Human Immunodeficiency Virus
Conditions
Brief summary
HIV Open-label Prevention Extension (HOPE).
Detailed description
A Phase 3B Open-Label Follow-on Trial to Assess the Continues Safety of and Adherence to a Vaginal ring Containing Dapivirine in Women
Interventions
COMBINATION_PRODUCTDapivirine Vaginal Ring
Dapivirine Vaginal Ring, 25 ring given monthly for at least one year.
Sponsors
International Partnership for Microbicides, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Participants will receive a silicone elastomer vaginal matrix ring containing 25 mg of dapivirine to be replaced each month for a total period of 12 months of use.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
Women must meet all of the following criteria to be eligible for inclusion in the study 1. Previously enrolled in MTN-020 (ASPIRE) 2. Able and willing to provide written informed consent to be screened for and to take part in the study 3. Able and willing to provide adequate locator information, as defined in site SOPs 4. HIV-uninfected based on testing performed by study staff at Screening and Enrollment 5. Using an effective method of contraception at Enrollment, and intending to use an effective method for the duration of study participation; effective methods include hormonal methods (except contraceptive ring); intrauterine contraceptive device (IUCD); and sterilization (of participant, as defined in site SOPs) 6. At Screening and Enrollment, agrees not to participate in other research studies involving drugs, medical devices, vaginal products, or vaccines for the duration of study participation
Exclusion criteria
Women who meet any of the following criteria will be excluded from the study 1. Study product use permanently discontinued in response to an AE or safety related concern while taking part in the MTN-020 (ASPIRE) trial 2. Per participant report at Screening: 1. Plans to relocate away from the study site during study participation 2. Plans to travel away from the study site for more than three consecutive months during study participation 3. Per participant report at Enrollment, currently taking Post-Exposure Prophylaxis (PEP) 4. With the exception of MTN-020 (ASPIRE), participation in any other research study involving drugs, medical devices, vaginal products, or vaccines, within 60 days of enrollment 5. Is pregnant at Screening/Enrollment or planning to become pregnant in the participant's anticipated study participation period 6. Currently breastfeeding 7. Diagnosed with urinary tract infection (UTI), pelvic inflammatory disease (PID), STI or reproductive tract infection (RTI) requiring treatment per WHO guidelines 8. At Screening, has a clinically apparent Grade 3 pelvic exam finding (observed by study staff) as per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009), Addendum 1-Female Genital Grading Table for Use in Microbicide Studies 9. Has any of the following laboratory abnormalities at Screening Visit: 1. Aspartate aminotransferase (AST) or alanine transaminase (ALT) \> Grade 3\* 2. Creatinine \> Grade 3\* 3. Hemoglobin \> Grade 3\* 4. Platelet count \> Grade 3\* 5. Pap result ≥ Grade 3 according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 1.0, December 2004 (Clarification dated August 2009) 10. Has any significant medical condition or other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Safety Profile Associated With the Open-label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women | 13 months | Number of participants Grade 2, Grade 3, and all serious Adverse Events. |
| Adherence to the Open Label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women | 13 months | By measuring the residual levels of dapivirine in returned used vaginal rings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of HIV-1 Infection | 13 months | HIV-1 infection as measured by the protocol algorithm |
| Number of Participant Who Acquired HIV-1 With HIV-1 Drug Resistance Associated Mutations. | 13 months | HIV-1 drug resistance mutations among participants who acquire HIV-1, as measured by standard genotype analysis and more sensitive methods to detect low frequency drug-resistant variants |
Countries
Malawi, South Africa, Uganda, Zimbabwe
Participant flow
Recruitment details
MTN-025 was implemented as a follow-on trial to MTN-020, and the inclusion and exclusion criteria were used to ensure the appropriate selection of trial participants for MTN-025. The Decliner Population were former MTN-020 participants who declined participation in the main MTN-025 trial, and who met the inclusion and exclusion criteria Women in the Decliner Population were invited to complete a single visit which consisted of behavioral assessments.
