A First-in-Human, Phase 1, Randomized, Placebo-Controlled, Double-Blind Study to Assess the Safety and Tolerability, and to Explore Immunological Effects of I.M. Administered AAVLP-HPV Vaccine in Healthy Adult Male and Female Subjects
Overview
- Phase
- Phase 1
- Intervention
- AAVLP-HPV
- Conditions
- Papillomavirus Infections
- Sponsor
- 2A Pharma AB
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Vital Signs - Blood Pressure
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must fulfill all of the following inclusion criteria to be eligible for participation in the study:
- •Healthy, adult, male or female aged between 18 and 45 years, inclusive, at screening.
- •Body Mass Index (BMI) ≥ 18 and ≤ 32.0 kg/m2 at screening.
- •Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.
- •For a female of childbearing potential: either be sexually inactive (abstinent as a lifestyle\*) for 28 days prior to the first dosing and throughout the study or be using one of the following acceptable birth control methods:
- •hormonal oral contraceptives, vaginal ring, transdermal patch, or hormone releasing intrauterine device for at least 3 months prior to the first dosing with either a physical (e.g., condom, diaphragm, or other) or a chemical (e.g., spermicide) barrier method from the time of screening and throughout the study.
- •depot/implantable hormone (e.g., Depo-provera®, Implanon) for at least 3 months prior to the first dosing and throughout the study.
- •In addition, female subjects of childbearing potential will be advised to remain sexually inactive or to keep the same birth control method for at least 28 days following the last dose.
- •\* True abstinence is defined as refraining from heterosexual intercourse in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to study drug, and withdrawal are not acceptable methods of contraception.
- •For a female of non-childbearing potential: must have undergone one of the following sterilization procedures at least 6 months prior to the first dosing:
Exclusion Criteria
- •Subjects must not be enrolled in the study if they meet any of the following criteria:
- •Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
- •History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
- •History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
- •History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.
- •History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds.
- •Prior vaccination against HPV.
- •Positive for HPV antibodies against HPV types 6, 11, 16, and
- •Have received an investigational vaccination within 90 days before screening.
- •Have received any licensed vaccination within 30 days before screening.
Arms & Interventions
AAVLP-HPV Vaccine Arm
Subjects will receive a total of 3 vaccinations: a prime on Day 1, and boosts on Day 57 (± 2 days) and Day 180 (± 1 week).
Intervention: AAVLP-HPV
Placebo Arm
Subjects will receive a total of 3 vaccinations: a prime on Day 1, and boosts on Day 57 (± 2 days) and Day 180 (± 1 week).
Intervention: Placebo
Outcomes
Primary Outcomes
Vital Signs - Blood Pressure
Time Frame: Through 365 days
Measurements of blood pressure 90≤ Systolic ≤140 (mmHg) and 40≤ Diastolic ≤90 (mmHg
Vital Signs - Heart Rate
Time Frame: Through 365 days
Measurements of 40≤ Pulse ≤99 (beats/min)
Percentage of Subjects Reporting Unsolicited Adverse Events (AEs)
Time Frame: Through 365 days
An unsolicited adverse event is defined as any adverse event (AE) reported in addition to those solicited during the clinical study.
Percentage of Subjects Reporting New Onset of Chronic Illness (NOCI)
Time Frame: Through 365 days
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)
Percentage of Subjects Reporting Serious Adverse Events (SAEs)
Time Frame: Through 365 days
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.
Percentage of Subjects Reporting Solicited General Symptoms
Time Frame: Through 365 days
Solicited general symptoms assessed including fever, headache, fatigue, nausea, diarrhea, vomiting, myalgia, allergic reaction.
Percentage of Subjects Reporting Solicited Local Symptoms
Time Frame: Day 0 and 1 after each vaccination
Solicited local symptoms assessed including pain, tenderness, redness, swelling, and induration.
Percentage of Subjects Reporting Adverse Events of Special Interest (AESI)
Time Frame: Through 365 days
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.
Vital Signs - Body Temperature
Time Frame: Through 365 days
Single measurements of body temperature 35.6 ≤ Temperature ≤37.7 (C)
Vital Signs - Respiratory Rate
Time Frame: Through 365 days
Measurements of respiratory rate 8≤ Respiration ≤24 (breaths/min)
Physical examination
Time Frame: Through 365 days
A full best practice physical examination will be performed by the PI
Vital Signs - Body Mass Index (BMI
Time Frame: Through 365 days
Calculated as weight in kg / height in meters\^2
Clinical Laboratory Tests
Time Frame: Through 365 days
Measurements of clinical laboratory abnormalities
Electrocardiogram (ECG)
Time Frame: Through 365 days
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.
Secondary Outcomes
- Evaluation of immunogenicity using a humoral immune function ELISA assay from serum(Through 365 days)
- Evaluation of HPV-Neutralizing Antibodies using an in vitro Pseudovirion-Based HPV-Neutralization Assay (PBNA)(Through 365 days)