Herpes Zoster
Conditions
Brief summary
To evaluate the efficacy and safety of ASP2151 (200 mg and 400 mg) in comparison with valaciclovir (VACV) 3000 mg in patients with herpes zoster.
Detailed description
A double-blind, randomized, parallel-group study will be conducted to evaluate the efficacy and safety of ASP2151 (200 mg and 400 mg) in comparison with valaciclovir (VACV) 3000 mg in patients with herpes zoster. The efficacy will be evaluated for the primary endpoint defined as, the proportion of subjects achieving cessation of new lesion formation by Day 4 of study treatment to demonstrate the non-inferiority of ASP2151 to VACV. The safety will be evaluated based on adverse events, laboratory tests, vital signs, and ECGs.
Interventions
DRUGASP2151
200 mg once daily or 400 mg once daily
DRUGvalaciclovir
1000 mg three times 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 who have a rash associated with herpes zoster, and who can start receiving the study drug within 72 hours after onset of the rash
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 \< 50 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 |
|---|---|---|
| The Percentage of Participants Achieving Cessation of New Lesion Formation by Day 4 of Study Treatment | 4days | The investigator assessed the Number of rashes (erythemas/papulae and vesicles/pustules). The new lesion formation was defined as the state in which the number of rashes is increasing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Cessation of New Lesion Formation | 29days | The investigator assessed the Number of rashes (erythemas/papulae and vesicles/pustules). The new lesion formation was defined as the state in which the number of rashes is increasing. |
| Time to Complete Crusting | 29days | We defined the following state as Complete crusting. 1. A condition where all lesions of erythemas/papulae, vesicles/pustules, and erosions/ulcers have disappeared, and all rashes are crusted (epithelialization of the base of crusts is not required). 2. In subjects with no formation of vesicles or pustules, a condition where all lesions of erythemas/papulae have disappeared. |
| Time to Healing | 29days | We defined the following state as Healing. 1. A condition where all lesions of erythemas/papulae, vesicles/pustules, and erosions/ulcers have disappeared, and complete disappearance of crusts or complete epithelialization of the base of crusts are considered to have been achieved. 2. In subjects with no formation of vesicles or pustules, a condition where all lesions of erythemas/papulae have disappeared |
| Time to Pain Resolution | 29days | Investigators assessed the pain using NRS. The date of pain resolution is defined as the first day when all NRS scores are rated as 2 or less, and such scores are continuously observed until Day 92 or discontinuation visit. |
| Time to Virus Disappearance | 29days | Virus desiappearance was defined as the participants who who reached virus-negative status according to the virus isolation and culture assay or whose samples were not available because of complete crusting or healing |
Countries
Japan
Participant flow
Recruitment details
The study was conducted at 106 sites in Japan from September 2013 to Jully 2015
Participants by arm
| Arm | Count |
|---|---|
| ASP2151(200 mg) once daily
ASP2151: 200 mg once daily or 400 mg once daily | 247 |
| ASP2151(400mg) once daily
ASP2151: 200 mg once daily or 400 mg once daily | 243 |
| Valaciclovir 1000 mg three times daily
valaciclovir: 1000 mg three times daily | 245 |
| Total | 735 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 2 |
| Overall Study | Clinical laboratory value | 2 | 6 | 6 |
| Overall Study | Lack of Efficacy | 5 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 2 | 3 |
| Overall Study | Platelet count below on day1 or 4 | 11 | 15 | 11 |
| Overall Study | Protocol Violation | 16 | 23 | 16 |
| Overall Study | Withdrawal by Subject | 7 | 7 | 5 |
Baseline characteristics
| Characteristic | ASP2151(200 mg) | ASP2151(400mg) | Valaciclovir | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 69 Participants | 69 Participants | 67 Participants | 205 Participants |
| Age, Categorical Between 18 and 65 years | 178 Participants | 174 Participants | 178 Participants | 530 Participants |
| Age, Continuous | 52.0 years STANDARD_DEVIATION 16.3 | 53.0 years STANDARD_DEVIATION 16.2 | 52.2 years STANDARD_DEVIATION 15.8 | 52.39 years STANDARD_DEVIATION 16.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 247 Participants | 243 Participants | 245 Participants | 735 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 247 Participants | 243 Participants | 245 Participants | 735 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 247 Participants | 243 Participants | 245 Participants | 735 Participants |
| Sex: Female, Male Female | 134 Participants | 144 Participants | 146 Participants | 424 Participants |
| Sex: Female, Male Male | 113 Participants | 99 Participants | 99 Participants | 311 Participants |
| Time from onset of rash to the first dose over 24 hours, within 48 hours | 92 Participants | 98 Participants | 91 Participants | 281 Participants |
| Time from onset of rash to the first dose over 48 hours, within 72 hours | 102 Participants | 89 Participants | 109 Participants | 300 Participants |
| Time from onset of rash to the first dose within 24 hours | 53 Participants | 56 Participants | 45 Participants | 154 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 252 | 0 / 249 | 0 / 249 |
| other Total, other adverse events | 62 / 252 | 64 / 249 | 65 / 249 |
| serious Total, serious adverse events | 1 / 252 | 1 / 249 | 3 / 249 |
Outcome results
Primary
The Percentage of Participants Achieving Cessation of New Lesion Formation by Day 4 of Study Treatment
The investigator assessed the Number of rashes (erythemas/papulae and vesicles/pustules). The new lesion formation was defined as the state in which the number of rashes is increasing.