Pre-assignment details
Participants were recruited from RC cohorts of MTN-020 participants. Efforts were made by RCs to maintain contact with MTN-020 (ASPIRE) participants between the end of follow-up in MTN-020 and the initiation of the MTN-025 trial (HOPE) to provide MTN-020 trial results and information regarding the HOPE trial to participants.
Participants by arm
| Arm | Count |
|---|---|
| HIV Open-label Prevention Following demonstration of safety and efficacy of the dapivirine vaginal ring in MTN-020, eligible MTN-020 participants will be offered enrollment into MTN-025, a trial designed to obtain additional safety and adherence data in women
MTN-020:NCT01617096 MTN-025: NCT02858037
Dapivirine Vaginal Ring: Dapivirine Vaginal Ring, 25 ring given monthly for at least one year. | 1,456 |
| Total | 1,456 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Other | 4 |
| Overall Study | Participant Relocated, no follow-up planned | 26 |
| Overall Study | Withdrawal by Subject | 18 |
Baseline characteristics
| Characteristic | HIV Open-label Prevention |
|---|---|
| Age, Continuous | 32.0 Years STANDARD_DEVIATION 6.51 |
| Marital Status Married | 686 Participants |
| Marital Status Not Married | 770 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants |
| Race (NIH/OMB) Black or African American | 1276 Participants |
| Race (NIH/OMB) More than one race | 88 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 84 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Malawi | 157 participants |
| Region of Enrollment South Africa | 705 participants |
| Region of Enrollment Uganda | 172 participants |
| Region of Enrollment Zimbabwe | 422 participants |
| Sex: Female, Male Female | 1456 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 1,368 |
| other Total, other adverse events | 844 / 1,368 |
| serious Total, serious adverse events | 19 / 1,368 |
Outcome results
Primary
Adherence to the Open Label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women
By measuring the residual levels of dapivirine in returned used vaginal rings.
Time frame: 13 months
Population: Exposed Human Immunodeficiency Virus Incidence and Adherence Cohort
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| HIV Open-label Prevention | Adherence to the Open Label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women | Enrollment | 21.0 mg |
| HIV Open-label Prevention | Adherence to the Open Label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women | Month 1 | 21.1 mg |
| HIV Open-label Prevention | Adherence to the Open Label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women | Month 2 | 21.0 mg |
| HIV Open-label Prevention | Adherence to the Open Label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women | Month 3 | 21.1 mg |
| HIV Open-label Prevention | Adherence to the Open Label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women | Month 6 | 21.2 mg |
| HIV Open-label Prevention | Adherence to the Open Label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women | Month 9 | 21.3 mg |
Primary
The Safety Profile Associated With the Open-label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women
Number of participants Grade 2, Grade 3, and all serious Adverse Events.
Time frame: 13 months
Population: Exposed Primary Cohort - included all participants enrolled in the Main Trial Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HIV Open-label Prevention | The Safety Profile Associated With the Open-label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women | At least one Grade 3 or higher AE | 52 Participants |
| HIV Open-label Prevention | The Safety Profile Associated With the Open-label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women | At least one serious AE | 19 Participants |
| HIV Open-label Prevention | The Safety Profile Associated With the Open-label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women | At least one grade 2 or higher related AE | 2 Participants |
Secondary
Incidence of HIV-1 Infection
HIV-1 infection as measured by the protocol algorithm
Time frame: 13 months
Population: Exposed Human Immunodeficiency Virus Incidence and Adherence Cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIV Open-label Prevention | Incidence of HIV-1 Infection | 2.7 events per 100 person-years |
Secondary
Number of Participant Who Acquired HIV-1 With HIV-1 Drug Resistance Associated Mutations.
HIV-1 drug resistance mutations among participants who acquire HIV-1, as measured by standard genotype analysis and more sensitive methods to detect low frequency drug-resistant variants
Time frame: 13 months
Population: Virology Population - included all HIV-1 infected participants in the Exposed HIV Incidence and Adherence Cohort.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HIV Open-label Prevention | Number of Participant Who Acquired HIV-1 With HIV-1 Drug Resistance Associated Mutations. | 6 Participants |