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

Phase I-B Study to Evaluate the Safety, Tolerability and Efficacy of IZN-6NVS for the Treatment of Atrophic Vaginitis or Desquamative Inflammatory Vaginitis

In this open label study, 50 eligible women will be assigned to receive the investigational product (IZN-6NVS) - 2.5 g of cream/day for 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.

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).

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:

1. Women over age 18

2. 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.

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

4. 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:

1. Subjects recruited in group 1 should not be actively treated for breast, uterine or ovarian cancer within the past year.

2. Vaginal bleeding of unknown cause within 60 days of enrollment

3. Vaginal infection requiring treatment within 30 days of enrollment

4. Any known allergy to the plant extracts in the study cream

5. Any serious disease; concomitant steroid use or sex hormone treatment

6. Endometrial thickness > 5 mm measured by ultrasound for women enrolled with diagnosis of atrophic vaginitis

7. Use of any vaginal moisturizer (e.g. Replens, Gynomonal) within 30 days of enrollment.

8. In groups 1 and 2, Use of any oral, transdermal, vaginal, or systemic estrogen or estrogen/progestin product within 30 days of enrollment.

9. Current urinary tract infection (UTI) (clinical complaints of UTI or dipstick urinalysis positive for nitrates or blood)

10. History of venous thromboembolic disease.

11. Use of another investigational agent within 12 weeks of screening.

12. 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.

13. 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.

    -