Ignite Creation Date:
2024-05-06 @ 3:49 PM
Last Modification Date:
2024-10-26 @ 1:58 PM
Study NCT ID:
NCT04778527
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-02-06
First Post:
2021-02-25
Brief Title:
A Crossover Adherence and Acceptability Study Assessing a DPP Capsule for HIV and Pregnancy Prevention
Sponsor:
Population Council
Organization:
Population Council
Study Overview
Official Title:
A Randomized Crossover Study Comparing Adherence Preference Acceptability of a Dual Prevention Pill DPP Capsule Containing PrEP an Oral Contraceptive Versus Two Separate Pills in Women at Risk of HIV in Johannesburg South Africa
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
A randomized crossover study to compare adherence preference and acceptability of an over-encapsulated dual prevention pill DPP capsule containing oral pre-exposure prophylaxis PrEP and a combined oral contraceptive COC versus two separate tablets PrEP and COC among women at risk of HIV and unintended pregnancy in Johannesburg South Africa
Detailed Description:
SOUTH AFRICA We will conduct a randomized open-label parallel group 2-way crossover study among approximately 96 women aged 16-40 years old to compare adherence preference acceptability and safety of a single dual prevention pill DPP containing Truvada and the generic COC Zinnia F Regimen A versus Truvada and Zinnia F taken separately Regimen B All participants must already be using COCs for at least 3 months prior to screening and must plan to continue using them for at least one year We are enrolling women who are already using COCs because we believe they are most likely to be interested in a daily oral MPT Furthermore we would like participants who are already accustomed to COCs so that they can have a clearer sense of how PrEP - whether taken separately or in the DPP - makes them feel
Prior to the commencement of the study the Population Council procured and qualified all study drugs required for the crossover study including bulk pills Truvada and Zinnia F for encapsulation COC pill packs and bottles of Truvada Under the guidance of the Councils clinical and regulatory groups PCI Pharma Rockford IL USA over-encapsulated Truvada and Zinnia F according to Good Manufacturing Practices The over-encapsulated pills were then blister packaged pouched and kitted for distribution to participants
The DPP regimen A consists of a kit containing 4 pouches with a 28-day supply of over-encapsulated pills 21 pink and white capsules will contain Truvada over-encapsulated together with a COC the other 7 capsules corresponding to the 7 placebo days in a COC pill pack will be white and will contain Truvada only The provider counseling manual will emphasize the fact that unlike a COC pill pack where 7 pills are placebo all of the pills in the regimen contain Truvada so it will be important to take them for all 28 days For Regimen B participants will receive a 28-day blister pack of Zinnia F as is currently marketed with 21 active pills and 7 placebo pills Truvada will be dispensed in bottles of 30 pills as is currently marketed Participants will be instructed to take one Truvada tablet and one COC table daily for 28 days
After providing written informed consent or assent with parental consent for 16-17-year-old girls women will be screened for eligibility Participants can be enrolled if they are sexually-active defined as having had penile-vaginal sex with a male 3 months before screening currently using a COC that was started 3 months before screening HIV-negative based on HIV rapid test at screening not-pregnant based on hCG urine test at screening have no contraindications for PrEP or COCs and are in good health based on medical history and vital signs PrEP screening will follow the standard of care in South Africa which recommends testing for Hepatitis B blood creatinine levels pregnancy and STIs Women who test positive for pregnancy or HIV will be referred per the local standard of care Participants who test positive for a curable STI will be treated and enrolled Participants who are eligible will be scheduled for an enrollment visit on Day 0 of their menstrual cycle
At enrollment women will be randomly assigned to one of two sequences of the two regimens with all women using both regimens by the end of the crossover study The Population Council study biostatistician created the randomization scheme using Statistical Analysis Software SASSTAT version 94 SAS Institute Inc Cary North Carolina with a 11 allocation using permutated block sizes Randomization is in blocks of 12 with 6 participants assigned to each sequence in each of 8 blocks Half of the women will be assigned to Sequence 1 which is Regimen A followed by Regimen B and the other half will be assigned to Sequence 2 which is Regimen B followed by Regimen A Participants will use each regimen for 3 28-day menstrual cycles and will then switch to the second regimen at their crossover visit At the end of the crossover period participants will be offered a choice of Regimen A or Regimen B or neither to use for up to an additional 6 months
Participants will attend a total of up to 14 clinic visits including Screening Enrollment and monthly follow up visits for up to 12 months No wash-out period is required between regimens At Visit 1 prior to initiating product use participants will be asked to complete a baseline behavioral interview and will be asked which regimen they think they will prefer At all other visits participants will complete behavioral interviews approximately 30 minutes about adherence and acceptability All behavioral interviews will be conducted using computer assisted self-interviewing CASI which has been shown to elicit more truthful reporting than face-to-face interviewing At the end of the Crossover period participants will complete their final CASI interview in which they will be asked to 1 state their preference for the DPP or 2 separate pills 2 to qualify the strength of their preference on a scale of 1-10 and 3 to respond to questions about why they selected one regimen over the other or not A subset of participants who complete the study and anyone who withdraws early will be asked to take part in an in-depth interview to explore qualitatively reasons for continuation and discontinuation as well as the influence of partners family support structures side effects provider interactions and other factors on cMPT choice and adherence
