicity is measured as having generated anti-HPV type16 L2 and HPV type 31 L2 antibodies after vaccination. The antibody response is measured as a titer.
Time frame: Through 365 days
Evaluation of HPV-Neutralizing Antibodies using an in vitro Pseudovirion-Based HPV-Neutralization Assay (PBNA)
Neutralization is measured as having induced anti-HPV antibodies able to protect/neutralize HPV infection in vitro. The neutralization antibody titers are presented as the IC50 titer.
Time frame: Through 365 days