Trial Outcomes & Findings for Use of J3 Bioscience Lubricating Intravaginal Ring VR101 to Relieve the Symptoms of Vaginal Dryness (NCT NCT03150407)

NCT ID: NCT03150407

Last Updated: 2022-11-07

Results Overview

Recruitment status

COMPLETED

Study phase

Target enrollment

72 participants

Primary outcome timeframe

Baseline, 28 Days

Results posted on

2022-11-07

Participant Flow

Participant milestones

Participant milestones
Measure	V1S2 Participants randomly assigned to GROUP V1S2 were instructed to insert a VR101 device and leave it in place for 7 days, then remove the first device and replace it with a fresh device on day 7. Subsequently, participants were instructed to insert and remove 2 additional devices serially on a 7-day schedule until a total of 4 devices were used by each participant, with the last device removed at day 28. Following completion of the first 28-day treatment course with VR101, participants abstained from device use during a 21-day "washout" period before "crossing over" to use of the sham control for 4 weeks in an identical manner to that of VR101 use in the initial period. All participants who successfully completed both treatment periods were given the option to complete the long-term safety evaluation (13 additional weeks of VR101 use).	S1V2 Participants assigned to S1V2 were instructed to insert a sham control ring and leave it in place for 7 days, then remove the first ring and replace it with a new ring on day 7. Subsequently, they were instructed to insert and remove 2 additional sham rings serially on a 7-day schedule until a total of 4 sham rings were used by each participant, with the last sham ring removed at day 28. Following completion of the first 28-day treatment course with the sham control, participants abstained from device use during a 21-day "washout" period before "crossing over" to use of VR101 for 4 weeks in an identical manner to that of sham control use in the initial period. All participants who successfully completed both treatment periods were given the option to complete the long-term safety evaluation (9 additional weeks of VR101 use, for a total of 13 consecutive weeks of VR101).
Period 1 STARTED	36	36
Period 1 COMPLETED	32	34
Period 1 NOT COMPLETED	4	2
Washout STARTED	32	34
Washout COMPLETED	31	33
Washout NOT COMPLETED	1	1
Period 2 STARTED	31	33
Period 2 COMPLETED	30	33
Period 2 NOT COMPLETED	1	0
Long-Term Safety Extension STARTED	27	30
Long-Term Safety Extension COMPLETED	26	27
Long-Term Safety Extension NOT COMPLETED	1	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Use of J3 Bioscience Lubricating Intravaginal Ring VR101 to Relieve the Symptoms of Vaginal Dryness

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	V1S2 n=36 Participants Participants randomly assigned to GROUP V1S2 were instructed to insert a VR101 device and leave it in place for 7 days, then remove the first device and replace it with a fresh device on day 7. Subsequently, participants were instructed to insert and remove 2 additional devices serially on a 7-day schedule until a total of 4 devices were used by each participant, with the last device removed at day 28.	S1V2 n=36 Participants Participants assigned to S1V2 were instructed to insert a sham control ring and leave it in place for 7 days, then remove the first ring and replace it with a new ring on day 7. Subsequently, they were instructed to insert and remove 2 additional sham rings serially on a 7-day schedule until a total of 4 sham rings were used by each participant, with the last sham ring removed at day 28.	Total n=72 Participants Total of all reporting groups
Age, Continuous	59.1 years STANDARD_DEVIATION 8.5 • n=5 Participants	59.4 years STANDARD_DEVIATION 8.5 • n=7 Participants	59.2 years STANDARD_DEVIATION 8.5 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	36 Participants n=7 Participants	72 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants	34 Participants n=7 Participants	65 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	35 Participants n=5 Participants	35 Participants n=7 Participants	70 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Menopausal Status Menopausal	36 Participants n=5 Participants	35 Participants n=7 Participants	71 Participants n=5 Participants
Menopausal Status Not Menopausal	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 28 Days

Population: "Completers Only": Participants that completed both study periods. "Worst-Case, Non-Statistical, Per-Protocol": Subjects who didn't complete a study period were assigned the last available score for Day 28. Subjects who missed an entire study period were assigned the worst-performing change score from the remaining population for Day 28. LOCF: Same as the per-protocol group, except participants missing an entire study period were assigned a change score of 0 (no efficacy) for that period.