At all follow up visits women will be tested for HIV and pregnancy report adverse events AEs and have a clinical exam if necessary and respond to a structured questionnaire via computer assisted self-interview CASI with questions about acceptability preference and adherence At the end of the Crossover period women will be asked to state which regimen they prefer Accrual is estimated to take approximately 17 months from first participant enrolling to last participant completing the study We will assess and compare PrEP acceptability and adherence by regimen and overall and we will investigate if specific socio-ecological factors eg individual- partner- family- and clinic-level are associated with adherence and acceptability We will also explore facilitators and barriers to use by conducting in-depth interviews with a subset of willing participants who complete the study and any women who withdraws early Furthermore because we assume people are predisposed to judge a specific regimen or technology based on initial impressions we will assess if pre-use preferences are associated with actual experiences and preferences after using each regimen
At each visit women will be tested for pregnancy and HIV and will provide a blood sample for DBS to assess drug levelsadherence to PrEP Adverse events will be recorded during the study although no pharmacokinetic interactions are expected because there are no drug-drug interactions between the reverse transcriptase inhibitors tenofovir and emtricitabine and the contraceptive hormones levonorgestrel and ethinyl estradiol In addition the side effects profiles of the two products are similar the most commonly reported side-effects for both Truvada and COCs are headache and nausea Since we are recruiting women who are already using COCs participants will already be accustomed to side-effects of COCs Participants will be encouraged to contact or visit the clinic with questions or concerns between visits
Rapid HIV testing will be done at screening in accordance with local guidelines Pregnancy will be tested based on hCG levels in urine DBS collected from enrolled participants will be sent to the University of Cape Town where tenofovir disoproxil fumarate TDF drug levels will be measured to evaluate adherence based on expected levels for daily use
Quantitative and qualitative behavioral collection instruments will adhere to our theoretical framework for assessing acceptability with questions adapted from previous HIV-prevention studies as relevant In-depth interview guides will be developed from instruments used in previous PrEP introduction studies and tailored for this study
Quantitative data from the CASI behavioral interviews will be saved at the site in csv comma separated value format and shared with Population Council weekly via encrypted zip files Clinical data collected from participants including background demographics medical and pregnancy history vital signs concomitant medications AEs enrollment and termination dates and records of returned unused pills will be entered into REDCap an electronic data system Data from CASI interviews eCRFs and DBS analysis will be formatted into SAS data sets for analysis Descriptive statistics frequencies mean standard deviation range will be used to summarize data collected and to characterize differences in participants assigned to each Sequence Modeling will be used to assess the impact of background characteristics on adherence preference and acceptability
PC conducted site initiation and training for the crossover study in collaboration with Wits RHI which has extensive experience implementing qualitative and quantitative HIV prevention research studies The Population Council and site coordinator have weekly teleconferences and the full teams are meeting monthly during data collection to discuss and resolve any issues as they occur The PC clinical research associate will make periodic monitoring trips during data collection to ensure the safety of participants and adherence to the protocol The PC team will also review data collected on a weekly basis
Prior to the commencement of the study the Population Council procured and qualified all study drugs required for the crossover study including bulk pills Truvada and Zinnia F for encapsulation COC pill packs and bottles of Truvada Under the guidance of the Councils clinical and regulatory groups PCI Pharma Rockford IL USA over-encapsulated Truvada and Zinnia F according to Good Manufacturing Practices The over-encapsulated pills were then blister packaged pouched and kitted for distribution to participants
The DPP regimen A consists of a kit containing 4 pouches with a 28-day supply of over-encapsulated pills 21 pink and white capsules will contain Truvada over-encapsulated together with a COC the other 7 capsules corresponding to the 7 placebo days in a COC pill pack will be white and will contain Truvada only The provider counseling manual will emphasize the fact that unlike a COC pill pack where 7 pills are placebo all of the pills in the regimen contain Truvada so it will be important to take them for all 28 days For Regimen B participants will receive a 28-day blister pack of Zinnia F as is currently marketed with 21 active pills and 7 placebo pills Truvada will be dispensed in bottles of 30 pills as is currently marketed Participants will be instructed to take one Truvada tablet and one COC table daily for 28 days
After providing written informed consent or assent with parental consent for 16-17-year-old girls women will be screened for eligibility Participants can be enrolled if they are sexually-active defined as having had penile-vaginal sex with a male 3 months before screening currently using a COC that was started 3 months before screening HIV-negative based on HIV rapid test at screening not-pregnant based on hCG urine test at screening have no contraindications for PrEP or COCs and are in good health based on medical history and vital signs PrEP screening will follow the standard of care in South Africa which recommends testing for Hepatitis B blood creatinine levels pregnancy and STIs Women who test positive for pregnancy or HIV will be referred per the local standard of care Participants who test positive for a curable STI will be treated and enrolled Participants who are eligible will be scheduled for an enrollment visit on Day 0 of their menstrual cycle
