A Phase 2 Trial to Evaluate the Safety and Efficacy of UB-621

Study Overview
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Brief Summary
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To evaluate the efficacy of two dose levels of UB-621 administration in reducing the HSV-2 genital shedding rate in patients with recurrent genital HSV-2 infection.

Detailed Description
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This is a 2-stage, randomized, double-blind, dose-ranging, multi-center phase 2 study designed to evaluate the efficacy, safety, and PK of UB-621 given at 2.5 or 5 mg/kg in adult subjects with recurrent genital HSV-2 infection. The study consists of 2 stages of enrollments, in which 40 subjects will be enrolled in the first stage and randomly assigned to receive placebo or UB-621 at 2.5 mg/kg in a 1:3 ratio into Cohort 1 at Bv6 (Day B57), and another 40 subjects will be enrolled in the second stage and randomly assigned to receive placebo or UB-621 at 5 mg/kg in a 1:3 ratio into Cohort 2 at Bv6 (Day B57) after review by the Data Safety Monitoring Committee (DSMC). The DSMC will review safety data after all subjects of Cohort 1 complete the visit Fv6 (Day F28) and make the recommendation whether to proceed with enrollment for Cohort 2.

Official Title
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A Two-Stage, Randomized, Double-Blind, Dose-Ranging, Phase 2 Trial to Evaluate the Safety and Efficacy of UB-621 on HSV Shedding in Adults With Recurrent Genital HSV-2 Infection.

Conditions
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Genital Herpes

Intervention / Treatment
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* Biological: UB-621
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be at least 18 years of age inclusive. Subject must be HSV-2 seropositive Subjects have a history of recurrent genital herpes in the past year Subjects have a negative result on the HIV Ab/Ag assay Subjects must agree to use contraception during study participation Subjects must be willing NOT to use any topical genital therapy and systemic anti-HSV therapy from the beginning of the study till the end of week 16. Subjects must be willing to collect a swab each day from their genital area (non-lesional as well as lesional, if appropriate) during the swabbing periods, which are 8 weeks prior to and upon the administration of study drug. Female subjects must have a negative serum β-HCG at Screening and a negative urine pregnancy test prior to study drug administration. Exclusion Criteria: Serious medical conditions, including poorly controlled diabetes, significant autoimmune diseases, co-existing sexually transmitted disease presentation (except HSV) in the anogenital area, etc. that may interfere with the assessment of the efficacy of UB-621. Documented HSV resistance to acyclovir, valacyclovir, famciclovir, or penciclovir History or current evidence of malignancy except for a localized non-melanoma skin cancer Known immunosuppression Exposure to HSV vaccine Medical history of macular or maculopapular skin reactions to antibody (ie, as evidenced by IgG or plasma administration) Any other conditions that in the judgment of the Investigator would preclude successful completion of the clinical study Treatment with systemic steroids or other immunomodulating agents within 30 days prior to Screening or planned treatment with systemic steroids or immunomodulators during the study period. Renal impairment and/or hepatic impairment ECG abnormalities of clinical relevance or cardiovascular conditions

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Placebo (volume equivalent to 2.5 mg/kg UB-621) 2.5 mg/kg UB-621 | Biological: UB-621<br>* Monoclonal antibody by SC injection<br>Other: Placebo<br>* The placebo is a sterile, clear and colorless or slightly yellow liquid, contains the same composition as UB-621 except drug substance. It is given by SC injection.<br>|
| Experimental: Cohort 2<br>Placebo (volume equivalent to 5 mg/kg UB-621) 5 mg/kg UB-621 | Biological: UB-621<br>* Monoclonal antibody by SC injection<br>Other: Placebo<br>* The placebo is a sterile, clear and colorless or slightly yellow liquid, contains the same composition as UB-621 except drug substance. It is given by SC injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of HSV-2 shedding rate. | The primary endpoint for this study is to evaluate the reduction in HSV-2 shedding rate within subjects in the Baseline Period versus Follow-up Period. | 112 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of HSV-2 viral load | Anogenital swab samples collected from subjects during the Baseline Period and Follow-up Period will be used to quantify HSV-2 DNA copies to evaluate efficacy of UB-621 in reducing viral load. | 112 days | 
| change of genital lesion rates | Subject self-assessment of genital lesions will be recorded in subject diary as daily routine tasks from Bv1 (Day B1) until Fv11/EOS visit (Day F140). Data from subject self-assessment of genital lesions will be used to evaluate the efficacy of UB-621 in reducing genital lesions rates. Genital lesion rate will be measured by the number of days with lesion(s) reported divided by the number of days of study periods (Baseline Period, Transition Period, or Follow-up Period). Reduction in genital lesion rates will be evaluated before and after study drug treatment within subjects (Baseline versus Follow-up values). | 140 days | 
| Clinical and Subclinical HSV-2 Shedding Rates | Daily record of subject self-assessment of genital lesions in subject diary in addition to anogenital swabs collected daily from subjects during the Baseline and Follow-up Periods will be used to evaluate the efficacy of UB-621 in reducing clinical (lesional) and subclinical (non-lesional) HSV-2 shedding rates. | 196 days | 
| Rate of HSV-2 Shedding Episodes | Another secondary efficacy assessment includes the rate of HSV-2 shedding episodes as measured by the number of onsets of shedding episodes divided by the total number of days with swabs collected. Shedding episodes are defined as consecutive HSV-2 positive swab results including no more than 1 consecutive negative result or missed swab. The episodes are preceded and followed by 2 consecutive negative swab results. Daily record of subject self-assessment of genital lesions in subject diary in addition to anogenital swabs collected daily from subjects during the Baseline and Follow-up Periods will be used to evaluate the efficacy of UB-621 in reducing the rate of HSV-2 shedding episodes. Reduction in the rate of HSV-2 shedding episodes will be evaluated before and after study drug treatment within subjects (Baseline versus Follow-up values). | 196 |