A Study to Evaluate Efficacy and Safety of Abatacept in Participants of Pemphigus Vulgaris (PV)
A Crossover, Randomized and Multi-center Study to Evaluate the Efficacy and Safety of Abatacept Versus Mycophenolate Mofetil (MMF) in Treatment of PV
1 other identifier
interventional
60
1 country
1
Brief Summary
Pemphigus vulgaris (PV) is a rare, chronic, debilitating, and potentially life-threatening autoimmune disorder that is characterized by mucocutaneous blisters.Abatacept is a biologic drug that belongs to the class of T-cell co-stimulation modulators and is used for the treatment of autoimmune diseases.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_4
Started Feb 2021
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2021
CompletedFirst Submitted
Initial submission to the registry
February 25, 2022
CompletedFirst Posted
Study publicly available on registry
March 31, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
September 30, 2022
CompletedMarch 31, 2022
March 1, 2022
1.6 years
February 25, 2022
March 20, 2022
Conditions
Outcome Measures
Primary Outcomes (2)
Percentage of Participants Who Achieved Sustained Complete Remission, Evaluated by the Pemphigus Disease Area Index (PDAI) Activity Score
PADAI and ABSIS was proposed by the German Blistering Disease Group in 2007 which was accepted as the most sensitive and reliable systems for evaluation of pemphigus severity. PADAI was developed by the International Pemphigus Definitions Group in 2009
24 Weeks
Percentage of Participants Who Achieved Sustained Complete Remission, Evaluated byAutoimmune bullous skin disorder intensity score (ABSIS)
PADAI and ABSIS was proposed by the German Blistering Disease Group in 2007 which was accepted as the most sensitive and reliable systems for evaluation of pemphigus severity. PADAI was developed by the International Pemphigus Definitions Group in 2009
24 Weeks
Secondary Outcomes (6)
Cumulative Oral Corticosteroid Dose
From 12th, 24th, 36th and 52th Week
Ulcer Severity Score (USS) for the assessment of skin, oral ulcer improvement
From baseline up to 4th, 8th,12th, 24th, 36th and 52th Week
Physician global assessment (PGA)
From baseline up to 4th, 8th,12th, 24th, 36th and 52th Week
Autoimmune bullous disease quality of life (ABQoL)
From baseline up to 4th, 8th,12th, 24th, 36th and 52th Week
Anti-desmoglein 1 (anti-Dsg1) and anti-Dsg3 autoantibody titers
From Baseline up to 12th, 24th and 52th Week
- +1 more secondary outcomes
Study Arms (2)
Abatacept
EXPERIMENTALSubject received subcutaneous administration of abatacept 125 mg once every week through the 52 week double blind period.
Mycophenolate mofetil
ACTIVE COMPARATORSubject received subcutaneous administration of matching placebo of abatacept once a weeks through the 24 week double blind period. A washout period of MMF for 4 weeks (24 th-28th week) is used to ensure data integrity. Subsequently,subject were administered subcutaneous administration of abatacept 125 mg once every week through the 28-52 week open label period.
Interventions
Abatacept (Orencia) was provided in prefilled glass syringes initial syringes contained 0.6ml (60mg) of concentration 100 mg/m: drug product subsequently modified to 0.4 mL (20mg) concentration (50mg/ML) drug product. Combined with standard of care prednisone 10-40mg qd
MMF will be administered at a starting dose of 1000 milligrams (mg) Q12H and the dose will be tapered to achieve a goal of 0.5-1.0 gram (gm) Q12H. Combined with standard of care prednisone 10-40mg qd through 52 weeks.
Eligibility Criteria
You may qualify if:
- Adults (18 through 80 years of age) with clinically-documented diagnosis of PV for \>2 months and \<10 years.
