A Study of RSV-HMPV Bivalent Vaccine VXB-241 in Older Adults

Vicebio Australia Proprietary Limited

Status and phase: Active, not recruiting; Phase 1

Conditions: Healthy Volunteers

Treatments: Biological: VXB-241 240 mcg (Medium-high Dose); Biological: VXB-241 60 mcg (Low Dose); Other: Placebo; Biological: VXB-241 120 mcg (Medium Dose); Biological: VXB-241; Biological: Arexvy 120 mcg; Biological: VXB-241 480 mcg (High Dose)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06556147

VXB241-001

Details and patient eligibility

About

The main purposes of this study are to assess the safety, reactogenicity and immunogenicity of 4 dose levels of the bivalent combination Respiratory Syncytial Virus (RSV) / human Metapneumovirus (hMPV) vaccine candidate VXB-241 when administered as a single-dose regimen to healthy adults 60 to 83 years of age, and to assess the impact of revaccination approximately 1 year later.

Full description

This is a multi-center study in older adults with run-in in young adults to evaluate the safety, reactogenicity, and immunogenicity of 4 dose levels of VXB-241. The total planned sample size is 136 randomized participants, composed of 16 young adults 18 to 40 years of age and 120 older adults 60 to 83 years of age who are in good health, which allows for many chronic conditions, if well controlled and compatible with self-sufficiency in self-care and daily living activities.

Recruitment will be in 2 stages:

• Stage 1 (Sequential Cohort Stage, N=32). Four cohorts (Cohorts 1 to 4), each of 8 participants, will be enrolled sequentially. In each cohort, 4 young adults will be enrolled first, followed by 4 older adults. Young and older adult participants will be randomized with 3:1 ratio to VXB-241 at increasing dose (60 microgram (mcg), 120 mcg, 240 mcg, 480 mcg in Cohorts 1 to 4, respectively) or Placebo. A Safety Monitoring Committee will make recommendations on escalation from one cohort to the next and from Stage 1 to Stage 2 based on safety and reactogenicity data collected over 1 week after investigational medicinal product (IMP) dosing.
• Stage 2 (Concurrent Group Stage, N=104). Older adult participants will be randomized concurrently with unequal randomization to 1 of 6 treatment groups: VXB-241 60 mcg (Group 1a), VXB-241 120 mcg (1b), VXB-241 240 mcg (1c), VXB-241 480 mcg (1d), commercial RSV vaccine Arexvy (2a), Placebo (3a). The planned total sample size of each treatment group, combining Stage 1 and Stage 2, is N=20.

The overall planned duration of the study is approximately 6 months for young adult participants and approximately 2 years for older adult participants.

At the end of the 1st year, older adult participants will receive a second IMP vaccination (revaccination): participants who received VXB-241 (at any dose) will be assigned 1:1 to revaccination with VXB-241 (Group 1e) or Placebo (1f); participants who received Arexvy will be revaccinated with Arexvy (2b); participants who received Placebo will be revaccinated with VXB-241 (3b). The dose of VXB-241 for revaccination will be decided based on Year-1 results.

Enrollment: 144 patients

Sex: All

Ages: 18 to 83 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Male or female, 18 to 40 years of age (yoa) (young adult) or 60 to 83 yoa (older adult).
2. Evidence of signed and dated participant informed consent form (PICF) prior to any study procedure, indicating that the participant has been informed of all pertinent aspects of the study.
3. Willingness and ability to comply with the planned study visits and calls, procedures, and restrictions for the duration of the study.
4. Good health, which allows for pre-existing well-controlled and low impact chronic diseases, except for the diseases listed in the exclusion criteria. A disease is defined as well-controlled and low impact if it did not require meaningful change in therapy or unplanned medical visits in the previous 3 months and allows participant's primary responsibility for self-care and daily living activities.
5. Non-smoker or occasional smoker, defined as smoking less than 10 nicotine-containing cigarettes/ vapes/cigars/pipe fills per week.
6. Contraception: heterosexually active participants of childbearing potential able and willing to use a double contraceptive method for at least 4 weeks before and 12 weeks after the first IMP injection at Visit 2 (all participants of childbearing potential) and second IMP injection at Visit 6 (male older adults of childbearing potential).
7. Body Mass Index (BMI) >=17.0 kilogram per square meter (kg/m^2) and less than or equal to (<=) 35.0 kg/m^2.

Exclusion criteria

1. History of RSV and/or hMPV infection affecting the participant and/or the participant's household in the previous 12 months.

2. History of autoimmune disease (AID) or potentially autoimmune disease (pAID) requiring therapeutic intervention, even if stable and well controlled, including but not limited to systemic lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain-Barré syndrome, multiple sclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, temporal arteritis, psoriasis, insulin-dependent diabetes mellitus, celiac disease.

3. Confirmed or suspected immunodeficiency, even if stable and well controlled.

4. Ongoing severe asthma. Other allergic diseases (example, allergic rhinitis, atopic dermatitis / eczema, mild to moderate asthma, food allergies, are allowed at the investigator's or delegate's discretion).

5. History of severe allergic reaction (example, anaphylaxis) to any substance, including vaccine components and latex.

6. History of severe adverse event (AEs) associated with vaccine administration.

7. Ongoing disorders of coagulation, which contraindicate IM injections.

8. Donation or loss of >=500 milliliter (mL) whole blood on the previous 2 months and/or donation of plasma in the previous 1 week, and/or intention to donate blood or plasma during the study.

9. Positive serum test results for serum human immunodeficiency virus (HIV), hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection and/or documented HIV, HVB or HVC infection.

10. Other poorly controlled and/or impactful chronic disease. A disease is defined as poorly controlled if it required meaningful change in therapy and/or unplanned medical visits in the previous 3 months. A disease is defined as impactful if it has a meaningful impact on participant's self-care and/or activities of daily living.

11. Disease expected to prevent completion of the study (that is to rapidly deteriorate within the timeframe of the study).

12. Prior treatments.

    1. Licensed RSV vaccine or investigational RSV and/or hMPV vaccine received at any time.
    2. Investigational drug or vaccine received in the previous 6 months.
    3. Chemotherapy, radiotherapy, and/or other immunosuppressive medication including biologics received in the previous 6 months.
    4. Immunoglobulins G (IgGs) or any blood product received in the previous 3 months.
    5. Systemic corticosteroids (oral/intravenous/intramuscular) at doses equivalent to >=20 mg prednisone received for >=14 days, even if not consecutive, during the previous 3 months. Inhaled/nebulized, intra-articular, intra-bursal, skin and eye topical corticosteroids are permitted.

13. Clinically meaningful abnormal finding from physical examination, vital sign assessment, electrocardiogram (ECG), safety laboratory test results. If deemed appropriate, the investigator or delegate may repeat these assessments.

14. History of alcohol abuse in the previous year and/or positive alcohol breath test.

15. History of recreational drug abuse in the previous year and/or positive test for drugs of abuse, unless there is an explanation acceptable to the investigator (example, the participant has informed in advance that he/she consumed a prescription or over-the-counter product that contained the detected drug).

16. Intention to participate in any investigational drug/vaccine clinical trial at any time throughout the planned duration of this study.

17. Presence of tattoo, scarring, skin discoloration, or any other skin disturbances at the injection site which may interfere with effective assessment of the injection site.

18. Intention to move to a location that would prevent participating in the study until study end.

19. Limited to premenopausal female participants: breastfeeding, positive pregnancy test or intention to become pregnant during the first 3 months of the study.

20. Any other reason which would prevent the participant from participating in the study or interfere with the participant's compliance with study procedures.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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144 participants in 14 patient groups, including a placebo group

Stage 1, Day 1, Sequential Cohort 1

Experimental group

Description:

Young and older adult participants will receive VXB-241 60 mcg (low dose) or Placebo, intramuscularly (IM), once on Day 1.

Treatment:

Other: Placebo

Biological: VXB-241 60 mcg (Low Dose)

Stage 1, Day 1, Sequential Cohort 2

Experimental group

Description:

Young and older adult participants will receive VXB-241 120 mcg (medium dose) or Placebo, IM, once on Day 1.

Treatment:

Biological: VXB-241 120 mcg (Medium Dose)

Other: Placebo

Stage 1, Day 1, Sequential Cohort 3

Experimental group

Description:

Young and older adult participants will receive VXB-241 240 mcg (medium-high dose) or Placebo, IM, once on Day 1.

Treatment:

Other: Placebo

Biological: VXB-241 240 mcg (Medium-high Dose)

Stage 1, Day 1, Sequential Cohort 4

Experimental group

Description:

Young and older adult participants will receive VXB-241 480 mcg (high dose) or Placebo, IM, once on Day 1.

Treatment:

Biological: VXB-241 480 mcg (High Dose)

Other: Placebo

Stage 2, Day 1, Concurrent Group 1a

Experimental group

Description:

Older adult participants will receive VXB-241 60 mcg (low dose), IM, once on Day 1.

Treatment:

Biological: VXB-241 60 mcg (Low Dose)

Stage 2, Day 1, Concurrent Group 1b

Experimental group

Description:

Older adult participants will receive VXB-241 120 mcg (medium dose), IM, once on Day 1.

Treatment:

Biological: VXB-241 120 mcg (Medium Dose)

Stage 2, Day 1, Concurrent Group 1c

Experimental group

Description:

Older adult participants will receive VXB-241 240 mcg (medium-high dose), IM, once on Day 1.

Treatment:

Biological: VXB-241 240 mcg (Medium-high Dose)

Stage 2, Day 1, Concurrent Group 1d

Experimental group

Description:

Older adult participants will receive VXB-241 480 mcg (high dose), IM, once on Day 1.

Treatment:

Biological: VXB-241 480 mcg (High Dose)

Stage 2, Day 1, Concurrent Group 2a

Active Comparator group

Description:

Older adult participants will receive Arexvy 120 mcg, IM, once on Day 1.

Treatment:

Biological: Arexvy 120 mcg

Stage 2, Day 1, Concurrent Group 3a

Placebo Comparator group

Description:

Older adult participants will receive Placebo, IM, once on Day 1.

Treatment:

Other: Placebo

Group 1e: VXB-241 Revaccination in VXB-241 Recipients

Experimental group

Description:

Approximately 50% of the older adult participants who received VXB-241 (any dose level), will receive VXB-241, IM, once on Day 364 in the second year of the study.

Treatment:

Biological: VXB-241

Group 1f: Placebo Revaccination in VXB-241 Recipients

Placebo Comparator group

Description:

Approximately 50% of the older adult participants who received VXB-241 (any dose level), will receive Placebo, IM, once on Day 364 in the second year of the study.

Treatment:

Other: Placebo

Group 2b: Arexvy Revaccination

Active Comparator group

Description:

All older adult participants who received Arexvy 120 mcg will receive Arexvy 120 mcg revaccination, IM, once on Day 364 in the second year of the study.

Treatment:

Biological: Arexvy 120 mcg

Group 3b: VXB-241

Experimental group

Description:

All older adult participants who received Placebo will receive VXB-241, IM, once on Day 364 in the second year of the study.

Treatment:

Biological: VXB-241