HIV InfectionsPhase 1NCT02419456

Pharmacokinetics of Two Intravaginal Rings (IVRs) Containing Different Dose Strengths of Vicriviroc (MK-4176) and MK-2048

A Phase 1 study testing MK-2048A IVR (Low Dose) and MK-2048A IVR (Original Dose) in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Intravaginal rings (IVRs) may offer an ideal way to deliver antiretroviral (ARV) drugs to prevent HIV infection. This study will evaluate the pharmacokinetics and safety of two IVRs containing different doses of a combination of two HIV ARV drugs, vicriviroc (VCV) (MK-4176) and MK-2048, in healthy, HIV-uninfected… Read more about this study

Who is it for?: Ages 18 to 45 years, women onlyHealthy volunteers can take part
Conditions the study is for: HIV Infections
What is being tested?: MK-2048A IVR (Low Dose) and MK-2048A IVR (Original Dose)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 19 participants
Where: 1 siteUnited States
Study dates: Jun 2015to Mar 2016
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

Born female. Note: Participants who were female at birth, who now identify as male, will not be excluded so long as they are not on female-to-male transition therapy.
Age 18 through 45 years (inclusive) at screening, verified per site SOPs (standard operating procedures)
Able and willing to provide written informed consent to be screened for and take part in this study (MTN-028)
Able and willing to provide adequate locator information, as defined by the site SOPs
HIV-uninfected, based on testing performed by study staff at screening and enrollment (per applicable algorithm in Appendix II of the protocol) and willing to receive results
In general good health at screening and enrollment, as determined by the site Investigator of Record (IoR) or designee

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At screening, participant states willingness to abstain from receptive sexual activity (including penile-vaginal intercourse, anal intercourse, receptive oral intercourse, finger stimulation, and the use of sex toys) for the 5 days prior to the enrollment visit and for the duration of study participation
Per participant report, using an effective method of contraception at enrollment, and intending to continue the use of an effective method for the duration of study participation. Effective methods for MTN-028 include: hormonal methods (except contraceptive IVRs), intrauterine device (IUD) inserted at least 28 days prior to enrollment, engages in sex exclusively with women, sterilized (self or partner), and/or sexually abstinent for the past 90 days
Women over the age of 21 (inclusive) must have documentation of a satisfactory Pap within the past 3 years prior to enrollment consistent with Grade 0 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), or satisfactory evaluation with no treatment required of Grade 1 or higher Pap result. If otherwise eligible women do not have documentation of a recent Pap test, one may be performed at the screening visit.
Per participant report at screening and enrollment, agrees not to participate in other research studies involving drugs, medical devices, or vaginal products for the duration of study participation
Per participant report at screening, regular menstrual cycles with at least 21 days between menses. Note: This criterion is not applicable to participants who report using a progestin-only method of contraception at screening (e.g., Depo-Provera or levonorgestrel-releasing IUD) nor to participants using continuous combination oral contraceptive pills, as the absence of regular menstrual cycles is an expected, normal consequence in this context.
At screening, participant states a willingness to refrain from inserting any non-study vaginal products or objects into the vagina, including but not limited to, spermicides, female condoms, diaphragms, contraceptive IVRs, vaginal medications, menstrual cups, cervical caps (or any other vaginal barrier method), douches, lubricants, sex toys (vibrators, dildos, etc.) for the 5 days prior to enrollment and for the duration of their study participation

Who cannot join

Participant report of any of the following at screening or enrollment:
History of adverse reactions to any of the components of the study products
Non-therapeutic injection drug use in the 12 months prior to screening and enrollment
Post-exposure prophylaxis (PEP) for HIV exposure within 6 months prior to enrollment
Pre-exposure prophylaxis (PrEP) for HIV prevention within the 6 months prior to enrollment
Regular use and/or anticipated regular use during the period of study participation of CYP3A inducer(s) and/or inhibitor(s)

