A Dose Reduction Immunobridging and Safety Study of Two HPV Vaccines in Tanzanian Girls

NCT02834637 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: MITU-002
• Study Type: interventional
• Target: 930
• Locations: 1 country
• Sites: 1

Brief Summary

Cervical cancer is the most common cancer in women aged 15-44 years in East Africa, and mortality rates are very high. HPV vaccines are most effective if given to girls who have not yet acquired HPV infection. In Tanzania, HPV vaccine has been shown to be safe, acceptable and can be delivered with high coverage (\~80%). However, the cost of delivering HPV vaccine is considerably higher than costs for traditional infant/child vaccinations. This is primarily because of costs to establish outreach programmes and associated personnel costs including nurses who must spend significant time away from their posts to deliver vaccine, especially if multiple doses are needed. There is global interest in simplifying HPV vaccine delivery by reducing the number of doses. If a single dose could be given, this could halve the costs of delivery, making it more accessible to the populations that need it most. Recently, the WHO recommended that 2 doses of HPV vaccine could be given to young girls, based on studies in high and upper middle-income countries. However in Africa high rates of infections like malaria and worms can affect immune responses to vaccines. It is essential to know that reducing the number of doses does not reduce the protective immune response of these vaccines. The investigators are conducting a trial in Tanzanian girls aged 9-14 years to establish whether a single dose of HPV vaccine produces immune responses that are likely to be effective in preventing cervical cancer. Two different HPV vaccines, the bivalent (2-v) vaccine that protects against HPV 16/18 (the cause of 70% of cancers) and the 9-valent (9-v) vaccine that protects against 9 HPV types, will be compared. The trial will randomise 900 girls to 6 arms and follow them for 36 months. Girls will receive the 2-v or the 9-v HPV vaccine, as 1, 2 or 3 doses. Girls receiving 1 or 2 doses will be compared with those receiving 3 doses of the same vaccine, to ensure that the reduced dose regimen produces an immune response that is not inferior to 3 doses. Girls in the 1 and 2 dose arms will be enrolled in an extension and followed for up to 9 years, to examine the stability of immune responses. The immune responses in this study will also be compared with results from other countries where the vaccine has been shown to be protective. This will provide information about whether a reduced number of doses is likely to be protective in Africa. This work will be extremely important in informing future HPV vaccination strategies and will be one of the first randomised trials of 1 and 2 doses of any HPV vaccine in Africa.

Conditions

Human Papilloma Virus

Keywords

HPV; cervical cancer; vaccines; HPV vaccine; dose reduction; Human papilloma virus vaccine schedules

Outcome Measures

Primary Outcomes (3)

• non-inferiority of antibody seropositivity of 1 dose compared with 2 or 3 doses of the same vaccine

  Proportion with HPV 16/18-specific seropositivity

  Month 24

• non-inferiority of antibody geometric mean titre (GMT) of 1 dose of either vaccine compared with historical cohorts of women who received 1 dose in whom efficacy has been demonstrated

  Geometric mean HPV 16/18 titre

  Month 24

• non-inferiority of antibody seropositivity of 1 dose compared with 2 doses of the same vaccine

  Proportion with HPV 16/18-specific seropositivity

  Month 60 and Month 108

Secondary Outcomes (14)

• non-inferiority of HPV 16/18 seropositivity after 1 dose compared with 2 or 3 doses of the same vaccine

  Month 12 and Month 36

• evaluate HPV 16/18 seropositivity and antibody GMT at all time points when comparing 2 doses with 3 doses of the same vaccine.

  Month 7, Month 12, Month 24 and Month 36

• equivalence of HPV 16/18 seropositivity and antibody GMT at all time points when comparing the same dose regimen between the 2 vaccine types

  Month 12, Month 24, Month 36, Month 60, Month 84 and Month 108

• evaluate HPV 16/18 antibody avidity and memory B cell responses at all time points, comparing different dose regimens of the same vaccine and the same dose regimen between the two vaccines

  Month 12, Month 24, Month 36, Month 84 and Month 108 (avidity); Month 12, Month 24 and Month 36 (memory B cells)

• stability of antibody responses when comparing within the same arm.

  Month 36, Month 60 and M108

Study Arms (6)

3 doses 2valent

ACTIVE COMPARATOR

3 doses of bivalent HPV vaccine (Cervarix) given at M0, M1 and M6

Drug: bivalent HPV vaccine

2 doses 2valent

ACTIVE COMPARATOR

2 doses of bivalent HPV vaccine (Cervarix) given at M0 and M6

Drug: bivalent HPV vaccine

1 dose 2valent

ACTIVE COMPARATOR

1 dose of bivalent HPV vaccine (Cervarix) given at M0

Drug: bivalent HPV vaccine

3 doses 9valent

ACTIVE COMPARATOR

3 doses of nonavalent HPV vaccine (Gardasil9) given at M0, M2 and M6

Drug: nonavalent HPV vaccine

2 doses 9valent

ACTIVE COMPARATOR

2 doses of nonavalent HPV vaccine (Gardasil9) given at M0 and M6

Drug: nonavalent HPV vaccine

1 dose 9valent

ACTIVE COMPARATOR

1 dose of nonavalent HPV vaccine (Gardasil9) given at M0

Drug: nonavalent HPV vaccine

Interventions

bivalent HPV vaccine DRUG

head to head comparisons of different dose schedules and HPV vaccine types

Also known as: Cervarix

1 dose 2valent; 2 doses 2valent; 3 doses 2valent

nonavalent HPV vaccine DRUG

head to head comparisons of different dose schedules and HPV vaccine types

Also known as: Gardasil9

1 dose 9valent; 2 doses 9valent; 3 doses 9valent

Eligibility Criteria

• Age: 9 Years - 14 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Born female;
• Aged between 9 and 14 years inclusive;
• Enrolled in a government primary or secondary day school in Mwanza city (or neighbouring district if included);
• Living in Mwanza city (or neighbouring district if included) without plans to move away in the next 36 months;
• Willing to participate in the study and sign the informed assent form;
• Supported in this study participation by at least one of their parents (or LAR), who has signed the informed consent document;
• In good health as determined by a medical history (a physical examination will be conducted if necessary according to the clinician's judgement); and
• Able to pass a Test of Understanding (TOU) if aged 12 years or above, or if younger than 12 years old, a parent or LAR is able to pass a TOU

You may not qualify if:

• They are diagnosed with chronic conditions, such as autoimmune conditions, degenerative diseases, neurologic or genetic diseases among others;
• They are HIV positive, or immunocompromised;
• They are pregnant, less than three months post-partum or currently breastfeeding;
• They are allergic to one of the vaccine components or to latex;
• They are sexually active and are not willing to use an effective birth control method from 28 days before the first dose until 60 days after the last vaccine dose;
• The nurse or clinician determining the eligibility, in agreement with principal investigator, considers that there is a reason that precludes participation;
• They have been previously vaccinated against HPV

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• University of York: collaborator
• Institut Català d'Oncologia: collaborator
• National Cancer Institute (NCI): collaborator
• Karolinska Institutet: collaborator
• Technische Universität Berlin: collaborator
• Tanzanian National Institute for Medical Research: collaborator
• University of Glasgow: collaborator

Study Sites (1)

Mwanza Intervention Trials Unit (MITU)

Mwanza, Tanzania

Location

Related Publications (7)

• Baisley K, Kemp TJ, Kreimer AR, Basu P, Changalucha J, Hildesheim A, Porras C, Whitworth H, Herrero R, Lacey CJ, Schiller JT, Lucas E, Mutani P, Dillner J, Indangasi J, Muwonge R, Hayes RJ, Pinto LA, Watson-Jones D. Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose of HPV vaccine in historical cohorts: an immunobridging analysis of a randomised controlled trial. Lancet Glob Health. 2022 Oct;10(10):e1485-e1493. doi: 10.1016/S2214-109X(22)00306-0.

  PMID: 36113532 BACKGROUND

• Baisley KJ, Whitworth HS, Changalucha J, Pinto L, Dillner J, Kapiga S, de Sanjose S, Mayaud P, Hayes RJ, Lacey CJ, Watson-Jones D. A dose-reduction HPV vaccine immunobridging trial of two HPV vaccines among adolescent girls in Tanzania (the DoRIS trial) - Study protocol for a randomised controlled trial. Contemp Clin Trials. 2021 Feb;101:106266. doi: 10.1016/j.cct.2021.106266. Epub 2021 Jan 6.

  PMID: 33421649 BACKGROUND

• Watson-Jones D, Changalucha J, Whitworth H, Pinto L, Mutani P, Indangasi J, Kemp T, Hashim R, Kamala B, Wiggins R, Songoro T, Connor N, Mbwanji G, Pavon MA, Lowe B, Mmbando D, Kapiga S, Mayaud P, de SanJose S, Dillner J, Hayes RJ, Lacey CJ, Baisley K. Immunogenicity and safety of one-dose human papillomavirus vaccine compared with two or three doses in Tanzanian girls (DoRIS): an open-label, randomised, non-inferiority trial. Lancet Glob Health. 2022 Oct;10(10):e1473-e1484. doi: 10.1016/S2214-109X(22)00309-6.

  PMID: 36113531 BACKGROUND

• Watson-Jones D, Changalucha J, Maxwell C, Whitworth H, Mutani P, Kemp TJ, Kamala B, Indangasi J, Constantine G, Hashim R, Mwanzalima D, Wiggins R, Mmbando D, Connor N, Pavon MA, Lowe B, Kapiga S, Mayaud P, de Sanjose S, Dillner J, Hayes RJ, Lacey CJ, Pinto L, Baisley K. Durability of immunogenicity at 5 years after a single dose of human papillomavirus vaccine compared with two doses in Tanzanian girls aged 9-14 years: results of the long-term extension of the DoRIS randomised trial. Lancet Glob Health. 2025 Feb;13(2):e319-e328. doi: 10.1016/S2214-109X(24)00477-7.

  PMID: 39890232 BACKGROUND

• Baisley K, Kemp TJ, Mugo NR, Whitworth H, Onono MA, Njoroge B, Indangasi J, Bukusi EA, Prabhu PR, Mutani P, Galloway DA, Mwanzalime D, Kapiga S, Lacey CJ, Hayes RJ, Changalucha J, Pinto LA, Barnabas RV, Watson-Jones D. Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose in young women aged 15-20 years in Kenya (KEN SHE): an immunobridging analysis of randomised controlled trials. Lancet Glob Health. 2024 Mar;12(3):e491-e499. doi: 10.1016/S2214-109X(23)00586-7.

  PMID: 38365419 BACKGROUND

• Kemp TJ, Baisley K, Changalucha J, Indangasi J, Whitworth H, Lacey CJ, Mwanzalima D, Hashim R, Kapiga S, Hayes RJ, Pinto LA, Watson-Jones D. Immunogenicity of one and two doses of Gardasil(R)9 in Tanzanian girls in the DoRIS Trial. NPJ Vaccines. 2025 Dec 19. doi: 10.1038/s41541-025-01344-1. Online ahead of print.

  PMID: 41419735 DERIVED

• Hsiao A, Struckmann V, Stephani V, Mmbando D, Changalucha J, Baisley K, Levin A, Morgan W, Hutubessy R, Watson-Jones D, Whitworth H, Quentin W. Costs of delivering human papillomavirus vaccination using a one- or two-dose strategy in Tanzania. Vaccine. 2023 Jan 9;41(2):372-379. doi: 10.1016/j.vaccine.2022.11.032. Epub 2022 Nov 29.

  PMID: 36460537 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

human papillomavirus vaccine, L1 type 16, 18

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Deborah Watson-Jones, Dr

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2016
• First Posted: July 15, 2016
• Study Start: February 23, 2017
• Primary Completion: January 15, 2020
• Study Completion (Estimated): March 1, 2027
• Last Updated: September 10, 2025

Record last verified: 2025-03

Locations

TA (1)