- History of biopsy consistent with PV (Hematoxylin and Eosin staining and direct immunofluorescence). Confirmed diagnosis of PV within the previous 24 months, based on the presence of histological features of acantholysis via skin or mucosal biopsy and one of the following: tissue bound immunoglobulin G (IgG) antibodies by direct immunofluorescence on the surface of affected epithelium or serological detection of serum desmoglein-3 (DSg3) autoantibodies against epithelial cell surface either by indirect immunofluorescence microscopy or by enzyme-linked immunosorbent assay.
- At least 1 previous episode of a failed steroid taper (ie, disease flare/relapse) at a prednisone/prednisolone dose \>10 mg/day. The following criteria must have been met as evidence of disease severity at the time of the failed steroid taper: a) A Pemphigus Severity of Clinical Disease score of moderate (2) or severe (3) (may be historical/retrospective assessment). b) Required a treatment change at the time of the failed steroid taper of at least one of the following: i) A steroid increase to \>=20 mg/day OR ii) The addition of immunosuppressive/immunomodulatory agent/treatment OR iii) A dose increase of immunosuppressive/immunomodulatory agent/treatment
- Screening anti-Dsg antibodies consistent with a diagnosis of PV (ie, elevated antiDsg3 antibodies).
- Has initiated and received a stable dose of prednisone/prednisolone from a minimum of 20 mg/day (example: 0.25 mg/kg/day for an 80 kg person) up to a maximum of 120 mg/day or 1.5 mg/kg/day (whichever is higher) for \>=2 weeks prior to randomization.
- Has exhibited PV disease control, defined as no new lesions for \>=2 weeks. A female subject is eligible to enter the study if she: Is of non-child bearing potential, who 7. is either surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or post-hysterectomy) or is postmenopausal without menses for \>2 years. Women who are \<2 years postmenopausal are required to have menopausal status confirmed by follicle-stimulating hormone (FSH) and estradiol levels at the screening evaluation. If FSH and estradiol levels do not provide confirmation of menopause, subject will be considered to be of childbearing potential.
You may not qualify if:
- Diagnosis of pemphigus foliaceus, paraneoplastic pemphigus, or other autoimmune blistering disease (other than pemphigus vulgaris).
- Past or current history of hypersensitivity to components of the investigational product or medically significant adverse effects (including allergic reactions) from cetirizine (or antihistamine equivalent) or paracetamol/acetaminophen.
- Prior treatment with rituximab without achieving disease control within 6 months of initiating rituximab dosing.
- Prior treatment with immunosuppressant or immunomodulation agents within the protocol specified periods
- Evidence or history of clinically significant infections
- Past or current malignancy, except for cervical carcinoma Stage 1B or less, noninvasive basal cell and squamous cell skin carcinoma and cancer diagnoses with a duration of complete response (remission) \>5 years
- Significant concurrent, uncontrolled medical condition that could affect the subject's safety, impair the subject's reliable participation in the study, impair the evaluation of endpoints, or necessitate the use of medication not allowed by the protocol. This includes subjects who require any systemic steroid treatment for a concurrent medical condition (other than pemphigus vulgaris).
- Use of an investigational drug or other experimental therapy within 4 weeks, 5 pharmacokinetic half-lives, or the duration of biological effect (whichever is longer) prior to Screening.
- Electrocardiogram (ECG) showing a clinically significant abnormality or showing a QTc interval ≥450 msec (≥480 msec for subjects with a bundle branch block)
- Woman who is breastfeeding.
- Positive test results for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) serology at screening
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Tongji Hospitallead
- Wuhan Central Hospitalcollaborator
- Wuhan Hospital of Traditional Chinese Medicinecollaborator
Study Sites (1)
Tongji Hospital
Wuhan, Hubei, 430030, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
AIHUA DU, M.D
Tongji Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- CARE PROVIDER, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
February 25, 2022
First Posted
March 31, 2022
Study Start
February 1, 2021
Primary Completion
September 1, 2022
Study Completion
September 30, 2022
Last Updated
March 31, 2022
Record last verified: 2022-03
Data Sharing
- IPD Sharing
- Will not share