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Use and/or anticipated use during the period of study participation of female-to-male transition therapy
Chronic and/or recurrent candidiasis
Gonorrhea, chlamydia and/or syphilis diagnosis in the 6 months prior to enrollment
Last pregnancy outcome 90 days or less prior to screening
Currently breastfeeding
Has had a hysterectomy
Intends to become pregnant within the next 3 months
Has plans to relocate away from the study site area in the next 3 months
Current sexual partner is known to be HIV-positive at screening or enrollment
Reports participating in any other research study involving drugs, medical devices, or vaginal products within 60 days or less prior to enrollment
At screening or enrollment, as determined by the IoR/designee, any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease
Has any of the following laboratory abnormalities at screening:
Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher
Calculated creatinine clearance less than 60 mL/min by the Cockcroft-Gault formula, where creatinine clearance (female) in mL/min = (140 - age in years) x (weight in kg) x (0.85)/72 x (creatinine in mg/dL)
Hemoglobin Grade 1 or higher
Platelet count Grade 1 or higher
White blood count Grade 2 or higher
Positive hepatitis B surface antigen (HBsAg) test result
Positive anti-hepatitis C virus (HCV) test result
International normalized ratio (INR) greater than 1.5 × the site laboratory upper limit of normal (ULN)
Note: Otherwise eligible participants with an exclusionary test result (other than HIV, hepatitis B virus [HBV], or HCV) can be re-tested during the screening process. If a participant is re-tested and a non-exclusionary result is documented within 45 days of providing informed consent for screening, the participant may be enrolled.
Pregnant at either screening or enrollment. Note: A documented negative pregnancy test performed by study staff is required for inclusion; however a self-reported pregnancy is adequate for exclusion from screening/enrollment into the study.
Diagnosed with urinary tract infection (UTI) at screening or enrollment. Note: Otherwise eligible participants diagnosed with UTI during screening will be offered treatment. If within the 45 day screening window treatment is complete and symptoms have resolved the participant may be enrolled.
Diagnosed with pelvic inflammatory disease, reproductive tract infection (RTI) or a sexually transmitted infection (STI) requiring treatment per current Centers for Disease Control and Prevention (CDC) guidelines (http://www.cdc.gov/std/treatment/) at screening or enrollment. Note: With the exception of gonorrhea, chlamydia and/or syphilis, otherwise eligible participants diagnosed with a RTI during screening will be offered treatment. If within the 45 day screening window treatment is complete and symptoms have resolved, the participant may be enrolled.
At enrollment, has a clinically apparent Grade 1 or higher pelvic exam finding (observed by study clinician or designee) 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. Note: Cervical friability bleeding associated with speculum insertion and/or specimen collection judged to be within the range of normal according to the clinical judgment of the IoR/designee is considered expected non-menstrual bleeding and is not exclusionary.
At screening, severe pelvic relaxation such that either the vaginal walls or the uterine cervix descend beyond the vaginal introitus with valsalva maneuver or has pelvic anatomy that compromises the ability to adequately assess vaginal safety
Has any 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 study objectives

Trial locations and contacts

1 site in 1 country.

United States1 site

Bridge HIV CRS
San Francisco, California, 94143

Other trials in United States

About this study

Official title: Phase 1 Pharmacokinetic Trial of Two Intravaginal Rings (IVRs) Containing Different Dose Strengths of Vicriviroc (MK-4176) and MK-2048

Read the detailed description

The development of safe and effective HIV prevention strategies remains a global health priority. IVRs are currently being studied as a method to deliver HIV ARV drugs in women. This study will evaluate the pharmacokinetics and safety of two IVRs containing different doses of a combination of two HIV ARV drugs, vicriviroc (VCV) (MK-4176) and MK-2048, in healthy, HIV-uninfected women.

This study will enroll healthy, HIV-uninfected women, 18 to 45 years old. Participants will be randomly assigned to receive either the low dose MK-2048A IVR or the original dose MK-2048A IVR. Participants will receive their assigned IVR at the enrollment visit, and the IVR will be removed on Day 28. Participants will attend study visits at screening, enrollment (Day 0), and Days 1, 2, 3, 7, 14, 21, 28, 29, 30, 31, and 35. Study visits may include medical history reviews, physical examinations, blood collection, pelvic specimen collection, urine collection, and counseling and adherence assessments.

Conditions: HIV Infections
Being tested: MK-2048A IVR (Low Dose), MK-2048A IVR (Original Dose)
Medical subject headings: HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MK-2048A IVR (Low Dose)Drug
Contains 91 mg of vicriviroc (MK-4176) and 10 mg of MK-2048.
MK-2048A IVR (Original Dose)Drug
Contains 182 mg of vicriviroc (MK-4176) and 30 mg of MK-2048.

Study groups in NCT02419456
Study group	Role	What they receive
MK-2048A Intravaginal Ring (IVR) (Low Dose)	Experimental	The MK-2048A IVR (Low Dose) will be inserted during the enrollment visit (Day 0), and it will be removed on Day 28. Receives: Drug: MK-2048A IVR (Low Dose)
MK-2048A IVR (Original Dose)	Experimental	The MK-2048A IVR (Original Dose) will be inserted during the enrollment visit (Day 0), and it will be removed on Day 28. Receives: Drug: MK-2048A IVR (Original Dose)

What is being measured

The primary outcome is the main question the study is designed to answer.

Assessment of vaginal fluid concentrations of MK-4176 and MK-2048 during and after IVR use
Measured: Measured through Day 35
Assessment of blood plasma concentrations of MK-4176 and MK-2048 during and after IVR use
Measured: Measured through Day 35
Assessment of cervical tissue concentrations of MK-4176 and MK-2048 during and after IVR use
Measured: Measured through Day 35
Number of genitourinary events Grade 1 or higher judged to be related to study product
As defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Dec 2004 (Clarification dated August 2009), Addendum 1, (Female Genital Grading Table for Use in Microbicide Studies)
Measured: Measured through Day 35
Number of adverse events Grade 2 or higher
As defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Dec 2004 (Clarification dated August 2009)
Measured: Measured through Day 35

Secondary outcomes (1)

