Herpes Simplex
Conditions
Brief summary
To evaluate the efficacy and safety of ASP2151 in patients with herpes simplex.
Detailed description
A double-blind, randomized, placebo-controlled, parallel-group study will be conducted to evaluate the efficacy and safety of ASP2151 in patients with herpes simplex (labial/facial herpes or recurrent genital herpes). The efficacy will be evaluated for the primary endpoint defined as, the proportion of subjects achieving lesion healing by Day 8 of study treatment to demonstrate the superiority of ASP2151 to placebo. The safety will be evaluated based on adverse events, laboratory tests, vital signs, and ECGs.
Interventions
DRUGASP2151
200 mg once daily
DRUGASP2151 placebo
once daily
Sponsors
Maruho Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with a rash associated with moderate or severe herpes simplex, for which oral antiviral medication is indicated * Labial/facial herpes: Patients with at least 10 papulae or vesicles/pustules * Recurrent genital herpes: Patients with at least 5 papulae or vesicles/pustules on the genital organs or in the genital and circumanal region 2. Patients who can start receiving the study drug within 48 hours after onset of rash 3. Age: 20 years or older, but younger than 80 years
Exclusion criteria
1. Patients who are not expected to have an adequate response to oral antiviral medication 2. An extreme decline in immune function 3. Presence of serious complications 4. Patients found to meet any of the following conditions based on laboratory tests performed within 14 days before informed consent: * AST or ALT ≥ 2.5 x upper limit of normal * Platelet count \< lower limit of normal * Serum creatinine ≥ 1.5 mg/dL * Creatinine clearance \< 30 mL/min 5. Current or previous history of malignant tumor within 5 years before informed consent 6. Diagnosis of autoimmune disease 7. Evidence of bone marrow suppression
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Healing by Day 8 | 8days | The percentage of participants achieving lesion healing by Day 8 of study treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Healing | 29days | The criteria for determining healing are as follows: 1. A condition where all erythematous and papular lesions, vesicular and pustular lesions, and erosive and ulcerative lesions have been resolved, and either the complete resolution of crusts or the complete epithelialization beneath any remaining crusts has been achieved. 2. In participants where no crust has formed, a condition characterized by the epithelialization of erosions/ulcers formation in mucosal lesions and potentially other affected areas. 3. In participants where no vesicles or pustules have formed, a condition characterized by the complete resolution of all erythematous and papular lesions |
| Time to Complete Crusting | 29days | The criteria for complete crust formation are outlined as follows: 1. A condition where all erythematous and papular lesions, vesicular and pustular lesions, and erosive and ulcerative lesions have been resolved, and all rashes are crusted (epithelialization beneath is not required). 2. In participants where no crust has formed, a condition characterized by the epithelialization of erosions/ulcers formation in mucosal lesions and potentially other affected areas. 3. In participants where no vesicles or pustules have formed, a condition characterized by the complete resolution of all erythematous and papular lesions. |
| Time to Virus Disappearance | 29days | The day of viral disappearance is the first day on which the results of viral isolation continuously show 'HSV negative' until the final implementation day. The negative means that the results of the isolation and culture are negative, or the isolation and culture has not been performed due to complete crusting or healing of the lesion site. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ASP2151 200mg once daily | 307 |
| ASP2151 Placebo ASP2151 placebo once daily | 154 |
| Total | 461 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Clinical laboratory value is ineligible on day 1 | 10 | 6 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Physician Decision | 2 | 3 |
| Overall Study | Protocol Violation | 16 | 5 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | ASP2151 | ASP2151 Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 7 Participants | 27 Participants |
| Age, Categorical Between 18 and 65 years | 287 Participants | 147 Participants | 434 Participants |
| Age, Continuous | 40.4 years STANDARD_DEVIATION 12.9 | 40.5 years STANDARD_DEVIATION 13.5 | 40.4 years STANDARD_DEVIATION 13.1 |
| Disease type Labial/facial herpes | 264 Participants | 133 Participants | 397 Participants |