Time frame: 4days
Population: The full analysis set(FAS).The FAS was defined as patients who were diagnosed with herpes zoster at the time of case registration, who subsequently received the study drugs, and had any efficacy variable measured.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ASP2151(200 mg) | The Percentage of Participants Achieving Cessation of New Lesion Formation by Day 4 of Study Treatment | 69.6 percentage of Participants |
| ASP2151(400mg) | The Percentage of Participants Achieving Cessation of New Lesion Formation by Day 4 of Study Treatment | 81.1 percentage of Participants |
| Valaciclovir | The Percentage of Participants Achieving Cessation of New Lesion Formation by Day 4 of Study Treatment | 75.1 percentage of Participants |
Comparison: The non-inferiority of each ASP2151 dose level versus valaciclovir was assessed stepwise using a closed testing procedure.First step analysis was performed in the ASP2151(400mg) once daily.p-value: 0.00000241Modified Farrington-Manning test
Comparison: The analysis was performed in the ASP2151(200 mg) once daily only when non-inferiority of the ASP2151(400 mg) 0nce daily to valaciclovir 1000 mg three times daily was assumed.p-value: 0.0688Modified Farrington-Manning test
Secondary
Time to Cessation of New Lesion Formation
The investigator assessed the Number of rashes (erythemas/papulae and vesicles/pustules). The new lesion formation was defined as the state in which the number of rashes is increasing.
Time frame: 29days
Population: The full analysis set(FAS).The FAS was defined as patients who were diagnosed with herpes zoster at the time of case registration, who subsequently received the study drugs, and had any efficacy variable measured.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ASP2151(200 mg) | Time to Cessation of New Lesion Formation | 4 days |
| ASP2151(400mg) | Time to Cessation of New Lesion Formation | 4 days |
| Valaciclovir | Time to Cessation of New Lesion Formation | 4 days |
Secondary
Time to Complete Crusting
We defined the following state as Complete crusting. 1. A condition where all lesions of erythemas/papulae, vesicles/pustules, and erosions/ulcers have disappeared, and all rashes are crusted (epithelialization of the base of crusts is not required). 2. In subjects with no formation of vesicles or pustules, a condition where all lesions of erythemas/papulae have disappeared.
Time frame: 29days
Population: The full analysis set(FAS).The FAS was defined as patients who were diagnosed with herpes zoster at the time of case registration, who subsequently received the study drugs, and had any efficacy variable measured.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ASP2151(200 mg) | Time to Complete Crusting | 8 days |
| ASP2151(400mg) | Time to Complete Crusting | 9 days |
| Valaciclovir | Time to Complete Crusting | 8 days |
Secondary
Time to Healing
We defined the following state as Healing. 1. A condition where all lesions of erythemas/papulae, vesicles/pustules, and erosions/ulcers have disappeared, and complete disappearance of crusts or complete epithelialization of the base of crusts are considered to have been achieved. 2. In subjects with no formation of vesicles or pustules, a condition where all lesions of erythemas/papulae have disappeared
Time frame: 29days
Population: The full analysis set(FAS).The FAS was defined as patients who were diagnosed with herpes zoster at the time of case registration, who subsequently received the study drugs, and had any efficacy variable measured.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ASP2151(200 mg) | Time to Healing | 11 days |
| ASP2151(400mg) | Time to Healing | 11 days |
| Valaciclovir | Time to Healing | 11 days |
Secondary
Time to Pain Resolution
Investigators assessed the pain using NRS. The date of pain resolution is defined as the first day when all NRS scores are rated as 2 or less, and such scores are continuously observed until Day 92 or discontinuation visit.
Time frame: 29days
Population: The full analysis set(FAS).The FAS was defined as patients who were diagnosed with herpes zoster at the time of case registration, who subsequently received the study drugs, and had any efficacy variable measured.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ASP2151(200 mg) | Time to Pain Resolution | 9 days |
| ASP2151(400mg) | Time to Pain Resolution | 10 days |
| Valaciclovir | Time to Pain Resolution | 10 days |
Secondary
Time to Virus Disappearance
Virus desiappearance was defined as the participants who who reached virus-negative status according to the virus isolation and culture assay or whose samples were not available because of complete crusting or healing
Time frame: 29days
Population: The full analysis set(FAS).The FAS was defined as patients who were diagnosed with herpes zoster at the time of case registration, who subsequently received the study drugs, and had any efficacy variable measured.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ASP2151(200 mg) | Time to Virus Disappearance | 4 days |
| ASP2151(400mg) | Time to Virus Disappearance | 5 days |
| Valaciclovir | Time to Virus Disappearance | 4 days |