Outcome measures

Outcome measures
Measure	VR101 n=72 Participants Combined 28-day composite VHI change scores during VR101 use across both groups / periods.	Sham Control n=72 Participants Combined 28-day composite VHI change scores during sham control use across both groups / periods.	Worsened Participants whose vaginal dryness severity worsened (higher score)
Efficacy of VR101 Treatments at 28 Days Assessed by Change in VHI (Vaginal Health Index) Scores Assigned by Clinicians Completers Only	1.76 Score on a Scale Standard Deviation 3.32	0.55 Score on a Scale Standard Deviation 3.70	—
Efficacy of VR101 Treatments at 28 Days Assessed by Change in VHI (Vaginal Health Index) Scores Assigned by Clinicians Worst-Case, Non-Statistical, Per-Protocol	1.38 Score on a Scale Standard Deviation 3.55	0.97 Score on a Scale Standard Deviation 4.04	—
Efficacy of VR101 Treatments at 28 Days Assessed by Change in VHI (Vaginal Health Index) Scores Assigned by Clinicians LOCF	1.63 Score on a Scale Standard Deviation 3.21	0.49 Score on a Scale Standard Deviation 3.56	—

PRIMARY outcome

Timeframe: Up to 24 weeks total, comprising up to 17 weeks total VR101 use and up to 4 weeks total sham control use.

Number of Participants with Serious Adverse Device Effects Over the VR101 Treatment Period

Outcome measures

Outcome measures
Measure	VR101 n=72 Participants Combined 28-day composite VHI change scores during VR101 use across both groups / periods.	Sham Control n=72 Participants Combined 28-day composite VHI change scores during sham control use across both groups / periods.	Worsened Participants whose vaginal dryness severity worsened (higher score)
Serious Adverse Device Effects	0 Participants	0 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 7 Days

Population: Participants who completed their first week of VR101 use

Claim 1: VR101 relieves the symptoms of vaginal dryness for up to 7 days. Participants were asked to rate the severity of their vaginal dryness on a four-point scale throughout the investigation. Responses were assigned numerical values as follows: * "I have not experienced vaginal dryness" (assigned a score of 0) * "Mild" (assigned a score of 1) * "Moderate" (assigned a score of 2) * "Severe" (assigned a score of 3) To assess the ability of VR101 to relieve the symptoms of dryness on the final day of ring use (nominally 7 days), participants were asked to report their dryness severity in the last 24 hours when removing their first VR101. This score was compared to the participant's assessment of their dryness severity in the week prior to VR101 use.

Outcome measures

Outcome measures
Measure	VR101 n=66 Participants Combined 28-day composite VHI change scores during VR101 use across both groups / periods.	Sham Control n=66 Participants Combined 28-day composite VHI change scores during sham control use across both groups / periods.	Worsened Participants whose vaginal dryness severity worsened (higher score)
Vaginal Dryness Severity Survey (Population Analysis)	0.71 Score on a Scale Standard Deviation 0.82	1.77 Score on a Scale Standard Deviation 0.76	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 7 Days

Population: Participants who completed their first week of VR101 use

Outcome measures

Outcome measures
Measure	VR101 n=66 Participants Combined 28-day composite VHI change scores during VR101 use across both groups / periods.	Sham Control n=66 Participants Combined 28-day composite VHI change scores during sham control use across both groups / periods.	Worsened n=66 Participants Participants whose vaginal dryness severity worsened (higher score)
Vaginal Dryness Severity Survey (Individual Analysis)	48 Participants	15 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: First Ring Insertion

