Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Advanced Clinical Research Services, LLC | OTHER |
| Phil Triolo and Associates LC | INDUSTRY |
Not provided
Not provided
Not provided
This investigation is designed to demonstrate the safety and efficacy of the VR101 lubricating intravaginal ring (IVR) in treating the symptoms of vaginal dryness. In the proposed investigation, participants will use VR101 devices and sham control rings in a crossover study design. All participants who successfully complete the crossover study will be given the option to continue using VR101 for a total of 13 consecutive weeks to evaluate the long-term safety of the new device.
CI02, A Pivotal Clinical Investigation to Evaluate the Safety and Efficacy of J3 Bioscience Lubricating Intravaginal Ring VR101 in Relieving Symptoms of Vaginal Dryness, is a multi-center, investigator- and participant-blind, randomized crossover study designed to evaluate the safety and efficacy of VR101 and establish its substantial equivalence to the predicate device, building on the results obtained in CI01, "VR101: A Pilot Study to Evaluate the Preliminary Feasibility and Safety of a Lubricating Intravaginal Ring to Relieve the Symptoms of Vaginal Dryness." The data from CI02 will be used to support a premarket 510(k) notification to the FDA to enable regulatory clearance of the device in the United States (US).
At least 60 participants (up to 69 may be enrolled to account for the anticipated drop-out rate) who consent to be enrolled and meet inclusion/exclusion criteria will be enrolled in the study. To qualify, women must be over the age of 35 who self-report having experienced vaginal dryness symptoms that interfere with daily activities, including but not limited to sexual activity, in the last 60 days; and their clinician-assigned baseline VHI score must be 22 or lower.
Enrolled participants will be randomly assigned to be treated initially by VR101 (GROUP V1S2) or a sham control (GROUP S1V2). Participants randomly assigned to GROUP V1S2 will 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, 2 additional devices will be inserted and removed serially on a 7-day schedule until a total of 4 devices are used by each study participant, with the last device removed at day 28.
Participants assigned to S1V2 will 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, 2 additional sham rings will be inserted and removed serially on a 7-day schedule until a total of 4 sham rings are used by each study participant, with the last sham ring removed at day 28.
Following completion of the first 28-day treatment course with either VR101 device or sham control, participants will undergo a 21-day "washout" period during which no products (devices or sham rings) will be used, before "crossing over" to treatment with the other product.
All participants who successfully complete the crossover study will be given the option to complete the long-term safety evaluation. V1S2 participants who elect to enter the safety study will switch back to VR101 following completion of the crossover study and use a new VR101 device every day for 13 consecutive weeks. S1V2 participants who elect to enter the safety study will continue using a new VR101 device every 7 days for 9 additional weeks, or a total of 13 consecutive weeks.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VR101 Device | Active Comparator | Subjects assigned to use randomly-assigned VR101 devices. Each device is to be used for 7 consecutive days, then replaced with a fresh device. Four each VR101 devices will be used. These will be investigated in a cross-over design that will also include consecutive use of 4 Shams, each for 7 days. |
|
| Sham Control Ring | Sham Comparator | Subjects assigned to use randomly-assigned Sham rings. Each Sham is to be used for 7 consecutive days, then replaced with a fresh sham. Four each Shams will be used. These will be investigated in a cross-over design that will also include consecutive use of 4 VR101 Devices, each for 7 days. |
|
| Long-term Safety Evaluation | Other | 13-week investigation of the safety of the use of VR101 Devices |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VR101 Device (Efficacy) | Device | Self-insertion of VR101 Device for 7 days, followed by replacement with a fresh VR101Device, until 4 each Devices have been used for 7 days each, with total consecutive device use equal to 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of VR101 Treatments at 28 Days Assessed by Change in VHI (Vaginal Health Index) Scores Assigned by Clinicians | 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). | Baseline, 28 Days |
| Serious Adverse Device Effects | Number of Participants with Serious Adverse Device Effects Over the VR101 Treatment Period | Up to 24 weeks total, comprising up to 17 weeks total VR101 use and up to 4 weeks total sham control use. |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| Vaginal Dryness Severity Survey (Population Analysis) | 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:
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. |
Inclusion Criteria:
Potential participants must:
Completely understand and sign the informed consent form (ability to read and understand the consent form in the English language).
