NCT04319718: FAME103

Safety and Pharmacokinetics of Two Vaginal Film Formulations Containing the Integrase Inhibitor MK-2048

Completed Phase 1 Results posted Last updated 3 March 2023

What this trial tests

Phase 1 trial testing MK-2048 High Eudragit Vaginal Film in Pharmacokinetics in 37 participants. Completed in 10 October 2022.

Timeline

19 August 2020

Primary endpoint
25 February 2022

10 October 2022

Quick facts

Lead sponsor	Hillier, Sharon, PhD
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	basic science
Enrollment	37
Start date	19 August 2020
Primary completion	25 February 2022
Estimated completion	10 October 2022
Sites	1 location across United States

Drugs / interventions tested

• MK-2048 High Eudragit Vaginal Film
• MK-2048 Low Eudragit Vaginal Film

Conditions studied

• Pharmacokinetics — all drugs for Pharmacokinetics →
• Safety — all drugs for Safety →

Sponsor

Hillier, Sharon, PhD

Who can join

Adults 18 to 45, female only, with Pharmacokinetics or Safety. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Grade 2 or Higher Adverse Events Primary · Through study completion, approximately 28 days

Number of participants who experience Grade 2 or higher adverse events

Group	Value	95% CI
High Eudragit MK-2048 Vaginal Film	2
Low Eudragit MK-2048 Vaginal Film	5

Area Under the Plasma Concentration Versus Time Curve of MK-2048 Secondary · Through study completion, approximately 28 days

Area under the plasma concentration versus time curve of MK-2048 reported as pg x day/mL. MK-2048 plasma concentration was measured at 0, 3, 5, 7, 10, 14, and 28 days after film insertion.

Group	Value	95% CI
High Eudragit MK-2048 Vaginal Film	1370	706 – 2435
Low Eudragit MK-2048 Vaginal Film	1873	563 – 3959

Area Under the Cervical Tissue Homogenate Concentration Versus Time Curve of MK-2048 Secondary · Through study completion, approximately 28 days

Area under the cervical tissue homogenate concentration versus time curve of MK-2048 reported as pg x day/mL. MK-2048 concentration was measured at 0, 3, 5, 7, 10, 14, and 28 days after film insertion.

Group	Value	95% CI
High Eudragit MK-2048 Vaginal Film	NA	NA – NA
Low Eudragit MK-2048 Vaginal Film	NA	NA – NA

Area Under the Vaginal Swab Eluent Concentration Versus Time Curve of MK-2048 Secondary · Through study completion, approximately 28 days

Area under the vaginal swab eluent concentration versus time curve of MK-2048 reported as ng x day/mL. MK-2048 concentration was measured at 0, 3, 5, 7, 10, 14, and 28 days after film insertion.

Group	Value	95% CI
High Eudragit MK-2048 Vaginal Film	543608	50535 – 3256911
Low Eudragit MK-2048 Vaginal Film	1112355	58319 – 1642201

Median Fold Change in Percent Inhibition of Human Immunodeficiency Virus-1 Replication in Cervicovaginal Lavage Fluid Secondary · Through study completion, approximately 28 days

Median fold change in in-vitro anti-human immunodeficiency virus-1 activity in cervicovaginal lavage fluid determined by the TZM-bl assay and defined as percent inhibition of human immunodeficiency virus-1 infection by luciferase for a single round of replication measured at day 28 divided by percent inhibition measured at baseline.

Group	Value	95% CI
High Eudragit MK-2048 Vaginal Film	1.01	.13 – 1.25
Low Eudragit MK-2048 Vaginal Film	.92	.09 – 1.11

Human Immunodeficiency Virus-1 p24 Core Protein Titer in Cervical Biopsies Secondary · Through study completion, approximately 28 days

Human Immunodeficiency Virus-1 infection of cervical biopsies as defined as titer of the HIV-1 p24 core protein measured by ELISA and expressed as log10 pg/mL per mg of tissue

Group	Value	95% CI
High Eudragit MK-2048 Vaginal Film	96.0	17.1 – 1210.5
Low Eudragit MK-2048 Vaginal Film	543.5	265.0 – 9050.2

Mean Change in Nugent Score Secondary · Through study completion, approximately 28 days

Mean change in the Nugent score as determined from vaginal smears. Nugent scores range from 0 to 10; 0 indicates a Lactobacillus-dominant microbiome while a score of 10 indicates a microbiome dominated by bacterial vaginosis-associated bacteria. Nugent scores were assessed at 0, 3, 5, 7, 10, 14, and 28 days after film insertion. The mean change was estimated from a mixed effects linear regression model and is defined as the average change between each post-insertion time point and the pre-insertion time point.

Group	Value	95% CI
High Eudragit MK-2048 Vaginal Film	-0.35	-0.93 – 0.24
Low Eudragit MK-2048 Vaginal Film	-0.62	-1.71 – 0.48

Adverse events — posted to ClinicalTrials.gov

Time frame: 1 month. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

High Eudragit MK-2048 Vaginal Film

Serious: 0/25 (0%)

Deaths: 0/25

Low Eudragit MK-2048 Vaginal Film

Serious: 0/12 (0%)

Deaths: 0/12

Other adverse events (10 terms — click to expand)

Reaction	System	High Eudragit MK-2048 Vagi…	Low Eudragit MK-2048 Vagin…
Abnormal vaginal discharge	Reproductive system and breast disorders	—	—
Vulvovaginal itching	Reproductive system and breast disorders	—	—
Unexpected vaginal bleeding	Reproductive system and breast disorders	—	—
Vulvovaginal irritation	Reproductive system and breast disorders	—	—
Bacterial vaginosis	Infections and infestations	—	—
Vaginal odor	Reproductive system and breast disorders	—	—
Early menses	Reproductive system and breast disorders	—	—
Vaginal dryness	Reproductive system and breast disorders	—	—
Back pain, low	Musculoskeletal and connective tissue disorders	—	—
Post-traumatic stress disorder, worsening	Psychiatric disorders	—	—

Data from ClinicalTrials.gov NCT04319718 adverse events section.

Sponsor's own description

This is a proof of concept study to determine whether an extended release vaginal film can deliver drug for seven days. Two film formulations containing MK-2048 which differ by dissolution and spreadability attributes will be compared for safety and pharmacokinetic outcomes.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Promise, perils and cautious optimism: the next frontier in long-acting modalities for the treatment and prevention of HIV.
   Philbin MM, Perez-Brumer A. · · 2022 · cited 23× · PMID 35225248 · DOI 10.1097/coh.0000000000000723