Adding Male Single Dose HPV Vaccination to Female HPV Vaccination in Tanzania

Study Overview
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Brief Summary
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Add-Vacc is an unblinded cluster-randomised trial (CRT) with two arms: (i) the national HPV vaccination programme (girls aged  14 years, control arm) and (ii) the national programme plus single-dose male HPV vaccination given to a multi-year cohort of boys (intervention arm). The CRT will be conducted in 26 communities/clusters (13 per arm) in northern Tanzania. Boys aged 14 to 18 years in the intervention arm will receive one dose of the 4-valent HPV vaccine (Gardasil®) that protects against HPV 6, 11, 16, and 18. Population genital HPV prevalence in 18 to 21-year-olds will be compared between intervention clusters (female and male vaccination) and control clusters (female vaccination only) at 3 years after the intervention. Blood sampling for immune responses and adverse event data collection will be performed in a subset of 200 male subjects in selected intervention clusters.

Official Title
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Adding Male Single Dose HPV Vaccination to Female HPV Vaccination in Tanzania

Conditions
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HPV Infection, Vaccine Preventable Disease

Intervention / Treatment
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* Biological: Gardasil® HPV vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parents and adult male participants (aged 18 years) must sign an ICF and male participants aged less than 18 years must sign an informed assent form (IAF), indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study and to receive HPV vaccination. If the parent or participant cannot read or write, the procedures must be explained and informed consent/assent must be witnessed by a literate third party who is not involved in the conduct of the study. Participants must have been born male, and must be aged 14 to 18 years inclusive at time of vaccination. Participants must be living in an intervention community (cluster). Participants must be willing and able to comply with the protocol requirements. Participants must agree to avoid all non-trial immunisations in the 14 days following vaccination with the trial vaccine, other than emergency vaccinations such as post-exposure rabies or tetanus vaccinations. Participants must be healthy as determined by a medical history. A physical examination will be conducted if necessary according to the clinician's judgement. Exclusion Criteria: Boys will be excluded from HPV vaccination if: They have previously been vaccinated against HPV. They have a history of allergy or anaphylaxis to one or more of the HPV vaccine components, to yeast or to latex. They are enrolled in another vaccine research study that specifically specifies that they must not participate in a study of another vaccine They have been diagnosed with a chronic condition (except HIV, as per the comment above), such as an autoimmune condition, sickle cell disease, degenerative disease, neurologic or genetic disease, among others; There are significant conditions or clinically significant findings for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., it would compromise their safety or well-being).

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Cluster randomised trial with 26 communities (13 per arm)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Male vaccination + national HPV vaccination programme<br>Single dose of the 4-valent HPV vaccine (Gardasil®; Merck & Co.) offered to all eligible boys aged 14 to 18 years in the 13 intervention communities. Girls aged 14 years are offered 2 doses of Gardasil® through the Tanzanian national HPV vaccine programme | Biological: Gardasil® HPV vaccine<br>* Single dose 4-valent HPV vaccine in males. Gardasil®, manufactured by MSD, consists of a licensed prophylactic virus-like particle (VLP) vaccine that protects against 4 HPV genotypes (HPV 6, 11, 16, 18).<br>* Other names: 4-valent HPV vaccine;|
| Active Comparator: National HPV vaccination programme only<br>Girls aged 14 years are offered 2 doses of Gardasil® through the Tanzanian national HPV vaccine programme | Biological: Gardasil® HPV vaccine<br>* Single dose 4-valent HPV vaccine in males. Gardasil®, manufactured by MSD, consists of a licensed prophylactic virus-like particle (VLP) vaccine that protects against 4 HPV genotypes (HPV 6, 11, 16, 18).<br>* Other names: 4-valent HPV vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of adding single-dose male HPV vaccination to the national HPV vaccination programme in girls on population 4-valent HPV genotype prevalence in 18 to 21-year-old females and males | Prevalence of 4-valent vaccine HPV genotype DNA (HPV 6, 11, 16 or 18) in males and females aged 18 to 21 years in intervention clusters and control clusters 36 months post-male vaccination | Month 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity and safety of single dose 4-valent HPV vaccination in boys | Proportion seroconverting to, and geometric mean antibody titres (GMTs) for, HPV vaccine genotypes, and safety and tolerability (local and systemic adverse events), measured in a subset of 200 vaccinated boys | Month 12, 24 and 36 | 
| Impact of female-only vaccination through the national vaccination programme on population HPV prevalence in 18 to 21-year-old males and females | The proportion of females, and of males, aged 18 to 21 years in the control arm with detectable genital 4-valent HPV vaccine genotype DNA at baseline and at M36. | Month 36 | 
| Uptake of dose 1 and coverage of dose 2 in eligible target groups for the national HPV vaccination programme; | The proportion of females aged 16 years who received 1 dose of HPV vaccine (uptake) and who complete 2 doses (coverage) by arm at baseline and M36 | Month 36 | 
| Acceptability of a gender-neutral approach to HPV vaccination | Self-reported acceptability of and barriers to receiving male vaccination by community members and to delivering male HPV vaccination by health care workers (HCW) | Month 24 | 
| Cost-effectiveness of adding a multi-year single dose male HPV vaccination strategy to the national female HPV vaccination programme | Incremental cost-effectiveness ratio for single dose male vaccination plus existing female vaccination programme compared to female vaccination only | Month 36 |