Be female 35 years of age or older.
Express willingness to comply with the study visit schedule (see Table 4 in study procedures section).
Over the course of the study:
In the previous 60 days, have self-reported vaginal dryness that interferes with daily activities, which may include sexual intercourse
Present with a VHI score of 22 or less, as scored by a trained clinician during the initial visit
Exclusion Criteria:
Potential participants self-reporting any of the following will be ineligible for study entry:
NOTE: IUD (Intrauterine Device, e.g., ParaGard®) users may be enrolled provided they commit to exercising caution when removing VR101 as IUD strings have been noted to interfere with VR101 removal.
NOTE: Participants who have previously undergone anterior and/or posterior vaginal repair and have received a vaginal mesh implant may have difficulty placing VR101, although no safety issues with VR101 use in CI01 participants who had vaginal mesh implants were noted.
Participants must self-identify as female
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Judith Kirstein, MD, CPI | Advanced Clinical Research Services, LLC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Advanced Clinical Research, Inc. (ACR Idaho) | Meridian | Idaho | 83642 | United States | ||
| Advanced Clinical Research, Inc. (ACR Utah) |
There is no current plan to make individual patient data available to other researchers.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| FG001 | 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
| |||||||||||||
| Washout |
| |||||||||||||
| Period 2 |
| |||||||||||||
| Long-Term Safety Extension |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Efficacy of VR101 Treatments at 28 Days Assessed by Change in VHI (Vaginal Health Index) Scores Assigned by Clinicians | 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). | "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. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline, 28 Days |
|
Up to 24 weeks total, including up to 17 weeks total VR101 use and up to 4 weeks total sham use.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | VR101 | Participants for whom adverse events were reported during VR101 use. | 0 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Inability to remove ring | Product Issues | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| R. Tyler McCabe, Ph.D. | J3 Bioscience, Inc | 801-550-9956 | tmccabe@j3bio.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 7, 2017 | Sep 13, 2022 | Prot_SAP_001.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D004864 | Equipment and Supplies |
| C005703 | salicylhydroxamic acid |
Not provided
Not provided
Not provided
Participants randomly assigned to GROUP V1S2 will 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, 2 additional devices will be inserted and removed serially on a 7-day schedule until a total of 4 devices are used by each study participant, with the last device removed at day 28.
Participants assigned to S1V2 will 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, 2 additional sham rings will be inserted and removed serially on a 7-day schedule until a total of 4 sham rings are used by each study participant, with the last sham ring removed at day 28.
Following completion of the first 28-day treatment course with either VR101 or sham control, participants will undergo a 21-day "washout" period during which no devices will be used, before "crossing over" to treatment with the other device.
Not provided
Not provided
VR101 devices and Sham control rings differ only in that VR101 device rings contain glycerol-based lubricant, whereas the Sham controls do not. The product, either VR101 device or Sham ring, is randomly assigned to participants when they are enrolled in the study. Once inserted in the vagina, the devices are indistinguishable. Thus, Investigators cannot tell whether a VR101 device or Sham is in place while performing any vaginal examination. All products (VR101 devices or Sham rings) are intravaginally placed by participants in a room that is not occupied by Care Providers or Investigators, so it is impossible for them to know which product has been assigned. The packaging of all products is identical.