Claim 2: VR101 is easy to use by following the provided instructions. To assess the ability to use VR101 by following the instructions for use and without professional medical assistance, participants were asked to rate their level of agreement with the following statement, the ring was easy to use by following the provided instructions, when removing their first VR101. The following scale was used to rate the level of agreement: * "Disagree completely" (assigned a score of -4) * "Disagree a lot" (assigned a score of -3) * "Disagree somewhat" (assigned a score of -2) * "Disagree a little" (assigned a score of -1) * "Neither agree nor disagree" (assigned a score of 0) * "Agree a little" (assigned a score of 1) * "Agree somewhat" (assigned a score of 2) * "Agree a lot" (assigned a score of 3) * "Agree completely" (assigned a score of 4) The scores of the 67 participants are summarized below. "Favorable" scores were defined as those of 1 or higher.

Outcome measures

Outcome measures
Measure	VR101 n=67 Participants Combined 28-day composite VHI change scores during VR101 use across both groups / periods.	Sham Control n=67 Participants Combined 28-day composite VHI change scores during sham control use across both groups / periods.	Worsened Participants whose vaginal dryness severity worsened (higher score)
VR101 Ease of Use Survey	62 Participants	5 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 4 weeks total

Claim 3: VR101 is comfortable during use In each daily diary, the participant was asked to rate her level of agreement with the statement "the ring was comfortable to me today." The following scale was used to rate the level of agreement: * "Disagree completely" (assigned a score of -4) * "Disagree a lot" (assigned a score of -3) * "Disagree somewhat" (assigned a score of -2) * "Disagree a little" (assigned a score of -1) * "Neither agree nor disagree" (assigned a score of 0) * "Agree a little" (assigned a score of 1) * "Agree somewhat" (assigned a score of 2) * "Agree a lot" (assigned a score of 3) * "Agree completely" (assigned a score of 4)

Outcome measures

Outcome measures
Measure	VR101 n=72 Participants Combined 28-day composite VHI change scores during VR101 use across both groups / periods.	Sham Control n=72 Participants Combined 28-day composite VHI change scores during sham control use across both groups / periods.	Worsened Participants whose vaginal dryness severity worsened (higher score)
Number of VR101 Devices Considered as Comfortable / Uncomfortable	1629 Daily Diary Entries	215 Daily Diary Entries	—

POST_HOC outcome

Timeframe: Baseline, 28 Days

The Vaginal Health Index (VHI) ranges from 5 to 20 and is calculated via addition of clinician-determined ratings for Vaginal Elasticity, Fluid Volume, Epithelial Integrity, Moisture and pH (each ranges from 1 to 5, with 5 being the best). The SAS Proc Mixed model was employed with Kenward-Roger degrees of freedom. The treatment effect was defined as the change in VHI between baseline and day 28. The subject, sequence, period and treatment were all included as effects. Furthermore, last observation carried forward (LOCF) for the raw score was used for cases where the Day 28 observation was missing within a treatment period if the subject had at least one measurement, including baseline, within the treatment period.

Outcome measures

Outcome measures
Measure	VR101 n=72 Participants Combined 28-day composite VHI change scores during VR101 use across both groups / periods.	Sham Control n=72 Participants Combined 28-day composite VHI change scores during sham control use across both groups / periods.	Worsened Participants whose vaginal dryness severity worsened (higher score)
Efficacy of VR101 Treatments at 28 Days Assessed by Change in VHI (Vaginal Health Index) Scores Assigned by Clinicians - Post-Hoc Analysis 1 Baseline Included as Covariate	1.59 Score on a Scale Standard Error 0.33	0.44 Score on a Scale Standard Error 0.34	—
Efficacy of VR101 Treatments at 28 Days Assessed by Change in VHI (Vaginal Health Index) Scores Assigned by Clinicians - Post-Hoc Analysis 1 Baseline not included as Covariate	1.68 Score on a Scale Standard Error 0.41	0.35 Score on a Scale Standard Error 0.41	—

POST_HOC outcome

Timeframe: Baseline, 28 Days

The Vaginal Health Index (VHI) ranges from 5 to 20 and is calculated via addition of clinician-determined ratings for Vaginal Elasticity, Fluid Volume, Epithelial Integrity, Moisture and pH (each ranges from 1 to 5, with 5 being the best). The "missingness" of VHI scores was evaluated in detail, with the eventual conclusion that a missing at random (MAR) assumption was plausible for the missing VHI scores (at either day 0 or day 28). This conclusion was supported by the observation that no participants reported withdrawing due to a lack of perceived VR101 efficacy. The analysis also modeled raw VHI values rather than the treatment effect (change in VHI from day 0 to day 28), but reported summary statistics in terms of net treatment effect. No LOCF imputations were performed.

