A Study of the Preliminary Efficacy of DARE-HPV to Treat High-risk Persistent Human Papillomavirus (hrHPV)

A Phase 2a, Multi-Center, Placebo-Controlled, Double-Blinded, Randomized, Dose Ranging Study of the Preliminary Efficacy of DARE-HPV to Treat Persistent High-Risk Human Papillomavirus (HPV) Genital Infection

The goal of this clinical study is to learn if DARE-HPV can treat persistent high-risk human papillomavirus (hrHPV). The primary outcome will be if the genital infection clears following treatment in 30, 60 or 90 days.

The study will look at two different doses of DARE-HPV and two different treatment durations of 14 and 21 days compared to a placebo group or 14 or 21 days of treatment.

Inclusion Criteria:

1. Provision of written informed consent prior to any study-specific procedures.

2. Premenopausal women aged 22-50 years inclusive at the time of screening visit.

3. Positive result for genital hrHPV (types 16, 18, or 'other') on at least 2 tests over the span of at least 12 months (history of persistent hrHPV infection for at least 12 months), based on review of participant's medical records. The visit 1 screening genital hrHPV test may be the second positive test.

4. Generally, in good health with no clinically significant disease as determined by the Investigator.

5. Regular menstrual cycle with an approximate 28-day cycle OR women who are amenorrheic due to effective contraception (such as levonorgestrel intrauterine system, or continuous oral contraception).

6. Agree to refrain from vaginal douching, insertion of intravaginal devices (e.g., tampons, menstrual cups), and use of condoms for at least 48 hours before the first dose of study drug through at least 72 hours after the last dose of study drug.

7. Agree to abstain from all vaginal and oral intercourse for at least 48 hours before the first dose of study drug through at least 72 hours after the last dose of study drug.

8. Women at risk of pregnancy must use a highly effective form of birth control (confirmed by the Investigator) for the entire duration of the study. Rhythm methods and consistent use of condoms will not be considered as highly effective methods of birth control. Highly effective forms of birth control include:

   • Heterosexual abstinence
   • Vasectomized male partner (provided that the male partner is the sole sexual partner of the female participant with childbearing potential and that the vasectomized partner has received medical assessment of the surgical success);
   • Oral or transdermal combined ethinyl estradiol/progestin hormonal contraception associated with inhibition of ovulation;
   • Oral, injectable or implantable progestogen-only hormone contraception associated with inhibition of ovulation (e.g., Depo-Provera™, Nexplanon, Slynd);
   • Any effective copper intrauterine device/levonorgestrel intrauterine system;
   • Female sterilization by tubal occlusion or bilateral salpingectomy;
   • Supracervical hysterectomy.

9. Ability and willingness to attend the necessary visits to the study center.

10. Ability to comprehend all study related documentation, including written informed consent form, and complete all study-related tasks including daily diary.

11. Be willing and able to adhere to the prohibitions and restrictions specified in the protocol.

Exclusion Criteria:

1. Any significant disease or disorder (e.g., cardiovascular, pulmonary, gastrointestinal, hepatic, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or may influence the results of the study, or the participant's ability to participate in the study.
2. Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during screening and at baseline, which in the opinion of the Investigator, may put the participant at risk because of her participation in the study, or may influence the results of the study, or the participant's ability to complete the entire duration of the study.
3. Cytological abnormality of the uterine cervix defined as LSIL or mild cervical intraepithelial neoplasia (CIN1), or HSIL or moderate (CIN 2) or severe (CIN 3) histology, as proven by cytology or colposcopic biopsy collected within the 12 months prior to screening or cytology at screening.
4. Pregnant, breastfeeding, or lactating women (WOCBP must have a negative urine pregnancy test at screening and at the start of treatment [i.e., Day 1]).
5. Active pelvic infection (positive for gonorrhea or chlamydial infection, positive test and symptoms for bacterial vaginosis, candida vaginitis or trichomonal vaginitis). Participants with positive results can be treated and re-tested once during screening.
6. Positive result for hepatitis B, hepatitis C antibody or human immunodeficiency virus.
7. Currently taking systemic immunosuppressants, biologics, intra-vaginal preparations, or any prescription that in the opinion of the Investigator could be a potential safety issue or interfere with the interpretation of the results.
8. Previous exposure to lopinavir/ritonavir (within 3 months prior to screening), contraindication to the use of lopinavir/ritonavir or known allergy, hypersensitivity, or intolerance to any component of lopinavir/ritonavir excipients.
9. Recent history (within 3 months prior to screening) of Stevens-Johnson syndrome, erythema multiforme, urticaria, or angioedema.
10. Receipt of any investigational product within 30 days or 5 half-lives prior to dosing.
11. Participants who, in the opinion of the Investigator, do not understand the information and procedures of the study, or would not be compliant with them (in particular, the study restrictions and risks involved).