At enrollment women will be randomly assigned to one of two sequences of the two regimens with all women using both regimens by the end of the crossover study The Population Council study biostatistician created the randomization scheme using Statistical Analysis Software SASSTAT version 94 SAS Institute Inc Cary North Carolina with a 11 allocation using permutated block sizes Randomization is in blocks of 12 with 6 participants assigned to each sequence in each of 8 blocks Half of the women will be assigned to Sequence 1 which is Regimen A followed by Regimen B and the other half will be assigned to Sequence 2 which is Regimen B followed by Regimen A Participants will use each regimen for 3 28-day menstrual cycles and will then switch to the second regimen at their crossover visit At the end of the crossover period participants will be offered a choice of Regimen A or Regimen B or neither to use for up to an additional 6 months
Participants will attend a total of up to 14 clinic visits including Screening Enrollment and monthly follow up visits for up to 12 months No wash-out period is required between regimens At Visit 1 prior to initiating product use participants will be asked to complete a baseline behavioral interview and will be asked which regimen they think they will prefer At all other visits participants will complete behavioral interviews approximately 30 minutes about adherence and acceptability All behavioral interviews will be conducted using computer assisted self-interviewing CASI which has been shown to elicit more truthful reporting than face-to-face interviewing At the end of the Crossover period participants will complete their final CASI interview in which they will be asked to 1 state their preference for the DPP or 2 separate pills 2 to qualify the strength of their preference on a scale of 1-10 and 3 to respond to questions about why they selected one regimen over the other or not A subset of participants who complete the study and anyone who withdraws early will be asked to take part in an in-depth interview to explore qualitatively reasons for continuation and discontinuation as well as the influence of partners family support structures side effects provider interactions and other factors on cMPT choice and adherence
At all follow up visits women will be tested for HIV and pregnancy report adverse events AEs and have a clinical exam if necessary and respond to a structured questionnaire via computer assisted self-interview CASI with questions about acceptability preference and adherence At the end of the Crossover period women will be asked to state which regimen they prefer Accrual is estimated to take approximately 17 months from first participant enrolling to last participant completing the study We will assess and compare PrEP acceptability and adherence by regimen and overall and we will investigate if specific socio-ecological factors eg individual- partner- family- and clinic-level are associated with adherence and acceptability We will also explore facilitators and barriers to use by conducting in-depth interviews with a subset of willing participants who complete the study and any women who withdraws early Furthermore because we assume people are predisposed to judge a specific regimen or technology based on initial impressions we will assess if pre-use preferences are associated with actual experiences and preferences after using each regimen
At each visit women will be tested for pregnancy and HIV and will provide a blood sample for DBS to assess drug levelsadherence to PrEP Adverse events will be recorded during the study although no pharmacokinetic interactions are expected because there are no drug-drug interactions between the reverse transcriptase inhibitors tenofovir and emtricitabine and the contraceptive hormones levonorgestrel and ethinyl estradiol In addition the side effects profiles of the two products are similar the most commonly reported side-effects for both Truvada and COCs are headache and nausea Since we are recruiting women who are already using COCs participants will already be accustomed to side-effects of COCs Participants will be encouraged to contact or visit the clinic with questions or concerns between visits
Rapid HIV testing will be done at screening in accordance with local guidelines Pregnancy will be tested based on hCG levels in urine DBS collected from enrolled participants will be sent to the University of Cape Town where tenofovir disoproxil fumarate TDF drug levels will be measured to evaluate adherence based on expected levels for daily use
Quantitative and qualitative behavioral collection instruments will adhere to our theoretical framework for assessing acceptability with questions adapted from previous HIV-prevention studies as relevant In-depth interview guides will be developed from instruments used in previous PrEP introduction studies and tailored for this study
Quantitative data from the CASI behavioral interviews will be saved at the site in csv comma separated value format and shared with Population Council weekly via encrypted zip files Clinical data collected from participants including background demographics medical and pregnancy history vital signs concomitant medications AEs enrollment and termination dates and records of returned unused pills will be entered into REDCap an electronic data system Data from CASI interviews eCRFs and DBS analysis will be formatted into SAS data sets for analysis Descriptive statistics frequencies mean standard deviation range will be used to summarize data collected and to characterize differences in participants assigned to each Sequence Modeling will be used to assess the impact of background characteristics on adherence preference and acceptability
PC conducted site initiation and training for the crossover study in collaboration with Wits RHI which has extensive experience implementing qualitative and quantitative HIV prevention research studies The Population Council and site coordinator have weekly teleconferences and the full teams are meeting monthly during data collection to discuss and resolve any issues as they occur The PC clinical research associate will make periodic monitoring trips during data collection to ensure the safety of participants and adherence to the protocol The PC team will also review data collected on a weekly basis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None