Phase I-B Study to Evaluate the Safety, Tolerability and Efficacy of IZN-6NVS for the Treatment of AV and DIV

This will be a Phase IB study comprised of three study groups:

• Group 1: Women who are naturally or surgically menopausal and symptomatic for AV, but who decline treatment with topical or systemic estrogen.
• Group 2: Women rendered menopausal as a result of pharmacologic treatment (including, but not limited to, aromatase inhibitor treatment, selective estrogen receptor modifiers (SERMs), and GnRH analog treatment), who decline treatment with topical or systemic estrogen.
• Group 3: Pre-menopausal women diagnosed with DIV.

The study will evaluate safety, tolerability and efficacy of IZN-6NVS vaginal cream, in the treatment of atrophic vaginitis (AV) and desquamative inflammatory vaginitis (DIV).

20 eligible women of groups 1 and 2 and up to 10 eligible women of group 3 will be assigned to receive 2.5 g of cream/day for the first 14 days, followed by 3 applications per week for the next 4 weeks. Clinical assessment of the severity of vaginitis will be performed at baseline and after 2 and 6 weeks of treatment, which will be the end of the study. Patient reported symptom severity will be assessed by questionnaire at baseline and after 2 and 6 weeks of treatment, and at follow-up.

Inclusion criteria

• Women over age 18
• For groups 1 and 2:

I. Self-reported amenorrhea for at least 12 months or documentation of menopause based on serum E2 ≤ 150 pg/ml.

II. Self-reporting of at least one moderate to severe symptom of vaginal atrophy on a 4-point scale (0=none; 1=mild; 2=moderate; 3=severe):

• Vaginal dryness
• Vaginal discomfort or irritation
• Vaginal itching
• Vaginal pain associated with sexual activity
• Vaginal discharge
• Vaginal Malodor III. Clinical impression of atrophy based on examination of vaginal cytological smear.

IV. Vaginal pH >4.5

V. Endometrial thickness ≤5 mm as determined by US, with no abnormalities noted.

• For group 3 (DIV): Clinical diagnosis of DIV in pre-menopausal women without estrogen deficiency.
• For all groups:

I. Willing to comply with use of an intravaginal cream containing S. nigra, C. asiatica, and E. purpurea extracts.

II. Normal PAP smear within the last 3 years. III. Able to provide informed consent. -

Exclusion criteria

• Subjects recruited in group 1 should not be actively treated for breast, uterine or ovarian cancer within the past year.
• Vaginal bleeding of unknown cause within 60 days of enrollment
• Vaginal infection requiring treatment within 30 days of enrollment
• Any known allergy to the plant extracts in the study cream
• Any serious disease; concomitant steroid use or sex hormone treatment
• Endometrial thickness > 5 mm measured by ultrasound for women enrolled with diagnosis of atrophic vaginitis
• Use of any vaginal moisturizer (e.g. Replens, Gynomonal) within 30 days of enrollment.
• In groups 1 and 2, Use of any oral, transdermal, vaginal, or systemic estrogen or estrogen/progestin product within 30 days of enrollment.
• Current urinary tract infection (UTI) (clinical complaints of UTI or dipstick urinalysis positive for nitrates or blood)
• History of venous thromboembolic disease.
• Use of another investigational agent within 12 weeks of screening.
• Any medical or psychiatric condition that, in the investigator's opinion, would preclude the subject from complying with the study protocol, including the completion of questionnaires.
• Subjects with DIV who are pregnant or trying to become pregnant will not be included in the study. Similarly, if a subject with DIV becomes pregnant during the study, that patient will be removed from the study.

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