Genital Herpes
Conditions
Keywords
AIC316, Viral shedding
Brief summary
The aim of the study is to evaluate the safety and efficacy of AIC316 (pritelivir) 100 mg once daily compared to valacyclovir 500 mg once daily for the prevention of HSV-2 genital shedding.
Detailed description
Enrolled patients with Mucocutaneous genital HSV, will be randomized to receive either AIC326 or Valacyclovir first and then will be crossed over to receive the opposite Intervention. The study will consist of two treatment periods of 28 days separated by a washout period of 28 days.
Interventions
DRUGAIC316
100 mg oral administration
DRUGValacyclovir
500 mg oral administration
Sponsors
Medpace, Inc.
AiCuris Anti-infective Cures AG
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult, immunocompetent men and women in good health of any ethnic group * Seropositive for Herpes Simplex Virus Type 2 (HSV-2) * History of recurrent episodes (\>=4 to \<=9) of genital herpes for at least 12 months and willingness to obtain 4 swabs per day.
Exclusion criteria
* Present episode of genital herpes at time of randomization * Clinically relevant acute or chronic infections (excluding HSV-2) * Known intolerance to valacyclovir, acyclovir, or any component of the formulation * Documented HSV resistance to acyclovir, valacyclovir, famciclovir or penciclovir
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Within-subject Genital HSV Mucocutaneous Shedding Rate | 28 days | Subjects were assessed for within-subject genital HSV mucocutaneous shedding rate, as calculated by the number of HSV-positive swabs per subject relative to the total number of swabs collected per subject. The swab test detects the presence of herpes virus DNA. A swab was regarded as positive for HSV-DNA if at least 3 HSV genome copies were detected by quantitative PCR per reaction (equaling 150 copies per mL of swab collection medium). When multiple swabs were available from the same time point (e.g., genital and lesional swab), the swab with the highest copy number was retained for computation of the shedding rate. |
| Overall Shedding Rate | 28 days | Subjects were assessed for overall shedding rate as the total number of HSV-positive swabs per treatment group divided by the number of swabs collected per treatment group. |
Countries
United States
Participant flow
Pre-assignment details
150 subjects were screened, 59 were screen failures (did not meet study eligibility requirements: 35, withdrawal of Consent 1, Lost to Follow-up 1, Other 22). 91 subjects were randomized.
Participants by arm
| Arm | Count |
|---|---|
| AIC316, Then Valacyclovir Participants first received AIC316 100 mg once daily for 28 days. After a washout period of 28 days, they then received Valacyclovir 500 mg once daily for 28 days. | 45 |
| Valacyclovir, Then AIC316 Participants first received Valacyclovir 500 mg once daily for 28 days. After a washout period of 28 days, they then received AIC316 100 mg once daily for 28 days. | 46 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1: First Intervention (28 Days) | Adverse Event | 1 | 2 |
| Period 1: First Intervention (28 Days) | Patient was non-compliant with study medication, swabbing and maintaining diary | 0 | 1 |
| Period 1: First Intervention (28 Days) | Protocol Violation | 0 | 1 |
| Period 1: First Intervention (28 Days) | Termination of the Study by the Investigator or Sponsor | 5 | 6 |
| Period 1: First Intervention (28 Days) | Withdrawal by Subject | 1 | 0 |
| Period 2: Second Intervention (28 Days) | Termination of the Study by the Investigator or Sponsor | 3 | 4 |
| Period 2: Second Intervention (28 Days) | Withdrawal by Subject | 0 | 1 |
| Washout Period: 28 Days | Termination of the Study by the Investigator or Sponsor | 5 | 3 |
| Washout Period: 28 Days | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Valacyclovir, Then AIC316 | Total | AIC316, Then Valacyclovir |
|---|---|---|---|
| Age, Continuous | 45.5 Years STANDARD_DEVIATION 11.4 | 45.4 Years STANDARD_DEVIATION 12.26 | 45.2 Years STANDARD_DEVIATION 13.22 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 14 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 77 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 16 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 66 Participants | 37 Participants |
| Sex: Female, Male Female | 29 Participants | 57 Participants | 28 Participants |
| Sex: Female, Male Male | 17 Participants | 34 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 78 |
| other Total, other adverse events | 48 / 77 | 54 / 78 |
| serious Total, serious adverse events | 0 / 77 | 0 / 78 |
Outcome results
Primary
Overall Shedding Rate
Subjects were assessed for overall shedding rate as the total number of HSV-positive swabs per treatment group divided by the number of swabs collected per treatment group.
Time frame: 28 days
Population: Full Analysis Set - defined as all randomized subjects who took trial medication at least once and provided at least 1 analyzable genital-perianal swab (not including the training swab) during the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AIC316 | Overall Shedding Rate | 2.4 percentage of positive swabs |
| Valacyclovir | Overall Shedding Rate | 5.2 percentage of positive swabs |
Primary
Within-subject Genital HSV Mucocutaneous Shedding Rate
Subjects were assessed for within-subject genital HSV mucocutaneous shedding rate, as calculated by the number of HSV-positive swabs per subject relative to the total number of swabs collected per subject. The swab test detects the presence of herpes virus DNA. A swab was regarded as positive for HSV-DNA if at least 3 HSV genome copies were detected by quantitative PCR per reaction (equaling 150 copies per mL of swab collection medium). When multiple swabs were available from the same time point (e.g., genital and lesional swab), the swab with the highest copy number was retained for computation of the shedding rate.
Time frame: 28 days
Population: All subjects who received at least one dose of trial medication and provided at least 1 analyzable genital-perianal swab (not including the training swab) during the treatment period were included in the efficacy analysis (Full Analysis Set).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AIC316 | Within-subject Genital HSV Mucocutaneous Shedding Rate | 2.3 percentage of positive swaps per subject | Standard Deviation 5.2 |
| Valacyclovir | Within-subject Genital HSV Mucocutaneous Shedding Rate | 4.9 percentage of positive swaps per subject | Standard Deviation 10.8 |
p-value: <0.000195% CI: [0.3, 0.63]non-linear mixed effects model