Pemphigus Vulgaris (PV)
Conditions
Brief summary
This study was designed to assess the efficacy and safety of CellCept (1 g or 1.5 g orally twice daily for 52 weeks) in patients with pemphigus vulgaris receiving prednisone or other corticosteroids. During the study, patients had their corticosteroid dose gradually reduced if they responded to treatment. The anticipated time on study treatment was 12 months, and the target sample size was \<100 individuals.
Interventions
DRUGMycophenolate Mofetil 2 g/Day
Mycophenolate mofetil 500 mg tablets; 4 tablets twice daily for 52 weeks
DRUGMycophenolate Mofetil (MMF) 3 g/Day
Mycophenolate mofetil 500 mg tablets; 6 tablets twice daily for 52 weeks
DRUGPlacebo
Placebo for MMF 2 g/day group: 4 tablets orally twice daily for 52 weeks; placebo for MMF 3 g/day group: 6 tablets orally twice daily for 52 weeks
Sponsors
Aspreva Pharmaceuticals
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients 18 to 70 years of age * Diagnosis of mild to moderate pemphigus vulgaris within the past 12 months, requiring high dose corticosteroids
Exclusion criteria
* Female patients who are pregnant, breastfeeding, or lactating * Regularly scheduled plasma exchange (PE) or intravenous immunoglobulin (IVIG) treatment, or PE or IVIG treatment within 8 weeks prior to randomization * CellCept or other immunosuppressive therapy, except corticosteroids, exceeding 2 weeks total duration and within 8 weeks prior to randomization * Use of PV therapies other than those noted above, within 4 weeks prior to randomization * Use of topical corticosteroids within 2 weeks prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Achieving Responder Status at Week 52 | 52 weeks | The proportion of subjects achieving responder status (defined as no new persistent lesions and prednisone dose of not more than 10 mg/day from Week 48 until study termination at Week 52) in the two active treatment groups combined (2 g/day and 3 g/day mycophenolate mofetil) compared with the placebo group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Initial Response | up to 52 weeks | Time to initial response defined as the time that the subject first demonstrated responder status (defined as no new persistent lesions and prednisone dose of not more than 10 mg/day from Week 48 until study termination at Week 52) |
| Time to Sustained Response | up to 52 weeks | Time to sustained response is defined as the week the subject first demonstrates both of the conditions of responder status provided the conditions are maintained through to study termination at Week 52. If a subject does not have a sustained response, time to sustained response is censored on the last day of the study. |
| Duration of Prednisone Maintenance Dosing | 52 weeks | The duration of prednisone maintenance dosing was defined as the number of days that subjects maintained a prednisone dose of not more than 10 mg/day in the absence of new persistent lesions. |
Countries
Canada, Germany, Israel, Switzerland, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo for Mycophenolate Mofetil (MMF) 2 g/day group: 4 tablets orally twice daily for 52 weeks; placebo for MMF 3 g/day group: 6 tablets orally twice daily for 52 weeks | 36 |
| MMF 2 g/Day Mycophenolate mofetil (MMF) 500 mg tablets; 4 tablets twice daily for 52 weeks | 21 |
| MMF 3 g/Day Mycophenolate mofetil (MMF) 500 mg tablets; 6 tablets twice daily for 52 weeks | 37 |
| Total | 94 |
Baseline characteristics
| Characteristic | Placebo | MMF 2 g/Day | MMF 3 g/Day | Total |
|---|---|---|---|---|
| Age Continuous | 45.8 years STANDARD_DEVIATION 12.18 | 41.0 years STANDARD_DEVIATION 15.59 | 44.8 years STANDARD_DEVIATION 13.47 | 44.33 years STANDARD_DEVIATION 13.45 |
| Sex: Female, Male Female | 24 Participants | 14 Participants | 18 Participants | 56 Participants |
| Sex: Female, Male Male | 12 Participants | 7 Participants | 19 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 31 / 36 | 20 / 21 | 32 / 37 |
| serious Total, serious adverse events | 4 / 36 | 1 / 21 | 3 / 37 |
Outcome results
Primary
Percentage of Patients Achieving Responder Status at Week 52
The proportion of subjects achieving responder status (defined as no new persistent lesions and prednisone dose of not more than 10 mg/day from Week 48 until study termination at Week 52) in the two active treatment groups combined (2 g/day and 3 g/day mycophenolate mofetil) compared with the placebo group
Time frame: 52 weeks
Population: Intent-to-treat population. Analysis population (AP): Placebo = 36; MMF 2 g/day or 3 g/day = 58.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients Achieving Responder Status at Week 52 | 63.9 Percentage of Participants |
| MMF 2 g/Day and MMF 3 g/Day Groups Combined | Percentage of Patients Achieving Responder Status at Week 52 | 69.0 Percentage of Participants |
p-value: 0.655897.5% CI: [-17.4, 27.6]Fisher Exact
Secondary
Duration of Prednisone Maintenance Dosing
The duration of prednisone maintenance dosing was defined as the number of days that subjects maintained a prednisone dose of not more than 10 mg/day in the absence of new persistent lesions.
Time frame: 52 weeks
Population: Intent-to-treat population. Analysis population (AP): Placebo = 36; MMF 2 g/day = 21; MMF 3 g/day = 37; MMF Groups Combined (2 g/day or 3 g/day) = 58.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Duration of Prednisone Maintenance Dosing | 136.5 Days |
| MMF 2 g/Day and MMF 3 g/Day Groups Combined | Duration of Prednisone Maintenance Dosing | 186.0 Days |
| Mycophenolate Mofetil 2 g/Day | Duration of Prednisone Maintenance Dosing | 185.0 Days |
| Mycophenolate Mofetil 3 g/Day | Duration of Prednisone Maintenance Dosing | 187.0 Days |
Secondary
Time to Initial Response
Time to initial response defined as the time that the subject first demonstrated responder status (defined as no new persistent lesions and prednisone dose of not more than 10 mg/day from Week 48 until study termination at Week 52)
Time frame: up to 52 weeks
Population: Intent-to-treat population. Analysis population (AP): Placebo = 36, subjects censored = 7; MMF 2 g/day or 3 g/day = 58, subjects censored = 10.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Initial Response | 31.3 Weeks |
| MMF 2 g/Day and MMF 3 g/Day Groups Combined | Time to Initial Response | 24.1 Weeks |
Secondary
Time to Sustained Response
Time to sustained response is defined as the week the subject first demonstrates both of the conditions of responder status provided the conditions are maintained through to study termination at Week 52. If a subject does not have a sustained response, time to sustained response is censored on the last day of the study.
Time frame: up to 52 weeks
Population: Intent-to-treat population. Analysis population (AP): Placebo = 36, subjects censored = 20; MMF 2 g/day or 3 g/day = 58, subjects censored = 23.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Sustained Response | 46.0 Weeks |
| MMF 2 g/Day and MMF 3 g/Day Groups Combined | Time to Sustained Response | 32.1 Weeks |