A Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Experimental Rabies Vaccine in Healthy Adults

NCT04062669 | Completed Phase 1 FDA Drug

• 1 other identifier: 208608
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 4

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.

Conditions

Virus Diseases

Keywords

First Time in Human; Vaccine; Healthy subjects; Rabies

Outcome Measures

Primary Outcomes (15)

• 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

  The following local AEs are solicited: pain, redness and swelling at injection site.

  During the 7-day follow-up period after the first dose (administered at Day 1)

• 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

  The following local AEs are solicited: pain, redness and swelling at injection site.

  During the 7-day follow-up period after the second dose (administered at Day 61)

• Number of participants reporting solicited general AEs during the 7-day follow-up period after the first dose received in the Primary vaccination phase

  The following general AEs are solicited: fatigue, fever, nausea, vomiting, diarrhea, abdominal pain and headache. Fever is defined as temperature ≥ 38.0°C / 100.4°F. The preferred location for measuring temperature in this study is the oral cavity.

  During the 7-day follow-up period after the first dose (administered at Day 1)

• Number of participants reporting solicited general AEs during the 7-day follow-up period after the second dose received in the Primary vaccination phase

  The following general AEs are solicited: fatigue, fever, nausea, vomiting, diarrhea, abdominal pain and headache. Fever is defined as temperature ≥ 38.0°C / 100.4°F. The preferred location for measuring temperature in this study is the oral cavity.

  During the 7-day follow-up period after the second dose (administered at Day 61)

• 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

  Unsolicited AE is defined as an AE reported in addition to those solicited during the clinical study and as any solicited AE with onset outside the specified period of follow-up for solicited symptoms.

  During the 30-day follow-up period after the first dose (administered at Day 1).

• 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

  Unsolicited AE is defined as an AE reported in addition to those solicited during the clinical study and as any solicited AE with onset outside the specified period of follow-up for solicited symptoms.

  During the 30-day follow-up period after the second dose (administered at Day 61).

• Number of participants with hematological and biochemical laboratory abnormalities at Day 1.

  Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.

  At Day 1

• Number of participants with hematological and biochemical laboratory abnormalities at Day 4.

  Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.

  At Day 4.

• Number of participants with hematological and biochemical laboratory abnormalities at Day 8.

  Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.

  At Day 8.

• Number of participants with hematological and biochemical laboratory abnormalities at Day 61.

  Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.

  At Day 61.

• Number of participants with hematological and biochemical laboratory abnormalities at Day 64.

  Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.

  At Day 64.

• Number of participants with hematological and biochemical laboratory abnormalities at Day 68.

  Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.

  At Day 68.

• Number of participants reporting medically attended AE (MAEs)

  A medically attended adverse event is an AE for which the participants received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (i.e., nurse practitioner or physician assistant or medical doctor) for any reason.

  During 90 days (from Day 1 to Day 91)

• Number of participants reporting serious adverse events (SAEs)

  SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study patient.

  During 90 days (from Day 1 to Day 91)

• Number of participants reporting potential immune-mediated diseases (pIMDs)

  pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.

  During 90 days (from Day 1 to Day 91)

Secondary Outcomes (11)

• 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

  During the 7-day follow-up period after the third dose (administered at Day 181)

• 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

  During the 7-day follow-up period after the third dose (administered at Day 181)

• 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

  During the 30-day follow-up period after the third dose (administered at Day 181)

• 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

  At Day 1, Day 4, Day 8, Day 61, Day 64, Day 68, Day 181, Day 184 and Day 188

• Number of participants reporting MAEs from Day 1 up to study conclusion at Month 14

  From Day 1 up to study conclusion at Month 14

Study Arms (6)

Low dose (Ld-) RG SAM (CNE) group

EXPERIMENTAL

In Part 1 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) low dose formulation vaccine in one arm and one intramuscular injection of saline solution in the opposite arm at Days 1 and 61). In Part 2 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) low dose formulation vaccine in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61)

Biological: Low dose formulation of RG SAM (CNE) vaccine (GSK3903133A)

Medium dose (Md-) RG SAM (CNE) group

EXPERIMENTAL

Healthy adults,18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) medium dose formulation vaccine in one arm and one intramuscular injection of saline solution in the opposite arm at Day 1.

