Clinical trial NCT04062669: A Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Experimental Rabies Vaccine in Healthy Adults
Official title: Safety and Immunogenicity of GSK's Rabies G SAM (CNE) Vaccine [GSK3903133A] in Healthy Adults.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Virus Diseases
Keywords: First Time in Human
Vaccine
Healthy subjects
Rabies
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2019-08-20
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: The purpose of this first time-in-human (FTiH) study is to evaluate the safety, reactogenicity and immunogenicity of different dose levels of an experimental rabies glycoprotein G (RG) vaccine (RG-SAM \[CNE\] vaccine), made using a new technology, when administered intramuscularly (IM) on a 0, 2, 6 \*-month schedule to healthy adults.

\* There will be no vaccinations with the third dose of any of the study treatments.


Eligibility criteria: Inclusion Criteria:

* Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. participation in genetics research, completion of the electronic diary cards, return for follow-up visits).
* Written informed consent obtained from the participant prior to performance of any study specific procedure.
* Healthy participants as established by medical history and clinical examination before entering into the study.
* A male or female participant between, and including, 18 and 40 years of age at the time of the first vaccination.
* Body Mass Index \>18 Kg/m\^2 and \<35 Kg/m\^2.
* Participants with following hematological/biochemical parameters:

  * White Blood Cells and differential, within the study designated laboratory normal range. Participants with FDA toxicity grade 1 differential cell counts and considered not clinically significant may be enrolled at the discretion of the investigator, and with the review and approval of the medical monitor.
  * Platelets = 125,000 - 500,000 cells/mm\^3
  * Hemoglobin within normal range of the study designated laboratory
  * Alanine aminotransferase within the study designated laboratory normal range
  * Aspartate aminotransferase within the study designated laboratory normal range
  * Total bilirubin within the study designated laboratory normal range
  * Alkaline phosphatase within the study designated laboratory normal range
  * Serum creatinine less than or equal to 1.1 times study designated laboratory's upper normal limit .
  * Seronegative for hepatitis B surface antigen, hepatitis C virus antibodies, or human immunodeficiency virus antibodies
* Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
* Female participants of childbearing potential may be enrolled in the study, if the participant

  * has practiced adequate contraception for 30 days prior to vaccination, and
  * has a negative pregnancy test on the day of vaccination, and
  * has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series

Exclusion Criteria:

* History of diagnosis with rabies exposure, infection or disease.
* Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
* Family history of congenital or hereditary immunodeficiency.
* History of or current autoimmune disease.
* History of any reaction or hypersensitivity likely to be exacerbated by any components of RabAvert including polygeline, bovine gelatin, neomycin, chlortetracycline and amphotericin B, chicken protein, egg products or any other vaccine component.
* Lymphoproliferative disorder or malignancy within previous 5 years (excluding effectively treated non-melanotic skin cancer).
* Hypersensitivity to latex.
* History of Type I hypersensitivity reactions to any beta-lactam antibiotics (penicillin, aminopenicillins, cephalosporins and carbapenems).
* Any acute or chronic, clinically significant disease, as determined by physical examination, laboratory screening tests, subject personal report and/or General Physician (GP) information.
* Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before the first dose of study vaccines, or planned use during the study period.
* Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the vaccination and ending 30 days after (Influenza vaccine excluded).
* Previous vaccination with any licensed or investigational rabies vaccine.
* Administration of immunoglobulins and/or any blood products within the 3 months preceding the dose of study vaccine or planned administration during the study period.
* Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period within 6 months prior to the vaccine dose.
* Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule.
* Concomitant or planned administration of antimalarial drugs, to include hydroxychloroquine within 30 days of vaccination.
* Current anti-tuberculosis prophylaxis or therapy.
* Concurrently participating in another clinical study, at any time during the study period, in which the participant has been/will be exposed to an investigational or a non-investigational vaccine/product.
* Pregnant or lactating female participant.
* Female participant planning to become pregnant or planning to discontinue contraceptive precautions.
* Participants at a higher risk than the average US resident with regard to exposure to rabies, per the RabAvert package insert and rabies vaccination recommendations from the Centers for Disease Control (CDC).
* Participants with extensive tattoos covering deltoid region on both the arms that would preclude the assessment of local reactogenicity.
* Planned move to a location that will prohibit participating in the trial until study end.
* Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation.

