Maintenance Dose Study of GEN-003 in Subjects With Genital Herpes Infection

This study is a randomized, double-blind, placebo-controlled clinical trial of GEN-003 in subjects who have received previous doses of GEN-003 in the GEN-003-003 clinical trial. Eligible subjects will be randomized in a 1:1 ratio to receive 1 intramuscular (IM) dose (the maintenance dose) of GEN-003 or placebo.

Subjects will use a daily electronic reporting tool for reporting the presence or absence of genital herpes lesions, and severity of genital herpes symptoms.

GEN-003-005 was originally designed to follow subjects for 12 months after the maintenance dose but a business decision, unrelated to product safety, was made by Genocea Biosciences in 3Q2017 to cease GEN-003 spending and activities.

• GEN-003 (Biological), also known as HSV Therapeutic Vaccine: HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens: internal fragment of the immediate early (IE) protein ICP4 and glycoprotein D
• Matrix-M2 (Biological), also known as Adjuvant: Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.
• 0.9% normal saline (Other): Placebo

Primary outcomes

• Percentage of Days With Genital Herpes Lesions [The 6-month period after vaccination]: Subject-reported via electronic diary

Secondary outcomes

• Number of Genital Herpes Recurrences [The 6-month period after vaccination]: Subject-reported via electronic diary
• Number of Subjects Without Genital Herpes Recurrence [6 months after vaccination]: Subject-reported via electronic diary
• Days Until First Genital Herpes Recurrence [The 6-month period after vaccination]: Subject-reported via electronic diary
• Duration of Genital Herpes Recurrences [The 6-month period after vaccination]: Time in days per genital herpes recurrence

Sex: All

Inclusion Criteria:

* Completed Study GEN-003-003
* Received all 3 GEN-003 doses (any dose combination) in Study GEN-003-003
* Received last dose of GEN-003 within 11 to 18 months prior
* Reported data in the daily electronic reporting period on at least 80% of days in Study GEN-003-003
* Collected at least 45 swabs (of 56 total expected swabs) during the Month 11 to 12 swab collection period in Study GEN-003-003
* Willing and able to provide written informed consent
* Willing to perform and comply with all study procedures
* Postmenopausal or willing to practice a highly effective method of contraception for 28 days before and 90 days after enrollment

Exclusion Criteria:

* Did not meet all eligibility criteria in Study GEN-003-003, or received incorrect treatment in Study GEN-003-003
* Use of suppressive antiviral medication within 14 days prior
* Use of topical steroids or antiviral medication in the anogenital region within 14 days prior
* Use of tenofovir, lysine, or other medication or supplement known or purported to affect HSV recurrence frequency or intensity within 14 days prior
* History of any form of ocular HSV infection, HSV-related erythema multiforme, or herpes meningitis or encephalitis
* Immunocompromised individuals
* Diagnosis or suspicion of an AESI
* Diagnosis or suspicion of any other autoimmune disease not listed in Appendix 4 of the protocol
* Vaccine-related SAE in GEN-003-003
* Known current infection with HIV or hepatitis B or C virus
* History of hypersensitivity to any component of the vaccine
* Prior receipt of another vaccine containing HSV-2 antigens other than GEN-003
* Receipt of any IP within 30 days prior to the maintenance dose of GEN-003/placebo
* Receipt of any blood product within 90 days prior to the maintenance dose
* Receipt of a live vaccine within 28 days prior to or any other vaccine within 14 days prior to maintenance dose
* Planned use of any vaccine from the maintenance dose to 28 days after the maintenance dose
* Pregnant or nursing women
* History of drug or alcohol abuse
* Other active, uncontrolled comorbidities
* Changes to medication used to manage an underlying comorbidity within 60 days prior

Participant flow

Outcome results

• Percentage of Days With Genital Herpes Lesions (Primary), Median, percentage of days: GEN-003 2.58 (0.0 to 21.8); Placebo 4.23 (0.0 to 13.5) (p 0.7474)
• Number of Genital Herpes Recurrences (Secondary), Median, recurrences: GEN-003 1.50 (0.0 to 6.0); Placebo 1.50 (0.0 to 9.0) (p 0.6450)
• Number of Subjects Without Genital Herpes Recurrence (Secondary), Count of participants, Participants: GEN-003 1; Placebo 3 (p 0.3157)
• Days Until First Genital Herpes Recurrence (Secondary), Median, days: GEN-003 25 (6.0 to 85.0); Placebo 51 (17.0 to 116.0) (p 0.3869)
• Duration of Genital Herpes Recurrences (Secondary), Median, days: GEN-003 2.83 (1 to 7); Placebo 3.40 (1 to 6) (p 0.2200)

Adverse events

Time frame: Local reactions and systemic events were systematically collected for 7 days after the maintenance dose. AEs were recorded for 12 months of followup after the maintenance dose administration.

Other adverse events by term

Limitations and caveats: Small numbers of enrolled subjects likely led to a lack of statistical power. After a 2017 business decision to cease GEN-003 spending, the outcome measures were reduced to 6 months of follow up, rather than the originally planned 12 months.

• Study Protocol (PDF, 2017-10-13)
• Statistical Analysis Plan (PDF, 2018-02-07)