Biological: Medium dose formulation of RG SAM (CNE) vaccine (GSK3903133A)

Lower dose (Lrd-) RG SAM (CNE) group

EXPERIMENTAL

Healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) lower dose formulation vaccine in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61)

Biological: Lower dose formulation of RG SAM (CNE) vaccine (GSK3903133A)

Lowest dose (Ltd-) RG SAM (CNE) group

EXPERIMENTAL

Healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) lowest dose formulation vaccine in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61)

Biological: Lowest dose formulation of RG SAM (CNE) vaccine (GSK3903133A)

Saline Placebo group

PLACEBO COMPARATOR

In Part 1 of the study, healthy adults, 18 to 40 years of age, will receive two intramuscular injections of saline placebo, one in each arm, according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61). In Part 2 of the study, healthy adults, 18 to 40 years of age will receive one intramuscular injections of saline placebo in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61).

Drug: Saline Placebo

RabAvert group

ACTIVE COMPARATOR

In Part 1 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RabAvert in one arm and one intramuscular injection of saline solution in the other arm, according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61). In Part 2 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RabAvert in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61).

Biological: RabAvert

Interventions

Low dose formulation of RG SAM (CNE) vaccine (GSK3903133A) BIOLOGICAL

Subjects in the low dose (Ld-) RG SAM (CNE) group will receive 2 doses of RG SAM (CNE) low dose formulation, administered intramuscularlyat Days 1 and 61.

Low dose (Ld-) RG SAM (CNE) group

Medium dose formulation of RG SAM (CNE) vaccine (GSK3903133A) BIOLOGICAL

Subjects in the medium dose (Md-) RG SAM (CNE) group will receive 1 doses of RG SAM (CNE) medium dose formulation, administered intramuscularly at Day 1.

Medium dose (Md-) RG SAM (CNE) group

Lower dose formulation of RG SAM (CNE) vaccine (GSK3903133A) BIOLOGICAL

Subjects in the Lower dose (Lrd-) RG SAM (CNE) group will receive 2 doses of RG SAM (CNE) lower dose formulation, administered intramuscularly, according to a 0, 2-month schedule (i.e. at Days 1 and 61)

Lower dose (Lrd-) RG SAM (CNE) group

Lowest dose formulation of RG SAM (CNE) vaccine (GSK3903133A) BIOLOGICAL

Subjects in the Lowest dose (Ltd-) RG SAM (CNE) group will receive 2 doses of RG SAM (CNE) lowest dose formulation, administered intramuscularly, according to a 0, 2-month schedule (i.e. at Days 1 and 61)

Lowest dose (Ltd-) RG SAM (CNE) group

Saline Placebo DRUG

Subjects in the Saline Placebo group will receive 2 doses of saline Placebo, administered intramuscularly Day 1 and 61.

Saline Placebo group

RabAvert BIOLOGICAL

Subjects in the RabAvert Group will receive 2 doses of RabAvert vaccine, administered intramuscularly, at Days 1 and 61.

RabAvert group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

South Miami, Florida, 33143, United States

Location

GSK Investigational Site

Lenexa, Kansas, 66219, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21201, United States

Location

GSK Investigational Site

Rochester, New York, 14609, United States

Location

MeSH Terms

Conditions

Virus Diseases; Rabies

Interventions

Vaccines

Condition Hierarchy (Ancestors)

Infections; Rhabdoviridae Infections; Mononegavirales Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: In Part 1 of the study, only data during the primary vaccination phase (from study start to Day 91) will be collected in an observer-blind manner. By observer-blind, it is meant that the vaccines recipient and those responsible for the evaluation of any study endpoint will all be unaware of which vaccine was administered. For Part 1, the study will be observer-blind until Day 91. When the Day 91 analysis will result in unblinding of all the subjects to the sponsor. Therefore, the study cannot be considered observer-blind beyond Day 91 and will be conducted in a single-blind\* manner thereafter; with all subjects remaining blinded up to study conclusion (Month 14). For Part 2, the study will be conducted in open-label manner from study start to study conclusion. \*Due to the recent COVID-19 pandemic, the study will be fully unblinded from study start to study conclusion to allow all subject treatments to be known to the team and investigators, thereby facilitating rapid safety assessment.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2019
• First Posted: August 20, 2019
• Study Start: August 13, 2019
• Primary Completion: July 28, 2021
• Study Completion: July 1, 2022
• Last Updated: March 1, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an exemption can be granted, when justified, for up to another 12 months.

Locations

US (4)