Measurement of residual drug levels in IVRs
Measured: Measured through Day 35

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2015Mar 2016

First posted17 Apr 2015 (estimated)
Study startJun 2015
Primary completionMar 2016
Study completionMar 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIV InfectionsStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Participant
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02419456
Sponsor's protocol ID: MTN-028
Other IDs: 12022
Status last verified: May 2016
First submitted: 14 Apr 2015
Last updated: 11 Nov 2021
Results posted: No
Data monitoring committee: Yes

Publications

Liu AY, Zhang J, Anderson PL, Wagner T, Pan Z, Peda M, Gomez K, Beamer M, Jacobson C, Strizki J, Dezzutti CS, Piper JM; MTN-028 Protocol Team for the Microbicide Trials Network. Phase 1 Pharmacokinetic Trial of 2 Intravaginal Rings Containing Different Dose Strengths of Vicriviroc (MK-4176) and MK-2048. Clin Infect Dis. 2019 Mar 19;68(7):1129-1135. doi: 10.1093/cid/ciy652.
PubMed 30289444

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 11 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1 Pharmacokinetic Trial of Two Intravaginal Rings (IVRs) Containing Different Dose Strengths of Vicriviroc (MK-4176) and MK-2048
ClinicalTrials.gov ID: NCT02419456
Acronym / sponsor ID: MTN-028
Conditions: HIV Infections
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 19 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Study start: Jun 2015
Primary completion: Mar 2016 (actual)
Study completion: Mar 2016 (actual)
First posted: 17 Apr 2015 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 2

Arm	Type	Receives
MK-2048A Intravaginal Ring (IVR) (Low Dose)	Experimental	Drug: MK-2048A IVR (Low Dose)The MK-2048A IVR (Low Dose) will be inserted during the enrollment visit (Day 0), and it will be removed on Day 28.
MK-2048A IVR (Original Dose)	Experimental	Drug: MK-2048A IVR (Original Dose)The MK-2048A IVR (Original Dose) will be inserted during the enrollment visit (Day 0), and it will be removed on Day 28.

Who may qualify

Ages: 18 to 45 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (12 listed)

Born female. Note: Participants who were female at birth, who now identify as male, will not be excluded so long as they are not on female-to-male transition therapy.
Age 18 through 45 years (inclusive) at screening, verified per site SOPs (standard operating procedures)
Able and willing to provide written informed consent to be screened for and take part in this study (MTN-028)
Able and willing to provide adequate locator information, as defined by the site SOPs
HIV-uninfected, based on testing performed by study staff at screening and enrollment (per applicable algorithm in Appendix II of the protocol) and willing to receive results

Key exclusion criteria (33 listed)

Participant report of any of the following at screening or enrollment:
Reports participating in any other research study involving drugs, medical devices, or vaginal products within 60 days or less prior to enrollment
At screening or enrollment, as determined by the IoR/designee, any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease
Has any of the following laboratory abnormalities at screening:
Pregnant at either screening or enrollment. Note: A documented negative pregnancy test performed by study staff is required for inclusion; however a self-reported pregnancy is adequate for exclusion from screening/enrollment into the study.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MK-2048A IVR (Low Dose)Contains 91 mg of vicriviroc (MK-4176) and 10 mg of MK-2048.	Drug	MK-2048A Intravaginal Ring (IVR) (Low Dose)
MK-2048A IVR (Original Dose)Contains 182 mg of vicriviroc (MK-4176) and 30 mg of MK-2048.	Drug	MK-2048A IVR (Original Dose)

Primary outcome

Assessment of vaginal fluid concentrations of MK-4176 and MK-2048 during and after IVR use
Time frame: Measured through Day 35
Assessment of blood plasma concentrations of MK-4176 and MK-2048 during and after IVR use
Time frame: Measured through Day 35
Assessment of cervical tissue concentrations of MK-4176 and MK-2048 during and after IVR use
Time frame: Measured through Day 35
Number of genitourinary events Grade 1 or higher judged to be related to study product
Time frame: Measured through Day 35
As defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Dec 2004 (Clarification dated August 2009), Addendum 1, (Female Genital Grading Table for Use in Microbicide Studies)
Number of adverse events Grade 2 or higher
Time frame: Measured through Day 35
As defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Dec 2004 (Clarification dated August 2009)

1 secondary outcome

Measurement of residual drug levels in IVRs
Time frame: Measured through Day 35

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2021.
Derived from this study: PubMed 30289444Liu AY, Zhang J, Anderson PL, Wagner T, Pan Z, Peda M, Gomez K, Beamer M, Jacobson C, Strizki J, Dezzutti CS, Piper JM; MTN-028 Protocol Team for the Microbicide Trials Network. Phase 1 Pharmacokinetic Trial of 2 Intravaginal Rings Containing Different Dose Strengths of Vicriviroc (MK-4176) and MK-2048. Clin Infect Dis. 2019 Mar 19;68(7):1129-1135. doi: 10.1093/cid/ciy652.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Albert Liu, MD, MPH study chair

San Francisco Department of Public Health

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assessment of vaginal fluid concentrations of MK-4176 and MK-2048 during and after IVR use (time frame: Measured through Day 35). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02419456, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2021.