|
| Sham Control Ring | Other | Self-insertion of Sham Ring for 7 days, followed by replacement with a fresh Sham Ring, until 4 each Sham Rings have been used for 7 days each, with total consecutive Sham use equal to 28 days |
|
|
| VR101 Device (Safety) | Device | Following the 4-week use of shams and a 3-week washout period participants randomized to the Safety Study will use a new VR101 device every 7 days for 13 consecutive weeks. |
|
|
| 7 Days |
| Vaginal Dryness Severity Survey (Individual Analysis) | 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:
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. | 7 Days |
| VR101 Ease of Use Survey | 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:
The scores of the 67 participants are summarized below. "Favorable" scores were defined as those of 1 or higher. | First Ring Insertion |
| Number of VR101 Devices Considered as Comfortable / Uncomfortable | 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:
| Up to 4 weeks total |
| West Jordan |
| Utah |
| 84088 |
| United States |
| NOT COMPLETED |
|
| NOT COMPLETED |
|
| NOT COMPLETED |
|
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Menopausal Status | During Visit 1, each participant was asked to report her menopausal status. Specifically, a participant was defined as menopausal if she had not experienced a menstrual period in the last 12 months. | Count of Participants | Participants |
|
Combined 28-day composite VHI change scores during VR101 use across both groups / periods. |
| OG001 | Sham Control | Combined 28-day composite VHI change scores during sham control use across both groups / periods. |
|
|
| Primary | Serious Adverse Device Effects | Number of Participants with Serious Adverse Device Effects Over the VR101 Treatment Period | Posted | Count of Participants | Participants | Up to 24 weeks total, comprising up to 17 weeks total VR101 use and up to 4 weeks total sham control use. |
|
|
|
| Other Pre-specified | Vaginal Dryness Severity Survey (Population Analysis) | 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:
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. | Participants who completed their first week of VR101 use | Posted | Mean | Standard Deviation | Score on a Scale | 7 Days |
|
|
|
| Other Pre-specified | Vaginal Dryness Severity Survey (Individual Analysis) | 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:
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. | Participants who completed their first week of VR101 use | Posted | Count of Participants | Participants | 7 Days |
|
|
|
| Other Pre-specified | VR101 Ease of Use Survey | 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:
The scores of the 67 participants are summarized below. "Favorable" scores were defined as those of 1 or higher. | Posted | Count of Participants | Participants | First Ring Insertion |
|
|
|
| Other Pre-specified | Number of VR101 Devices Considered as Comfortable / Uncomfortable | 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:
| Posted | Number | Daily Diary Entries | Up to 4 weeks total |
|
|
|
| Post-Hoc | Efficacy of VR101 Treatments at 28 Days Assessed by Change in VHI (Vaginal Health Index) Scores Assigned by Clinicians - Post-Hoc Analysis 1 | 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. | Posted | Mean | Standard Error | Score on a Scale | Baseline, 28 Days |
|
|
|
| Post-Hoc | Efficacy of VR101 Treatments at 28 Days Assessed by Change in VHI (Vaginal Health Index) Scores Assigned by Clinicians - Post-Hoc Analysis 2 | 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. | Posted | Mean | Standard Error | Score on a Scale | Baseline, 28 Days |
|
|
|
| 69 |
| 0 |
| 69 |
| 46 |
| 69 |
| EG001 | Sham Control | Participants for whom adverse events were reported during Sham Control use. | 0 | 67 | 0 | 67 | 31 | 67 |
| Vaginal Discharge - Mild | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Vaginal Discomfort - Mild to Moderate | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Increased Urge / Urinary Incontinence - Mild to Moderate | Renal and urinary disorders | Non-systematic Assessment |
|
| Vaginal / Labial Bleeding / Spotting [Non-Menstrual] - Mild | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Urinary Tract Infection - Mild to Moderate | Renal and urinary disorders | Non-systematic Assessment |
|
| Vaginal Itching - Mild | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Yeast Infection - Moderate | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Abdominal Cramps / Discomfort - Moderate | General disorders | Non-systematic Assessment |
|
| Vaginal Burning Sensation - Moderate | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Vaginal Bacterial Infection - Moderate | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Urethritis - Mild | Renal and urinary disorders | Non-systematic Assessment |
|
| Malodor - Mild | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Intermittent Nausea - Moderate | General disorders | Non-systematic Assessment |
|
| Intermittent Headache - Mild | General disorders | Non-systematic Assessment |
|
| Pelvic Pain - Mild | General disorders | Non-systematic Assessment |
|
| Vaginal Irritation - Moderate | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Excessive Secretions - Mild to Moderate | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Other AEs - Not Related to Ring | General disorders | Non-systematic Assessment |
|
Not provided
Not provided