| Disease type Recurrent genital herpes | 43 Participants | 21 Participants | 64 Participants |
| Region of Enrollment Japan | 307 participants | 154 participants | 461 participants |
| Sex: Female, Male Female | 219 Participants | 107 Participants | 326 Participants |
| Sex: Female, Male Male | 88 Participants | 47 Participants | 135 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 128 / 309 | 59 / 157 |
| other Total, other adverse events | 69 / 309 | 29 / 157 |
| serious Total, serious adverse events | 0 / 309 | 0 / 157 |
Outcome results
Primary
Percentage of Participants With Healing by Day 8
The percentage of participants achieving lesion healing by Day 8 of study treatment
Time frame: 8days
Population: The full analysis set (FAS). The FAS was defined as patients who were diagnosed with labial/facial herpes or recurrent genital herpes at the time of case registration, subsequently received the study drug at least once, and had any efficacy variable measured, except for those found not to have herpes simplex after study drug administration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ASP2151 | Percentage of Participants With Healing by Day 8 | 66.4 Percentage of Participants |
| ASP2151 Placebo | Percentage of Participants With Healing by Day 8 | 69.5 Percentage of Participants |
Comparison: The superiority of ASP2151 200mg to ASP2151 placebo was assessed by Mantel-Haenszel method, adjusted by disease type (labial/facial herpes and recurrent genital herpes) .p-value: 0.5086Mantel Haenszel
Secondary
Time to Complete Crusting
The criteria for complete crust formation are outlined as follows: 1. A condition where all erythematous and papular lesions, vesicular and pustular lesions, and erosive and ulcerative lesions have been resolved, and all rashes are crusted (epithelialization beneath is not required). 2. In participants where no crust has formed, a condition characterized by the epithelialization of erosions/ulcers formation in mucosal lesions and potentially other affected areas. 3. In participants where no vesicles or pustules have formed, a condition characterized by the complete resolution of all erythematous and papular lesions.
Time frame: 29days
Population: The full analysis set (FAS). The FAS was defined as patients who were diagnosed with labial/facial herpes or recurrent genital herpes at the time of case registration, subsequently received the study drug at least once, and had any efficacy variable measured, except for those found not to have herpes simplex after study drug administration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ASP2151 | Time to Complete Crusting | 6 day |
| ASP2151 Placebo | Time to Complete Crusting | 6 day |
Secondary
Time to Healing
The criteria for determining healing are as follows: 1. A condition where all erythematous and papular lesions, vesicular and pustular lesions, and erosive and ulcerative lesions have been resolved, and either the complete resolution of crusts or the complete epithelialization beneath any remaining crusts has been achieved. 2. In participants where no crust has formed, a condition characterized by the epithelialization of erosions/ulcers formation in mucosal lesions and potentially other affected areas. 3. In participants where no vesicles or pustules have formed, a condition characterized by the complete resolution of all erythematous and papular lesions
Time frame: 29days
Population: The full analysis set (FAS). The FAS was defined as patients who were diagnosed with labial/facial herpes or recurrent genital herpes at the time of case registration, subsequently received the study drug at least once, and had any efficacy variable measured, except for those found not to have herpes simplex after study drug administration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ASP2151 | Time to Healing | 8 day |
| ASP2151 Placebo | Time to Healing | 8 day |
Secondary
Time to Virus Disappearance
The day of viral disappearance is the first day on which the results of viral isolation continuously show 'HSV negative' until the final implementation day. The negative means that the results of the isolation and culture are negative, or the isolation and culture has not been performed due to complete crusting or healing of the lesion site.
Time frame: 29days
Population: The full analysis set (FAS). The FAS was defined as patients who were diagnosed with labial/facial herpes or recurrent genital herpes at the time of case registration, subsequently received the study drug at least once, and had any efficacy variable measured, except for those found not to have herpes simplex after study drug administration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ASP2151 | Time to Virus Disappearance | 4 day |
| ASP2151 Placebo | Time to Virus Disappearance | 5 day |