Primary outcomes:
measure: Number of participants reporting solicited local adverse events (AEs) during the 7-day follow-up period after the first dose received in the Primary vaccination phase
timeFrame: During the 7-day follow-up period after the first dose (administered at Day 1)
measure: Number of participants reporting solicited local adverse events (AEs) during the 7-day follow-up period after the second dose received in the Primary vaccination phase
timeFrame: During the 7-day follow-up period after the second dose (administered at Day 61)
measure: Number of participants reporting solicited general AEs during the 7-day follow-up period after the first dose received in the Primary vaccination phase
timeFrame: During the 7-day follow-up period after the first dose (administered at Day 1)
measure: Number of participants reporting solicited general AEs during the 7-day follow-up period after the second dose received in the Primary vaccination phase
timeFrame: During the 7-day follow-up period after the second dose (administered at Day 61)
measure: Number of participants reporting unsolicited AEs during a 30-day follow-up period follow-up after the first dose received in the Primary vaccination phase
timeFrame: During the 30-day follow-up period after the first dose (administered at Day 1).
measure: Number of participants reporting unsolicited AEs during a 30-day follow-up period follow-up after the second dose received in the Primary vaccination phase
timeFrame: During the 30-day follow-up period after the second dose (administered at Day 61).
measure: Number of participants with hematological and biochemical laboratory abnormalities at Day 1.
timeFrame: At Day 1
measure: Number of participants with hematological and biochemical laboratory abnormalities at Day 4.
timeFrame: At Day 4.
measure: Number of participants with hematological and biochemical laboratory abnormalities at Day 8.
timeFrame: At Day 8.
measure: Number of participants with hematological and biochemical laboratory abnormalities at Day 61.
timeFrame: At Day 61.
measure: Number of participants with hematological and biochemical laboratory abnormalities at Day 64.
timeFrame: At Day 64.
measure: Number of participants with hematological and biochemical laboratory abnormalities at Day 68.
timeFrame: At Day 68.
measure: Number of participants reporting medically attended AE (MAEs)
timeFrame: During 90 days (from Day 1 to Day 91)
measure: Number of participants reporting serious adverse events (SAEs)
timeFrame: During 90 days (from Day 1 to Day 91)
measure: Number of participants reporting potential immune-mediated diseases (pIMDs)
timeFrame: During 90 days (from Day 1 to Day 91)
Secondary outcomes:
measure: Number of participants reporting solicited local adverse events (AEs) during the 7-day follow-up period after each vaccination received from Day 1 up to study conclusion at Month 18
timeFrame: During the 7-day follow-up period after the third dose (administered at Day 181)
measure: Number of participants reporting solicited general AEs during the 7-day follow-up period after each vaccination received from Day 1 up to study conclusion at Month 18
timeFrame: During the 7-day follow-up period after the third dose (administered at Day 181)
measure: Number of participants reporting unsolicited AEs during a 30-day follow-up period after each vaccination from Day 1 up to study conclusion at Month 18
timeFrame: During the 30-day follow-up period after the third dose (administered at Day 181)
measure: Number of participants with hematological and biochemical laboratory abnormalities at Day 1, Day 4, Day 8, Day 61, Day 64, Day 68, Day 181, Day 184 and Day 188
timeFrame: At Day 1, Day 4, Day 8, Day 61, Day 64, Day 68, Day 181, Day 184 and Day 188
measure: Number of participants reporting MAEs from Day 1 up to study conclusion at Month 14
timeFrame: From Day 1 up to study conclusion at Month 14
measure: Number of participants reporting SAEs from Day 1 up to study conclusion at Month 14
timeFrame: From Day 1 to up to study end at Month 14
measure: Number of participants reporting pIMDs from Day 1 up to study conclusion at Month 14
timeFrame: From Day 1 up to study conclusion at Month 14
measure: Evaluation of immunogenicity in terms of Rabies Virus Neutralizing Antibody (RVNA) concentrations
timeFrame: At Day 1 and Day 91
measure: Evaluation of immunogenicity in terms of Anti-rabies G IgG antibody concentrations
timeFrame: At Day 1 and Day 91
measure: Evaluation of persistence of immunogenicity in terms of anti-rabies G IgG antibody concentrations at 5 months after last vaccination
timeFrame: At Month 7 (i.e. 5 months after the last vaccination)
measure: Evaluation of persistence of immunogenicity in terms of anti-rabies G IgG antibody concentrations at 10 months after last vaccination
timeFrame: At Month 12 (i.e. 10 months after the last vaccination)
Other outcomes:
Locations:
city: South Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Lenexa
country: United States
facility: GSK Investigational Site
state: Kansas
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
Study officials:
affiliation: GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: