A clinical study of the V116 vaccine for adults who have an increased risk for invasive pneumococcal disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

17 May 2023 → 16 Feb 2024

Decision date (initial)

2023-04-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-502791-22-01

WHO UTN

U1111-1282-1460

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Prophylaxis

1. To evaluate the safety and tolerability of V116 as assessed by the proportion of participants with adverse events (AEs).
2. To evaluate the serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) postvaccination with V116 (30 days postvaccination [Day 30]) and PCV15 + PPSV23 (30 days postvaccination with the final dose in the regimen [Week 12]) within each vaccination group separately.

Secondary objectives 2

1. To evaluate the serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) postvaccination with V116 (Day 30) and PCV15 + PPSV23 (Week 12) within each vaccination group separately.
2. To evaluate the serotype-specific geometric mean fold rises (GMFRs) and proportions of participants with a ≥4-fold rise from baseline (Day 1) to postvaccination with V116 (Day 30) and from baseline (Day 1) to postvaccination with PCV15 + PPSV23 (Week 12) for both OPA and IgG responses within each vaccination group separately.

Conditions and MedDRA coding

Pneumococcal infection

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Has documented result(s) of ≥1 of the following risk conditions for pneumococcal disease: diabetes mellitus, receiving treatment with ≥1 approved antidiabetic medication, with all Hemoglobin A1c (HbA1c) measurements ≤9% within 6 months before first study vaccination; compensated chronic liver disease; diagnosis of chronic obstructive pulmonary disease (COPD) managed per local guidelines; diagnosis of mild or moderate persistent asthma managed per local guidelines; confirmed diagnosis of chronic heart disease managed per local guidelines; confirmed diagnosis of chronic kidney disease (>3 months duration).
2. Is receiving stable medical management for the risk conditions listed in inclusion criterion 1 for ≥3 months with no anticipated major change in treatment expected for the duration of the study and with ≤1 hospitalization directly related to the risk condition.
3. Is an individual of any sex/gender, from 18 years to 64 years of age inclusive, at the time of providing informed consent.
4. Female is not a participant of childbearing potential (POCBP); or if a POCBP Uses an acceptable contraceptive method or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis); their medical history, menstrual history, and recent sexual activity has been reviewed by the investigator.

Exclusion criteria 20

1. Has a history of active hepatitis.
2. Has a history of diabetic ketoacidosis or 2 or more episodes of severe, symptomatic hypoglycemia within 3 months before first study vaccination (Day 1).
3. Has a history of myocardial infarction, acute coronary syndrome, transient ischemic attack, or ischemic or hemorrhagic stroke within 3 months before first study vaccination (Day 1).
4. Has a history of severe pulmonary hypertension with World Health Organization (WHO) functional class ≥3 or history of Eisenmenger syndrome.
5. Has a history of autoimmune related chronic kidney disease, chronic kidney failure, a reversible cause of kidney disease, nephrotic syndrome, or any ineligible Kidney Disease: Improving Global Outcomes (KDIGO)-recommended stage of glomerular filtration rate (GFR) and Albuminuria.
6. Has a history of invasive pneumococcal disease (IPD) (positive blood culture, positive cerebrospinal fluid culture, or positive culture at another sterile site) or known history of other culture-positive pneumococcal disease within 3 years before first study vaccination (Day 1).
7. Has a known hypersensitivity to any component of V116, PCV15, or PPSV23, including diphtheria toxoid.
8. Has a known or suspected impairment of immunological function including, but not limited to, congenital or acquired immunodeficiency, documented human immunodeficiency virus (HIV) infection, functional or anatomic asplenia, or autoimmune disease.
9. Has a coagulation disorder contraindicating intramuscular (IM) vaccination.
10. Had a recent febrile illness or received antibiotic therapy for any acute illness occurring within 72 hours before receipt of any study vaccine.
11. Has a known malignancy that is progressing or has required active treatment <3 years before randomization.
12. Has planned organ transplantation (heart, liver, lung, kidney, or pancreas) or other planned major surgical procedure during the duration of this study.
13. Has expected survival for <1 year.
14. Has received any prior pneumococcal vaccine or is expected to receive any pneumococcal vaccine during the study outside the protocol.
15. Has received systemic corticosteroids (prednisone equivalent of ≥20 mg/day) for ≥14 consecutive days and has not completed intervention ≥14 days before receipt of study vaccine at Visit 2 (Day 1).
16. Is currently receiving systemic immunosuppressive therapy, including chemotherapeutic agents or other immunotherapies/immunomodulators used to treat cancer or other conditions, and interventions associated with organ or bone marrow transplantation, or autoimmune disease.
17. Has received any non-live vaccine ≤14 days before receipt of any study vaccine or is scheduled to receive any non-live vaccine ≤30 days after receipt of any study vaccine.
18. Has received any live virus vaccine (including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) live virus vaccines) ≤30 days before receipt of any study vaccine or is scheduled to receive any live virus vaccine ≤30 days after receipt of any study vaccine.
19. Has received a blood transfusion or blood products, including immunoglobulin ≤6 months before receipt of any study vaccine or is scheduled to receive a blood transfusion or blood product ≤30 days after receipt of any study vaccine.
20. Is receiving chronic home oxygen therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Percentage of participants with solicited injection-site adverse events (AEs) from Day 1 through Day 5 postvaccination
2. Percentage of participants with solicited systemic AEs from Day 1 through Day 5 postvaccination
3. Percentage of participants with vaccine-related serious adverse events (SAEs) from Day 1 through the duration of participation in the study
4. Serotype-specific OPA GMTs postvaccination with V116 (30 days postvaccination [Day 30]) or PCV15 + PPSV23 (30 days postvaccination with the final dose in the regimen [Week 12])

Secondary endpoints 5

1. Serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) postvaccination with V116 (Day 30) and PCV15 + PPSV23 (Week 12)
2. Serotype-specific geometric mean fold rises (GMFRs) from baseline (Day 1) to postvaccination with V116 (Day 30) and from baseline (Day 1) to postvaccination with PCV15 + PPSV2 (Week 12) for OPA responses
3. Serotype-specific GMFRs from baseline (Day 1) to postvaccination with V116 (Day 30) and from baseline (Day 1) to postvaccination with PCV15 + PPSV23 (Week 12) for IgG responses
4. Serotype-specific proportion of participants with a ≥4-fold rise from baseline (Day 1) to postvaccination with V116 (Day 30) and from baseline (Day 1) to postvaccination with PCV15 + PPSV2 (Week 12) for OPA responses
5. Serotype-specific proportion of participants with a ≥4-fold rise from baseline (Day 1) to postvaccination with V116 (Day 30) and from baseline (Day 1) to postvaccination with PCV15 + PPSV2 (Week 12) for IgG responses

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Jayani Pathirana, Clinical Director

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Jayani Pathirana, Clinical Director

Third parties 6

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications