Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05303272
Other study ID # TJRH2021109
Secondary ID
Status Recruiting
Phase Phase 4
First received
Last updated
Start date February 1, 2021
Est. completion date September 30, 2022

Study information

Verified date March 2022
Source Tongji Hospital
Contact YIKAI YU
Phone +1 484-995-5917
Email yuyikai@163.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

The background therapy is based on prednisolone administration. PV is a rare disorder, therefore this study is designed as a crossover that may require fewer patients than a parallel study. The study enrolled participants with moderate-to-severely active PV requiring ≥ 50 milligrams per day (mg/day) oral prednisone or equivalent. The purpose of this study was to evaluate the efficacy, tolerability, and safety of abatacept injection for subcutaneous use (abatacept SC) 150 mg administered once in a week in subjects with PV. It was anticipated that with sustained immune suppression in the presence of abatacept SC that clinical remission of the disease would be improved.


Recruitment information / eligibility

Status Recruiting
Enrollment 60
Est. completion date September 30, 2022
Est. primary completion date September 1, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility Inclusion Criteria: 1. Adults (18 through 80 years of age) with clinically-documented diagnosis of PV for >2 months and <10 years. 2. 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. 3. 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 4. Screening anti-Dsg antibodies consistent with a diagnosis of PV (ie, elevated antiDsg3 antibodies). 5. 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. 6. 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. Exclusion Criteria: 1. Diagnosis of pemphigus foliaceus, paraneoplastic pemphigus, or other autoimmune blistering disease (other than pemphigus vulgaris). 2. 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. 3. Prior treatment with rituximab without achieving disease control within 6 months of initiating rituximab dosing. 4. Prior treatment with immunosuppressant or immunomodulation agents within the protocol specified periods 5. Evidence or history of clinically significant infections 6. 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 7. 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). 8. 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. 9. Electrocardiogram (ECG) showing a clinically significant abnormality or showing a QTc interval =450 msec (=480 msec for subjects with a bundle branch block) 10. Woman who is breastfeeding. 11. Positive test results for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) serology at screening

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Abatacept Prefilled Syringe
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
Mycophenolate Mofetil 500Mg Tab
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.

Locations

Country Name City State
China Tongji Hospital Wuhan Hubei

Sponsors (3)

Lead Sponsor Collaborator
Tongji Hospital Wuhan Central Hospital, Wuhan Hospital of Traditional Chinese Medicine

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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 Cumulative Oral Corticosteroid Dose Calculate the Cumulative Oral Corticosteroid Dose during 52 week From 12th, 24th, 36th and 52th Week
Secondary Ulcer Severity Score (USS) for the assessment of skin, oral ulcer improvement The USS incorporates six ulcer characteristics: number, size, duration, ulcer-free period, site, and pain. This scoring template may be of value to future studies assessing treatment efficacy. From baseline up to 4th, 8th,12th, 24th, 36th and 52th Week
Secondary Physician global assessment (PGA) Physician global assessment was assessed by an individual researcher From baseline up to 4th, 8th,12th, 24th, 36th and 52th Week
Secondary Autoimmune bullous disease quality of life (ABQoL) Total ABQoL scores range from 0 to 30 with higher DLQI scores reflecting greater impairment in a participant's health-related quality of life. The ABQoL score is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. The measure type mean is the estimated mean from adjusted MMRM. From baseline up to 4th, 8th,12th, 24th, 36th and 52th Week
Secondary Anti-desmoglein 1 (anti-Dsg1) and anti-Dsg3 autoantibody titers anti-Dsg1 and anti-Dsg3 will be performed using ELISA From Baseline up to 12th, 24th and 52th Week
Secondary Change From Baseline for CD19+ B Cell Count CD19+ B cell count will be performed using Flow Cytometry From Baseline up to 12th, 24th and 52th Week
See also
  Status Clinical Trial Phase
Recruiting NCT04422912 - A Phase 1/2, Open-label, Safety and Dosing Study of Autologous CART Cells (Desmoglein 3 Chimeric Autoantibody Receptor T Cells [DSG3-CAART] or CD19-specific Chimeric Antigen Receptor T Cells [CABA-201]) in Subjects With Active, Pemphigus Vulgaris (RESET-PV) Phase 1
Recruiting NCT05635266 - Tissue Repository Providing Annotated Biospecimens for Approved Investigator-directed Biomedical Research Initiatives
Recruiting NCT04117529 - Phenotypic and Functional Characterisation of Human B-cell Response in Pemphigus N/A
Completed NCT03334058 - A Study to Evaluate the Safety, PD, PK and Efficacy of ARGX-113 in Patients With Pemphigus Phase 2
Terminated NCT03239470 - Polyclonal Regulatory T Cells (PolyTregs) for Pemphigus Phase 1
Completed NCT00606749 - Use of KC706 for the Treatment of Pemphigus Vulgaris Phase 2
Terminated NCT00429533 - Efficacy of Dapsone as a Steroid Sparing Agent in Pemphigus Vulgaris Phase 2
Recruiting NCT05594472 - Ozonated Olive Oil in Treatment of Pemphigus Vulgaris and Bullous Pemphigoid Phase 3
Completed NCT02383589 - A Study to Evaluate the Efficacy and Safety of Rituximab Versus Mycophenolate Mofetil (MMF) in Participants With Pemphigus Vulgaris (PV) Phase 3
Withdrawn NCT03780166 - A Study of the Safety and Tolerability of INCB050465 in Pemphigus Vulgaris Phase 2
Recruiting NCT04096222 - Comparative Analysis of the Th17 Cellular Response in Active and Inactive Pemphigus Vulgaris Patients
Not yet recruiting NCT03177213 - Serum IL-21 Levels in Patients With Pemphigus Vulgaris N/A
Completed NCT00135720 - Study of Etanercept (Enbrel) in the Treatment of Pemphigus Vulgaris Phase 2
Completed NCT00063752 - Safety Study of PI-0824 to Treat Pemphigus Vulgaris Phase 1
Terminated NCT03075904 - A Safety and Dose-Finding Study of SYNT001 in Subjects With Pemphigus (Vulgaris or Foliaceus) Phase 1/Phase 2
Terminated NCT04598477 - A Study to Assess the Long-term Safety and Efficacy of a Subcutaneous Formulation of Efgartigimod PH20 SC in Adults With Pemphigus (Vulgaris or Foliaceus) Phase 3
Completed NCT02704429 - A Study of PRN1008 in Adult Patients With Pemphigus Vulgaris Phase 2
Completed NCT00626678 - Azathioprine Versus Placebo in Pemphigus Vulgaris Treated With Prednisolone Phase 2
Active, not recruiting NCT05338112 - Role of Tzanck Smear in Determining Pemphigus Vulgaris Disease Activity
Completed NCT06167408 - Identifying Factors Influencing In-Hospital Relapse in Pemphigus Patients