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A Study of Safety, Tolerability and Immunogenicity of HPV-L2 Vaccine in Healthy Adult Male and Female Subjects

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ClinicalTrials.gov Identifier: NCT03929172
Recruitment Status : Recruiting
First Posted : April 26, 2019
Last Update Posted : April 26, 2019
Sponsor:
Collaborator:
Celerion
Information provided by (Responsible Party):
2A Pharma AB

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.

Condition or disease Intervention/treatment Phase
Papillomavirus Infections Biological: AAVLP-HPV Drug: Placebo Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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
Actual Study Start Date : February 28, 2019
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020

Arm Intervention/treatment
Experimental: 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).
Biological: AAVLP-HPV
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.
Other Name: 2AP01

Placebo Comparator: 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).
Drug: Placebo
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.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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)

  5. 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.

  6. 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.

  7. Vital Signs - Body Temperature [ Time Frame: Through 365 days ]
    Single measurements of body temperature 35.6 ≤ Temperature ≤37.7 (C)

  8. Vital Signs - Respiratory Rate [ Time Frame: Through 365 days ]
    Measurements of respiratory rate 8≤ Respiration ≤24 (breaths/min)

  9. Vital Signs - Blood Pressure [ Time Frame: Through 365 days ]
    Measurements of blood pressure 90≤ Systolic ≤140 (mmHg) and 40≤ Diastolic ≤90 (mmHg

  10. Vital Signs - Heart Rate [ Time Frame: Through 365 days ]
    Measurements of 40≤ Pulse ≤99 (beats/min)

  11. Vital Signs - Body Mass Index (BMI [ Time Frame: Through 365 days ]
    Calculated as weight in kg / height in meters^2

  12. 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.

  13. Physical examination [ Time Frame: Through 365 days ]
    A full best practice physical examination will be performed by the PI

  14. Clinical Laboratory Tests [ Time Frame: Through 365 days ]
    Measurements of clinical laboratory abnormalities


Secondary Outcome Measures :
  1. Evaluation of immunogenicity using a humoral immune function ELISA assay from serum [ Time Frame: Through 365 days ]
    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.

  2. Evaluation of HPV-Neutralizing Antibodies using an in vitro Pseudovirion-Based HPV-Neutralization Assay (PBNA) [ Time Frame: Through 365 days ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Subjects must fulfill all of the following inclusion criteria to be eligible for participation in the study:

  1. Healthy, adult, male or female aged between 18 and 45 years, inclusive, at screening.
  2. Body Mass Index (BMI) ≥ 18 and ≤ 32.0 kg/m2 at screening.
  3. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.
  4. 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.

  5. 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:

    • hysteroscopic sterilization;
    • bilateral tubal ligation or bilateral salpingectomy;
    • hysterectomy;
    • bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to the first dosing and follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status.
  6. Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.

Exclusion Criteria:

Subjects must not be enrolled in the study if they meet any of the following criteria:

  1. 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.
  2. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
  3. 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.
  4. History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.
  5. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds.
  6. Prior vaccination against HPV.
  7. Positive for HPV antibodies against HPV types 6, 11, 16, and 18.
  8. Have received an investigational vaccination within 90 days before screening.
  9. Have received any licensed vaccination within 30 days before screening.
  10. Any condition that may interfere with the intended administration of the study drug.
  11. Suffered from febrile or infectious illness within 7 days prior to Day 1.
  12. Subjects who plan to become pregnant/start a family during the study.
  13. Female subjects with a positive pregnancy test or who are lactating.
  14. Drink alcohol in excess of 21 glasses/units (425 g) per week for males or 14 glasses/units (284 g) per week for females, with one unit = 150 mL of wine or 360 mL of beer or 45 mL of 45% alcohol.
  15. Positive urine drug or alcohol results at screening or Day -1.
  16. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
  17. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.
  18. Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.
  19. QTcF interval is >460 msec (males) or >470 msec (females) or has ECG findings deemed abnormal with clinical significance by the PI or designee at screening.
  20. Unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements that could adversely affect the immune system during 3 months prior to vaccination and throughout the study. Inhaled and topical corticosteroids will be allowed. Medication listed as part of acceptable birth control methods and hormone replacement therapy will be allowed. After randomization, acetaminophen (up to 2 g per 24 hours) may be administered at the discretion of the PI or designee. Appropriate sources will be consulted by the PI or designee to confirm interaction with study drugs. Subjects may not initiate new prescription medication within 1 month prior to screening, with exceptions, or must be on a stable dose for at least 90 days prior to vaccination as approved in advance by the PI or designee.
  21. Donation of blood or plasma within 90 days prior to the first dosing.
  22. Donation of bone marrow within the last 6 months prior to the first dosing.
  23. Participation in another clinical study with an investigational agent within the 90 days prior to first dosing. The 90-day window will be derived from the date of the last dosing, whichever is later, in the previous study to Day 1 of the current study.
  24. Has tattoo(s) or scarring at or near the site of vaccine administration or any other condition which may interfere with injection site examination, in the opinion of the PI.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03929172


Contacts
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Contact: Fiona McNeilly +44 28 9055 4000 fiona.mcneilly@celerion.com

Locations
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United Kingdom
Celerion Inc. Recruiting
Belfast, Co.Antrim, United Kingdom, BT9 6AD
Contact: Fiona McNeilly         
Sponsors and Collaborators
2A Pharma AB
Celerion
Investigators
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Study Chair: John Nieland 2A Pharma AB
Principal Investigator: David Bell Celerion, CRO

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Responsible Party: 2A Pharma AB
ClinicalTrials.gov Identifier: NCT03929172     History of Changes
Other Study ID Numbers: 2AP01-01
2018-003045-42 ( EudraCT Number )
First Posted: April 26, 2019    Key Record Dates
Last Update Posted: April 26, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by 2A Pharma AB:
HPV-L2

Additional relevant MeSH terms:
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Papillomavirus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs