| Protocol No: | ECCT/18/10/02 | Date of Protocol: | 03-08-2018 |
| Study Title: |
Single-dose HPV catch-up vaccination efficacy: A blinded, randomized study of single-dose HPV vaccination among adolescent girls and young women in Kenya |
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| KENya Single-dose HPV vaccine-Efficacy (KEN SHE) Study | ||
| KENya Single-dose HPV vaccine-Efficacy (KEN SHE) Study
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| Single-dose HPV catch-up vaccination efficacy: A blinded, randomized study of single-dose HPV vaccination among adolescent girls and young women in Kenya | ||
| Study Objectives: | Primary Objectives:
Secondary objectives
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| 4 | Primary Objectives: 1. To test the efficacy of immediate single-dose bivalent or nonavalent HPV vaccination to prevent incident persistent HPV 16/18 infection compared to delayed nonavalent HPV vaccination for young women age 15-20 years. 2. To test the efficacy of immediate single-dose nonavalent HPV vaccination to prevent incident persistent HPV 16/18/31/33/45/52/58 infection compared to delayed nonavalent HPV vaccination for young women age 15-20 years. 3. To determine whether vaccine-type HPV antibody responses after single-dose bivalent or nonavalent vaccination are noninferior in 9-14 year old girls versus 15-20 year old young women. Secondary objectives 1. To assess cost, cost-effectiveness, and budget impact of single-dose HPV vaccination to support implementation strategies for single-dose HPV vaccination following WHO recommendation in high cervical cancer burden settings. 2. To evaluate B-cell markers as a proxy for immune memory following single-dose bivalent and nonavalent vaccination. | |
| 9 | Primary Objectives: 1. To test the efficacy of immediate single-dose bivalent or nonavalent HPV vaccination to prevent incident persistent HPV 16/18 infection compared to delayed HPV vaccination for young women age 15-20 years. 2. To test the efficacy of immediate single-dose nonavalent HPV vaccination to prevent incident persistent HPV 16/18/31/33/45/52/58 infection compared to delayed HPV vaccination for young women age 15-20 years. 3. To assess durability of HPV vaccine efficacy using a blinded crossover vaccination design. Secondary objectives 1. To determine whether vaccine-type HPV antibody responses after single-dose bivalent or nonavalent vaccination are noninferior in 9-14-year-old girls versus 15-20 year old young women. 2. To assess cost, cost-effectiveness, and budget impact of single-dose HPV vaccination to support implementation strategies for single-dose HPV vaccination following WHO recommendation in high cervical cancer burden settings. 3. To evaluate B-cell markers as a proxy for immune memory following single-dose bivalent and nonavalent vaccination. 4. To assess vaccine efficacy with the exclusion of infections detected at month 6, as these may represent prevalent infections not detected at baseline rather than incident infections. 5. To assess the characteristics of CD8+ T cell responses in women with either HPV clearance or persistence and identify targets for therapeutic vaccines | |
| Laymans Summary: | LAY STUDY SUMMARY Cervical cancer is one of the most common type of cancers worldwide. About 90% of all cervical cancers occur among women from low and middle income regions, and eastern Africa has the one of the highest rates of cervical cancer. In Kenya, more than 4,800 women are newly diagnosed with cervical cancer and about 2,500 women die from this condition each year.
Cervical cancer is caused by an infection with Human Papillomavirus, also called HPV. HPV is a common infection that affects 80% of adult women and 65-70% of adult men and is usually transmitted through sexual activities. There are over 100 sub-types of HPV. Of these, 13 types are considered high risk because of their potential to cause cancer. While most HPV infections heal on their own and do not cause any illness, some infections can persist in the body. Persistent infection with a high-risk type of HPV could lead to cancer.
There are vaccines that can prevent high risk HPV infections and, therefore, cervical cancer. These vaccines are highly effective and safe. Currently, Kenyan Ministry of Health and the World Health Organization recommend vaccinating with two doses of the HPV vaccine. In 2019, the Ministry of Health will begin a national program to vaccinate girls in Standard 4. Additionally, catch up vaccination of girls up to age 14 years will be supported by the Global Alliance for Vaccination & Immunization. However, there are currently no plans to vaccinate adolescents aged 15 and older, who are also at risk for HPV infection. The primary challenge to vaccinating this age group is the cost associated with a 2 dose vaccines schedule. Reducing the vaccine dose to one could address this barrier.
The purpose of our study is to learn whether one dose of HPV vaccine is effective in preventing HPV infection in adolescents aged 15-20 years old. Previous studies done in other countries have found that a single dose of HPV vaccine worked just as well as two doses in preventing HPV. Our study will confirm these findings using a gold-standard study design. Several HPV vaccines are available. Our study will determine the efficacy of two HPV vaccines: bivalent and nonavalent vaccines. The bivalent vaccine protects against 2 high risk HPV types and the nonavalent vaccine protects against 7 high risk types and 2 low risk types.
At the start of our study, young women will be randomly sorted into three arms. In arm 1, the women will receive the bivalent HPV vaccine. In arm 2, the women will receive the nonvalent vaccine. And in arm 3, the women will receive a meningococcal vaccine. At the end of the study, those in arms 1 and 2 will receive the meningococcal vaccine, while those in arm 3 will receive either the bivalent or nonavalent HPV vaccine. The three arm study structure makes it possible to compare the women who received an HPV vaccine to those who did not receive an HPV vaccine during the study. We chose to use meningococcal vaccine because it is not ethical to use a placebo when the HPV vaccines have been previously shown to be effective. Additionally, the meningococcal vaccine is already part of the recommended vaccination schedule for adolescents in Kenya. Over the course of the study, the participants will be asked to return for follow up visits periodically. During these visits, the study staff will conduct pelvic and physical exams, and take specimen for HPV testing. Other sexual and reproductive health services will also be offered to the participants during follow up visits. |
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| 4 | LAY STUDY SUMMARY Cervical cancer is one of the most common type of cancers worldwide. About 90% of all cervical cancers occur among women from low and middle income regions, and eastern Africa has the one of the highest rates of cervical cancer. In Kenya, more than 4,800 women are newly diagnosed with cervical cancer and about 2,500 women die from this condition each year. Cervical cancer is caused by an infection with Human Papillomavirus, also called HPV. HPV is a common infection that affects 80% of adult women and 65-70% of adult men and is usually transmitted through sexual activities. There are over 100 sub-types of HPV. Of these, 13 types are considered high risk because of their potential to cause cancer. While most HPV infections heal on their own and do not cause any illness, some infections can persist in the body. Persistent infection with a high-risk type of HPV could lead to cancer. There are vaccines that can prevent high risk HPV infections and, therefore, cervical cancer. These vaccines are highly effective and safe. Currently, Kenyan Ministry of Health and the World Health Organization recommend vaccinating with two doses of the HPV vaccine. In 2019, the Ministry of Health will begin a national program to vaccinate girls in Standard 4. Additionally, catch up vaccination of girls up to age 14 years will be supported by the Global Alliance for Vaccination & Immunization. However, there are currently no plans to vaccinate adolescents aged 15 and older, who are also at risk for HPV infection. The primary challenge to vaccinating this age group is the cost associated with a 2 dose vaccines schedule. Reducing the vaccine dose to one could address this barrier. The purpose of our study is to learn whether one dose of HPV vaccine is effective in preventing HPV infection in adolescents aged 15-20 years old. Previous studies done in other countries have found that a single dose of HPV vaccine worked just as well as two doses in preventing HPV. Our study will confirm these findings using a gold-standard study design. Several HPV vaccines are available. Our study will determine the efficacy of two HPV vaccines: bivalent and nonavalent vaccines. The bivalent vaccine protects against 2 high risk HPV types and the nonavalent vaccine protects against 7 high risk types and 2 low risk types. At the start of our study, young women will be randomly sorted into three arms. In arm 1, the women will receive the bivalent HPV vaccine. In arm 2, the women will receive the nonvalent vaccine. And in arm 3, the women will receive a meningococcal vaccine. At the end of the study, those in arms 1 and 2 will receive the meningococcal vaccine, while those in arm 3 will receive either the bivalent or nonavalent HPV vaccine. The three arm study structure makes it possible to compare the women who received an HPV vaccine to those who did not receive an HPV vaccine during the study. We chose to use meningococcal vaccine because it is not ethical to use a placebo when the HPV vaccines have been previously shown to be effective. Additionally, the meningococcal vaccine is already part of the recommended vaccination schedule for adolescents in Kenya. Over the course of the study, the participants will be asked to return for follow up visits periodically. During these visits, the study staff will conduct pelvic and physical exams, and take specimen for HPV testing. Other sexual and reproductive health services will also be offered to the participants during follow up visits. | |
| 7 | LAY STUDY SUMMARY Cervical cancer is one of the most common type of cancers worldwide. About 90% of all cervical cancers occur among women from low and middle income regions, and eastern Africa has the one of the highest rates of cervical cancer. In Kenya, more than 4,800 women are newly diagnosed with cervical cancer and about 2,500 women die from this condition each year. Cervical cancer is caused by an infection with Human Papillomavirus, also called HPV. HPV is a common infection that affects 80% of adult women and 65-70% of adult men and is usually transmitted through sexual activities. There are over 100 sub-types of HPV. Of these, 13 types are considered high risk because of their potential to cause cancer. While most HPV infections heal on their own and do not cause any illness, some infections can persist in the body. Persistent infection with a high-risk type of HPV could lead to cancer. There are vaccines that can prevent high risk HPV infections and, therefore, cervical cancer. These vaccines are highly effective and safe. Currently, Kenyan Ministry of Health and the World Health Organization recommend vaccinating with two doses of the HPV vaccine. In 2019, the Ministry of Health began a national program to vaccinate girls in Standard 4. Additionally, catch up vaccination of girls up to age 14 years is supported by the Global Alliance for Vaccination & Immunization. However, there are currently no plans to vaccinate adolescents aged 15 and older, who are also at risk for HPV infection. The primary challenge to vaccinating this age group is the cost associated with a 2 dose vaccines schedule. Reducing the vaccine dose to one could address this barrier. The purpose of our study is to learn whether one dose of HPV vaccine is effective in preventing HPV infection in adolescents aged 15-20 years old. Previous studies done in other countries have found that a single dose of HPV vaccine worked just as well as two doses in preventing HPV. Our study will confirm these findings using a gold-standard study design. Several HPV vaccines are available. Our study will determine the efficacy of two HPV vaccines: bivalent and nonavalent vaccines. The bivalent vaccine protects against 2 high risk HPV types and the nonavalent vaccine protects against 7 high risk types and 2 low risk types. At the start of our study, young women will be randomly sorted into three arms. In arm 1, the women will have received the bivalent HPV vaccine. In arm 2, the women will have received the nonvalent vaccine. And in arm 3, the women will haved received a meningococcal vaccine. At crossover vaccination, those in arms 1 and 2 will receive the meningococcal vaccine, while those in arm 3 will receive HPV vaccine. The three arm study structure makes it possible to compare the women who received an HPV vaccine to those who did not receive an HPV vaccine during the study. We chose to use meningococcal vaccine because meningococcal vaccines have clinical benefits and are already part of the recommended vaccination schedule for adolescents in Kenya. Over the course of the study, the participants will be asked to return for follow up visits periodically. During these visits, the study staff will conduct pelvic and physical exams, and take specimen for HPV testing. Other sexual and reproductive health services will also be offered to the participants during follow up visits. The primary analysis has demonstrated high single-dose HPV vaccine efficacy. Based on these results, participants who initially did not receive HPV vaccine will receive HPV vaccination and be followed for 18 months. Participants in the HPV vaccine arms will receive the meningococcal vaccine in a blinded crossover design. Participants will be followed for 18 months following crossover vaccination to match with 18 month primary efficacy period. Thus, we will use the blinded cross-over design to assess the durability of single-dose HPV vaccination. | |
| 8 | Cervical cancer is one of the most common type of cancers worldwide. About 90% of all cervical cancers occur among women from low and middle income regions, and eastern Africa has the one of the highest rates of cervical cancer. In Kenya, more than 4,800 women are newly diagnosed with cervical cancer and about 2,500 women die from this condition each year. Cervical cancer is caused by an infection with Human Papillomavirus, also called HPV. HPV is a common infection that affects 80% of adult women and 65-70% of adult men and is usually transmitted through sexual activities. There are over 100 sub-types of HPV. Of these, 13 types are considered high risk because of their potential to cause cancer. While most HPV infections heal on their own and do not cause any illness, some infections can persist in the body. Persistent infection with a high-risk type of HPV could lead to cancer. There are vaccines that can prevent high risk HPV infections and, therefore, cervical cancer. These vaccines are highly effective and safe. Currently, Kenyan Ministry of Health and the World Health Organization recommend vaccinating with two doses of the HPV vaccine. In 2019, the Ministry of Health began a national program to vaccinate girls in Standard 4. Additionally, catch up vaccination of girls up to age 14 years is supported by the Global Alliance for Vaccination & Immunization. However, there are currently no plans to vaccinate adolescents aged 15 and older, who are also at risk for HPV infection. The primary challenge to vaccinating this age group is the cost associated with a 2 dose vaccines schedule. Reducing the vaccine dose to one could address this barrier. The purpose of our study is to learn whether one dose of HPV vaccine is effective in preventing HPV infection in adolescents aged 15-20 years old. Previous studies done in other countries have found that a single dose of HPV vaccine worked just as well as two doses in preventing HPV. Our study will confirm these findings using a gold-standard study design. Several HPV vaccines are available. Our study will determine the efficacy of two HPV vaccines: bivalent and nonavalent vaccines. The bivalent vaccine protects against 2 high risk HPV types and the nonavalent vaccine protects against 7 high risk types and 2 low risk types. At the start of our study, young women will be randomly sorted into three arms. In arm 1, the women will have received the bivalent HPV vaccine. In arm 2, the women will have received the nonvalent vaccine. And in arm 3, the women will have received a meningococcal vaccine. At crossover vaccination, those in arms 1 and 2 will receive the meningococcal vaccine, while those in arm 3 will receive HPV vaccine. The three arm study structure makes it possible to compare the women who received an HPV vaccine to those who did not receive an HPV vaccine during the study. We chose to use meningococcal vaccine because meningococcal vaccines have clinical benefits and are already part of the recommended vaccination schedule for adolescents in Kenya. Over the course of the study, the participants will be asked to return for follow up visits periodically. During these visits, the study staff will conduct pelvic and physical exams, and take specimen for HPV testing. Other sexual and reproductive health services will also be offered to the participants during follow up visits. The primary analysis has demonstrated high single-dose HPV vaccine efficacy. Based on these results, participants who initially did not receive HPV vaccine will receive HPV vaccination and be followed for 18 months. Participants in the HPV vaccine arms will receive the meningococcal vaccine in a blinded crossover design. Participants will be followed for 18 months following crossover vaccination to match with 18 month primary efficacy period. Thus, we will use the blinded cross-over design to assess the durability of single-dose HPV vaccination. | |
| 9 | Cervical cancer is one of the most common type of cancers worldwide. About 90% of all cervical cancers occur among women from low and middle income regions, and eastern Africa has the one of the highest rates of cervical cancer. In Kenya, more than 4,800 women are newly diagnosed with cervical cancer and about 2,500 women die from this condition each year. Cervical cancer is caused by an infection with Human Papillomavirus, also called HPV. HPV is a common infection that affects 80% of adult women and 65-70% of adult men and is usually transmitted through sexual activities. There are over 100 sub-types of HPV. Of these, 13 types are considered high risk because of their potential to cause cancer. While most HPV infections heal on their own and do not cause any illness, some infections can persist in the body. Persistent infection with a high-risk type of HPV could lead to cancer. There are vaccines that can prevent high risk HPV infections and, therefore, cervical cancer. These vaccines are highly effective and safe. Currently, Kenyan Ministry of Health and the World Health Organization recommend vaccinating with two doses of the HPV vaccine. In 2019, the Ministry of Health began a national program to vaccinate girls in Standard 4. Additionally, catch up vaccination of girls up to age 14 years is supported by the Global Alliance for Vaccination & Immunization. However, there are currently no plans to vaccinate adolescents aged 15 and older, who are also at risk for HPV infection. The primary challenge to vaccinating this age group is the cost associated with a 2 dose vaccines schedule. Reducing the vaccine dose to one could address this barrier. The purpose of our study is to learn whether one dose of HPV vaccine is effective in preventing HPV infection in adolescents aged 15-20 years old. Previous studies done in other countries have found that a single dose of HPV vaccine worked just as well as two doses in preventing HPV. Our study will confirm these findings using a gold-standard study design. Several HPV vaccines are available. Our study will determine the efficacy of two HPV vaccines: bivalent and nonavalent vaccines. The bivalent vaccine protects against 2 high risk HPV types and the nonavalent vaccine protects against 7 high risk types and 2 low risk types. At the start of our study, young women will be randomly sorted into three arms. In arm 1, the women will have received the bivalent HPV vaccine. In arm 2, the women will have received the nonvalent vaccine. And in arm 3, the women will have received a meningococcal vaccine. At crossover vaccination, those in arms 1 and 2 will receive the meningococcal vaccine, while those in arm 3 will receive HPV vaccine. The three arm study structure makes it possible to compare the women who received an HPV vaccine to those who did not receive an HPV vaccine during the study. We chose to use meningococcal vaccine because meningococcal vaccines have clinical benefits and are already part of the recommended vaccination schedule for adolescents in Kenya. Over the course of the study, the participants will be asked to return for follow up visits periodically. During these visits, the study staff may conduct pelvic and physical exams, and take specimen for HPV testing or participant collect self swab for HPV testing. Other sexual and reproductive health services will also be offered to the participants during follow up visits. The primary analysis has demonstrated high single-dose HPV vaccine efficacy. Based on these results, participants who initially did not receive HPV vaccine will receive HPV vaccination and be followed for 18 months. Participants in the HPV vaccine arms will receive the meningococcal vaccine in a blinded crossover design. Participants will be followed for at least 18 months following crossover vaccination to match with 18 month primary efficacy period. Thus, we will use the blinded cross-over design to assess the durability of single-dose HPV vaccination. | |
| Abstract of Study: | Abstract (300 words):Introduction: Cervical cancer is the leading cause of new cancer cases among women in Kenya representing a substantial burden of disease for women. HPV infection is a necessary cause of cervical cancer and preliminary evidence suggests a single-dose of the HPV vaccine would provide efficacy in excess of 95%,1 supporting HPV vaccination as a scaleable intervention for cervical cancer prevention. An evidence gap exists on the efficacy and durability of single-dose HPV vaccine among young women in Africa.
Objectives: The primary objective is to compare immediate, single-dose bivalent (HPV 16/18) and nonavalent (HPV 16/18/31/33/45/52/58/6/11) vaccination (and delayed meningococcal immunization) with delayed HPV vaccination (and immediate meningococcal immunization) among young women age 15-20 years. We will also conduct costing, budget impact, and cost-effectiveness analyses to provide evidence for decision makers
Methods: Women age 15-20 years old will be randomized to immediate bivalent and delayed meningococcal vaccine (arm 1), immediate nonavalent vaccine and delayed meningococcal vaccine (arm 2), or delayed HPV vaccine and immediate meningococcal vaccine (arm 3) with 36 months of follow-up. The primary study endpoint is persistent vaccine type specific HPV infection at months 18 and 36. The quantitative antibody response will be documented at months 1 and 24 to support immunobridging analyses to girls and adolescents for the single-dose bivalent and nonavalent vaccines. Using the data on persistent infections and health economic models, we will assess the impact on cervical cancer incidence.
Anticipated results: Our study will evaluate whether or not single-dose vaccination impacts the incidence of persistent HPV infections. Our health economic modeling results will help policy planners assess the long-term costs, benefits and budget impact of single-dose HPV vaccine delivery, in terms of cervical cancer deaths prevented and the costs saved relative to the two or three dose HPV vaccine schedule.
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| 7 | Abstract (300 words): Introduction: Cervical cancer is the leading cause of new cancer cases among women in Kenya representing a substantial burden of disease for women. HPV infection is a necessary cause of cervical cancer and preliminary evidence suggests a single-dose of the HPV vaccine would provide efficacy in excess of 95%,1 supporting HPV vaccination as a scaleable intervention for cervical cancer prevention. An evidence gap exists on the efficacy and durability of single-dose HPV vaccine among young women in Africa.
Objectives: The primary objective is to compare immediate, single-dose bivalent (HPV 16/18) and nonavalent (HPV 16/18/31/33/45/52/58/6/11) vaccination (and delayed meningococcal immunization) with delayed HPV vaccination (and immediate meningococcal immunization) among young women age 15-20 years. We will also conduct costing, budget impact, and cost-effectiveness analyses to provide evidence for decision makers.
Methods: Women age 15-20 years old will be randomized to immediate bivalent and delayed meningococcal vaccine (arm 1), immediate nonavalent vaccine and delayed meningococcal vaccine (arm 2), or delayed HPV vaccine and immediate meningococcal vaccine (arm 3) with up to 54 months of follow-up. The primary study endpoint is persistent vaccine type specific HPV infection at months 18 and 18 months after blinded crossover vaccination. The quantitative antibody response will be documented at months 1 and 24 to support immunobridging analyses to girls and adolescents for the single-dose bivalent and nonavalent vaccines. Using the data on persistent infections and health economic models, we will assess the impact on cervical cancer incidence.
Anticipated results: Our study will evaluate whether or not single-dose vaccination impacts the incidence of persistent HPV infections. Our health economic modeling results will help policy planners assess the long-term costs, benefits and budget impact of single-dose HPV vaccine delivery, in terms of cervical cancer deaths prevented and the costs saved relative to the two or three dose HPV vaccine schedule.
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| 9 | Introduction: Cervical cancer is the leading cause of new cancer cases among women in Kenya representing a substantial burden of disease for women. HPV infection is a necessary cause of cervical cancer and preliminary evidence suggests a single-dose of the HPV vaccine would provide efficacy in excess of 95%,1 supporting HPV vaccination as a scaleable intervention for cervical cancer prevention. An evidence gap exists on the efficacy and durability of single-dose HPV vaccine among young women in Africa.
Objectives: The primary objective is to compare immediate, single-dose bivalent (HPV 16/18) and nonavalent (HPV 16/18/31/33/45/52/58/6/11) vaccination (and delayed meningococcal immunization) with delayed HPV vaccination (and immediate meningococcal immunization) among young women age 15-20 years. We will also conduct costing, budget impact, and cost-effectiveness analyses to provide evidence for decision makers.
Methods: Women age 15-20 years old will be randomized to immediate bivalent and delayed meningococcal vaccine (arm 1), immediate nonavalent vaccine and delayed meningococcal vaccine (arm 2), or delayed HPV vaccine and immediate meningococcal vaccine (arm 3) with up to 72 months of follow-up. The primary study endpoint is persistent vaccine type specific HPV infection at months 18 and 18 months after blinded crossover vaccination. The quantitative antibody response will be documented at months 1 and 24 to support immunobridging analyses to girls and adolescents for the single-dose bivalent and nonavalent vaccines. Using the data on persistent infections and health economic models, we will assess the impact on cervical cancer incidence.
Anticipated results: Our study will evaluate whether or not single-dose vaccination impacts the incidence of persistent HPV infections. Our health economic modeling results will help policy planners assess the long-term costs, benefits and budget impact of single-dose HPV vaccine delivery, in terms of cervical cancer deaths prevented and the costs saved relative to the two or three dose HPV vaccine schedule.
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