A Study to Assess the Safety, Reactogenicity and Immune Response of GlaxoSmithKline (GSK) Biologicals' Investigational Respiratory Syncytial Virus (RSV) Vaccine (GSK3844766A) in Older Adults

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Respiratory Syncytial Virus Infections

Treatments: Biological: RSV Vaccine (GSK3844766A) unadjuvanted low dose; Biological: RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E; Biological: RSV Vaccine (GSK3844766A) unadjuvanted high dose; Biological: RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01B; Biological: RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01B; Drug: Placebo (Saline solution); Biological: RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01B; Biological: RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01E; Biological: RSV Vaccine (GSK3844766A) unadjuvanted medium dose; Biological: RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01E

Study type: Interventional

Funder types: Industry

Identifiers

NCT03814590

2018-000849-38 (EudraCT Number)

208851

Details and patient eligibility

About

The purpose of this study is to assess the safety, reactogenicity and immune responses of two doses of the investigational RSV vaccines (with different formulations), when administered intramuscularly (IM) according to a 0, 2 month schedule, in older adults aged 60 to 80 years.

As the investigational vaccines have not yet been tested in humans before, the study will first assess the safety, reactogenicity and immune responses in young adults aged 18 to 40 years. The study will thus be conducted in 2 parts (Part A and Part B).

Enrollment: 1,053 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

For all subjects:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written informed consent obtained from the subject prior to performing any study specific procedure.

For Part A:

• A male or female between, and including, 18 and 40 years of age at the time of the first vaccination.

For Part B:

• A male or female between, and including, 60 and 80 years of age at the time of the first vaccination.
• Subjects with residence status allowing free mixing with general community or in an assisted-living facility that provides minimal assistance, such that the subject is primarily responsible for self-care and activities of daily living.

Exclusion criteria

For all subjects:

• Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the first dose of study vaccine, or planned use during the study period.
• Any medical condition that in the judgment of the investigator would make IM injection unsafe.
• Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting 6 months prior to the first vaccine dose. For corticosteroids, this will mean prednisone (≥ 20 mg/day, or equivalent). Inhaled and topical steroids are allowed.
• Administration of long-acting immune-modifying drugs or planned administration at any time during the study period.
• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of study vaccine administration, with the exception of inactivated and subunit influenza vaccines which can be administered up to 14 days before or from 30 days after each study vaccination.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• Hypersensitivity to latex.
• Serious or unstable chronic illness. Patients with chronic stable conditions with or without specific treatment, such as diabetes, hypertension or cardiac disease, are allowed to participate in this study.
• Any other condition (e.g. chronic obstructive pulmonary disease or severe respiratory condition) that, in the opinion of the investigator, might interfere with the evaluations required by the study.
• History of any neurological disorders or seizures.
• Acute disease and/or fever at the time of enrolment.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by the investigator based on medical history, physical examination or laboratory screening tests.
• Hepatomegaly, right upper quadrant abdominal pain or tenderness.
• Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccine or planned administration during the study period.
• History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.
• Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study.
• Previous vaccination with an RSV vaccine.
• Lymphoproliferative disorder and malignancy within 5 years.
• Body mass index > 40 kg/m².
• Planned move to a location that will prohibit participating in the trial until study end.
• At screening: Hematology parameters (complete blood cell count [red blood cells, white blood cells], white blood cells differential count [lymphocytes, neutrophils and eosinophils], platelets count or hemoglobin level) and/or biochemistry parameters (creatinine, blood urea nitrogen or liver enzymes [alanine aminotransferase or aspartate aminotransferase]) outside the normal laboratory ranges, unless the laboratory abnormalities are considered not clinically significant by the investigator.

For Part A:

• Pregnant or lactating female.

• Female subjects of childbearing potential, except if the subject:

  • 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.

For Part B:

• Known previous administration of a vaccine containing MPL, QS-21 and/or MF59 (e.g. GSK Biologicals' vaccine against human papillomavirus infection marketed as Cervarix, GSK Biologicals' Herpes Zoster vaccine marketed as Shingrix, an adjuvanted recombinant varicella zoster virus envelope gE subunit vaccine [HZ/su], or MF59 adjuvanted influenza vaccines [e.g. Fluad]).
• Planned administration of GSK Biologicals' Herpes Zoster vaccine marketed as Shingrix or an adjuvanted recombinant varicella zoster virus envelope gE subunit vaccine [HZ/su] within 180 days after the second dose of the study vaccine.
• Bedridden subjects.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,053 participants in 14 patient groups, including a placebo group

Group Low Dose_PLAIN_A

Experimental group

Description:

Subjects in Part A, aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted low dose on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Treatment:

Biological: RSV Vaccine (GSK3844766A) unadjuvanted low dose

Group Medium Dose_PLAIN_A

Experimental group

Description:

Subjects in Part A aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted medium dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Treatment:

Biological: RSV Vaccine (GSK3844766A) unadjuvanted medium dose

Group High Dose_PLAIN_A

Experimental group

Description:

Subjects in Part A aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted high dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Treatment:

Biological: RSV Vaccine (GSK3844766A) unadjuvanted high dose

Group Placebo_A

Placebo Comparator group

Description:

Subjects in Part A aged 18-40 years, receiving 2 doses of placebo (saline solution) control, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Treatment:

Drug: Placebo (Saline solution)

Group Low Dose_PLAIN_B

Experimental group

Description:

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted low dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Treatment:

Biological: RSV Vaccine (GSK3844766A) unadjuvanted low dose

Group Low Dose_AS01E_B

Experimental group

Description:

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Treatment:

Biological: RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01E

Group Low Dose_AS01B_B

Experimental group

Description:

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Treatment:

Biological: RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01B

Group Medium Dose_PLAIN_B

Experimental group

Description:

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted medium dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Treatment:

Biological: RSV Vaccine (GSK3844766A) unadjuvanted medium dose

Group Medium Dose_AS01E_B

Experimental group

Description:

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Treatment:

Biological: RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01E

Group Medium Dose_AS01B_B

Experimental group

Description:

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Treatment:

Biological: RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01B

Group High Dose_PLAIN_B

Experimental group

Description:

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted high dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Treatment:

Biological: RSV Vaccine (GSK3844766A) unadjuvanted high dose

Group High Dose_AS01E_B

Experimental group

Description:

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Treatment:

Biological: RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E

Group High Dose_AS01B_B

Experimental group

Description:

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Treatment:

Biological: RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01B

Group Placebo_B

Placebo Comparator group

Description:

Subjects in Part B aged 60-80 years, receiving 2 doses of placebo (saline solution) control, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Treatment:

Drug: Placebo (Saline solution)