Outcome measures

Outcome measures
Measure	VR101 n=72 Participants Combined 28-day composite VHI change scores during VR101 use across both groups / periods.	Sham Control Combined 28-day composite VHI change scores during sham control use across both groups / periods.	Worsened Participants whose vaginal dryness severity worsened (higher score)
Efficacy of VR101 Treatments at 28 Days Assessed by Change in VHI (Vaginal Health Index) Scores Assigned by Clinicians - Post-Hoc Analysis 2 Classical Mixed Model	0.48 Score on a Scale Standard Error 0.21	—	—
Efficacy of VR101 Treatments at 28 Days Assessed by Change in VHI (Vaginal Health Index) Scores Assigned by Clinicians - Post-Hoc Analysis 2 Unequal Variance Model	0.49 Score on a Scale Standard Error 0.20	—	—

Adverse Events

VR101

Serious events: 0 serious events

Other events: 46 other events

Deaths: 0 deaths

Sham Control

Serious events: 0 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

R. Tyler McCabe, Ph.D.

J3 Bioscience, Inc

Phone: 801-550-9956

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	VR101 n=69 participants at risk Participants for whom adverse events were reported during VR101 use.	Sham Control n=67 participants at risk Participants for whom adverse events were reported during Sham Control use.
Product Issues Inability to remove ring	8.7% 6/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	6.0% 4/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
Reproductive system and breast disorders Vaginal Discharge - Mild	2.9% 2/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	3.0% 2/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
Reproductive system and breast disorders Vaginal Discomfort - Mild to Moderate	10.1% 7/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	4.5% 3/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
Renal and urinary disorders Increased Urge / Urinary Incontinence - Mild to Moderate	7.2% 5/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	3.0% 2/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
Reproductive system and breast disorders Vaginal / Labial Bleeding / Spotting [Non-Menstrual] - Mild	5.8% 4/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	3.0% 2/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
Renal and urinary disorders Urinary Tract Infection - Mild to Moderate	4.3% 3/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	1.5% 1/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
Reproductive system and breast disorders Vaginal Itching - Mild	2.9% 2/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	1.5% 1/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
Reproductive system and breast disorders Yeast Infection - Moderate	2.9% 2/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	0.00% 0/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
General disorders Abdominal Cramps / Discomfort - Moderate	1.4% 1/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	3.0% 2/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
Reproductive system and breast disorders Vaginal Burning Sensation - Moderate	1.4% 1/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	1.5% 1/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
Reproductive system and breast disorders Vaginal Bacterial Infection - Moderate	1.4% 1/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	0.00% 0/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
Renal and urinary disorders Urethritis - Mild	1.4% 1/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	0.00% 0/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
Reproductive system and breast disorders Malodor - Mild	1.4% 1/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	0.00% 0/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
General disorders Intermittent Nausea - Moderate	1.4% 1/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	0.00% 0/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
General disorders Intermittent Headache - Mild	1.4% 1/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	0.00% 0/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
General disorders Pelvic Pain - Mild	0.00% 0/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	1.5% 1/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
Reproductive system and breast disorders Vaginal Irritation - Moderate	0.00% 0/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	1.5% 1/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
Reproductive system and breast disorders Excessive Secretions - Mild to Moderate	4.3% 3/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	0.00% 0/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
General disorders Other AEs - Not Related to Ring	50.7% 35/69 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.	29.9% 20/67 • Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.