A Phase I Study of PepGNP-ChikV in Healthy Volunteers

A Phase I, Dose-escalation, Randomized, Single-blind, Placebo-controlled Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of PepGNP-ChikV, a Synthetic Nanoparticle-based T Cell Next-generational Vaccine Against Chikungunya in Healthy Adults

This is a Phase I, randomized, single-blind, placebo-controlled, study of four separate dose cohorts, with a 42-day interval between each vaccine dose, of a novel Chikungunya Peptide Immunotherapy Vaccine in Healthy Adults (18-60 years of age).

All participants will undergo a screening visit scheduled for a maximum of 28 days before the enrolment in the clinical study and will provide a blood sample for clinical laboratory tests (complete blood count (CBC)*, platelet count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, serum creatinine and activated partial thromboplastin time (aPTT), human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV)), and a urine sample for tests for Urinary protein, Urinary blood, Urinary glucose and human chorionic gonadotropin β-subunit (βhCG) urine test (only the female participants)) in order to confirm their eligibility for participation in the study.

A total of 40 participants are planned to be enrolled. A randomization system will be used to assign treatment group and participant number at the clinical site.

Participants will receive 2 injections, 42 days apart. A final visit will take place at Day 407 (i.e. 365 days after last vaccination).

Participants will be kept under observation for a minimum of one hour after each vaccination to ensure their safety. Reactogenicity data will be collected in all participants after each vaccine injection: solicited injection site reactions will be collected for Days 0-10 and Days 42-52 and solicited systemic reactions will be collected for Days 0-21 and Days 42-63. Unsolicited events will be collected for Days 0-52. Serious adverse events (SAEs) will be reported throughout the study (from inclusion until 12 months after last vaccination). Serious and non-serious medically attended adverse events (MAAEs) and adverse events of special interest (AESIs) will be collected throughout the study (from inclusion until 12 months after last vaccination).

Inclusion Criteria:

1. Healthy individuals aged ≥18 years to ≤60 years of age, inclusive at time of consent, who are not receiving any excluded concomitant medications as detailed in protocol

2. Informed consent form signed.

3. Determined to be eligible by the Investigator based on medical history, physical examination, and screening laboratory testing.

4. Women of childbearing potential* are willing to use effective birth control method(s)** for a minimum of 14 days prior to dosing through 90 days after last study vaccination.

5. Male participants with a partner of childbearing potential must agree to use a highly effective method of contraception (e.g. sterilization or male condom) and refrain from sperm donation during the study and for at least 6 months after the last dose of study drug.

   • An individual who has experienced menarche and who is neither permanently surgically sterile (permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) nor post-menopausal. In line with the guidance provided by the Clinical Trial Facilitation Group (CTFG), a post-menopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

     • Females of childbearing potential and males must be willing to use a highly effective (acceptable effective contraceptive measures are only acceptable for IMPs with unlikely human teratogenicity / fetotoxicity in early pregnancy) method of contraception (hormonal or abstinence). Contraceptive methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include:

       • combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

       o oral

       o intravaginal

       o transdermal

       • progestogen-only hormonal contraception associated with inhibition of ovulation

       o oral

       o injectable

       o implantable

       • intrauterine device

       • intrauterine hormone-releasing system
       • bilateral tubal occlusion
       • vasectomised partner
       • sexual abstinence, (refraining from heterosexual intercourse during the entire period of risk associated with the study treatments (up to Day 407), if this is the preferred and usual lifestyle of the participant).

Exclusion Criteria:

1. Self-reported or documented history of laboratory-confirmed chikungunya or other mosquito-borne (arthropod) disease, such as Zika or dengue within 90 days prior to consent.
2. Travel in the previous 90 days to areas where exposure to flaviviruses such as Zika, dengue, West Nile Fever are common, as well as areas increasing in cases of chikungunya (refer to the following website: Chikungunya virus disease worldwide overview).
3. Self-reported or documented receipt of any chikungunya (alphavirus) or flavivirus vaccine (investigational or licensed) within 90 days prior to consent.
4. Receipt of any licensed vaccine, including COVID-19 vaccine, within the 28 days prior to consent or planned receipt within 90 days following last study vaccination (if unplanned circumstances subsequent to enrolment necessitate the receipt of a licensed vaccine e.g. tetanus and rabies, in unavoidable clinical settings, these should be documented in the source documents by the Investigator and not considered a protocol deviation. However, if the licensed vaccine is not urgently required, it should be delayed until at least 90 days following last study vaccination).
5. Known systemic hypersensitivity to any of the vaccine components (e.g. gold), or history of a life-threatening reaction to vaccines, or to a vaccine containing any of the same substances.
6. Acute illness according to Investigator judgment especially if febrile (≥38.0°C).
7. Screening laboratory testing, including vital signs, ECG, urinalysis and blood laboratory tests, must be within the normal reference ranges; if an isolated abnormality is reported, but is assessed by the Investigator as not clinically relevant the participant may be enrolled and the Investigator's judgement documented in the participant's source data. However, the following laboratory values must be within normal ranges: AST, ALT, bilirubin, all measures of renal function, neutrophil count and platelet count. If the Investigator suspects it to be an erroneous result, it can be repeated; the new result should be used for eligibility determination by the Investigator after documenting any clinical significance to any persistently abnormal result.
8. A positive SARS-CoV-2 polymerase chain reaction (PCR) or a positive rapid SARS-CoV-2 antigen test at Screening.
9. Women who are pregnant, or lactating,
10. Calculated body mass index (BMI) > 32.0 kg/m2.
11. Participation in another clinical study investigating a vaccine, drug, medical device, or medical procedure within 90 days or five half-lives, whichever is longer, prior to consent or planned participation in such a study during the period of this clinical study.
12. Receipt of immunoglobulins, blood or blood-derived products within 90 days prior to consent or planned receipt during the period of this chikungunya vaccine study.
13. Known or suspected congenital or acquired immunodeficiency or autoimmune disease; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy, within 90 days prior to consent; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within 90 days prior to consent).
14. Self-reported or documented Hepatitis surface antigen (HBsAg) positivity or antibody against human immunodeficiency virus (HIV), Hepatitis B core, or Hepatitis C. If the viral screening sample at the screening visit provides a positive result, the participant will be excluded.
15. Thrombocytopenia (platelet count <150,000/mL) or any coagulation disorder considered clinically significant by the Investigator.
16. Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or study completion.
17. Current alcohol abuse or drug addiction (reported or suspected).
18. Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study or identified as an immediate family member (i.e. parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study. (i.e. in the employment of the clinical study site).