Efficacy, immunogenicity, and safety of the 9vHPV vaccine in adult males 20 to 45 years of age

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

1 Apr 2020 → ongoing

Decision date (initial)

2022-11-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-501974-21-00

EudraCT number

2019-003236-23

WHO UTN

U1111-1275-8682

ClinicalTrials.gov

NCT04199689

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Safety, Efficacy

To demonstrate that a 3-dose regimen of the 9vHPV vaccine will reduce the incidence of HPV16/18/31/33/45/52/58-related oral persistent infection 6 months (± 1-month window) or longer compared with placebo in males 20 to 45 years of age

Secondary objectives 3

1. To demonstrate that a 3-dose regimen of the 9vHPV vaccine will reduce the incidence of HPV 6/11-related oral persistent infection 6 months (± 1-month window) or longer compared with placebo in males 20 to 45 years of age
2. To summarize antibody responses (GMT and seroconversion percentages) to each of HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7
3. To evaluate the safety and tolerability of the 9vHPV vaccine when administered to males 20 to 45 years of age

Conditions and MedDRA coding

Prevention of oral persistent infection caused by any of the human papillomavirus types 16, 18, 31, 33, 45, 52, and 58

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Base Study: Is healthy and is judged to be in good physical health based on medical history and physical examination
2. Base Study: Is male, from 20 years to 45 years of age inclusive, at the time of signing the informed consent
3. Base Study: Has provided written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research
4. Base Study: Agrees to provide study personnel with a primary telephone number as well as an alternate means of contact, if available (such as an alternate telephone number or email) for follow-up purposes
5. Base Study: Can read, understand, and complete the electronic vaccination report card (eVRC)
6. Base Study: Has had at least 1 lifetime sexual partner
7. Extension Study: Participants may continue in the Extension Study if Inclusion Criteria #1 and #4 are still met, and the participants was in either the placebo group in the Base Study or the vaccine group in the Base Study but did not complete the vaccination series
8. Extension Study: Provides documented informed consent

Exclusion criteria 20

1. Base Study: Has a history of human papillomavirus (HPV)-related anal lesion (anal intraepithelial neoplasia or anal cancer) or HPV related head and neck cancer
2. Base Study: Has a history of or clinical evidence at the Day 1 external genital examination of HPV-related external lesion
3. Base Study: Has clinical evidence at the Day 1 external genital examination of gross genital lesion suggesting sexually transmitted disease
4. Base Study: Has a fever (defined as oral temperature ≥100.0°F or ≥37.8°C) within a 24-hour period prior to Day 1 visit.
5. Base Study: Has a history of severe allergic reaction (e.g., swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that required medical intervention
6. Base study: Is allergic to any vaccine component, including aluminum, yeast, or BENZONASE®
7. Base study: Has known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injection
8. Base study: Is currently immunocompromised or has been diagnosed as having congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune condition
9. Base study: Has a history of splenectomy
10. Base Study: Has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate by judgment of investigator.
11. Base Study: Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence at the discretion of the investigator. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems because of alcohol use
12. Base Study: Has received within 12 months prior to enrollment, is receiving, or plans to receive during the study, the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (ARAVA®), TNF-α antagonists, monoclonal antibody therapies (including rituximab [RITUXAN®]), intravenous immunoglobulin (IVIG), anti-lymphocyte sera, or other therapy known to interfere with the immune response. Regarding systemic corticosteroids, a participant will be excluded if he is currently receiving steroid therapy, has recently received such therapy, or has received 2 or more courses of high-dose corticosteroids (≥20 mg/day of prednisone [or equivalent] orally or parenterally) lasting at least 1 week in duration in the year prior. Participants using inhaled, nasal, or topical steroids are considered eligible for the study
13. Base Study: Has received within the 3 months prior to vaccination, is receiving, or plans to receive during the study, any immune globulin product (including RhoGAM™) or blood-derived product other than IVIG
14. Base Study: Has received inactivated or recombinant vaccines within 14 days prior to vaccination or receipt of live vaccines within 21 days prior to vaccination
15. Base Study: Is concurrently enrolled in other clinical studies of investigational agents
16. Base Study: Has previously received a marketed HPV vaccine, or has participated in a clinical trial for any HPV vaccine (receiving either active agent or placebo)
17. Base Study: Has engaged in sexual activity 48 hours prior to vaccination. Sexual activity is defined as: penile penetrative vaginal intercourse with female partner; penile penetrative or receptive anal intercourse with male or female partner; or oral sex involving any contact between participant's mouth with a female partner's vagina, genital or anal area or male partner's penis or genital or anal area. This also includes any contact between participant's partner's mouth with participant's penis, genital or anal area
18. Base Study: Is unlikely to adhere to the study procedures, keep appointments, or is planning to permanently relocate from the area prior to the completion of the study or to leave for an extended period when study visits would need to be scheduled
19. Base Study: Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study
20. Extension Study: Participants must be excluded from the Extension Study if Exclusion Criteria #4, 5, 6, 7, 10, 16, or 18 are met

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of Human Papillomavirus (HPV)16/18/31/33/45/52/58-related 6-month Persistent Oral Infection

Secondary endpoints 8

1. Incidence of HPV 6/11-related 6-month Persistent Oral Infection
2. Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 Antibodies
3. Percentage of Participants Who Seroconvert to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
4. Percentage of Participants with at Least 1 Solicited Injection-site Adverse Event (AE)
5. Percentage of Participants with Elevated Temperature (Fever)
6. Percentage of Participants Who Report at Least 1 Systemic AE
7. Percentage of Participants Who Experience at Least 1 Serious Adverse Event
8. Percentage of Participants Who Experience at Least 1 Serious Vaccine-related AE

Investigational products

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

Test 1

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

Yingmei Tu

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Yingmei Tu

Third parties 7

Locations

6 EU/EEA countries · 23 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

Documents 113 files

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

Application history

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