A Study to Evaluate the Safety, PD, PK and Efficacy of ARGX-113 in Patients With Pemphigus
Primary Purpose
Pemphigus Vulgaris, Pemphigus Foliaceus
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ARGX-113
Sponsored by
About this trial
This is an interventional treatment trial for Pemphigus Vulgaris
Eligibility Criteria
Inclusion Criteria:
- Male or female patients aged ≥ 18 years.
- Clinical diagnosis of PV or PF, that has been confirmed by positive direct immunofluorescence and by positive indirect immunofluorescence and/or ELISA.
- Mild to moderate disease severity (PDAI < 45).
- Newly diagnosed patients or relapsing patients off therapy with or without a first course of prednisone of maximum 4 weeks, and for whom an initial period of ARGX-113 monotherapy is judged clinically acceptable; or newly diagnosed patients or relapsing patients off therapy on a first course of oral prednisone at stable dose for at least 2 weeks and for whom ARGX-113 monotherapy is considered not clinically acceptable; or patients who relapse despite oral prednisone at tapered dose +/- a conventional immunosuppressant (e.g. azathioprine, mycophenolate mofetil).
- Identified serum levels of autoantibodies directed against Dsg 3 and/or Dsg-1 antigens at screening, using indirect immunofluorescence or ELISA.
- Ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), and comply with the study protocol procedures (including required study visits).
Exclusion Criteria:
- Pregnant and lactating women, and those intending to become pregnant during the study or within 90 days after the last dosing. Women of childbearing potential should have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline, prior to administration of IMP.
- Male patients who are sexually active that do not intend to use effective methods of contraception during the study or within 90 days after the last dosing.
- Confirmed diagnosis of paraneoplastic pemphigus, drug-induced pemphigus or any other non-PV/non-PF autoimmune blistering disease.
- History of refractory disease to active third line therapy (e.g. intravenous polyvalent human immunoglobulins [IVIg], rituximab, plasma exchange/ immunoadsorption).
- Use of therapies other than oral prednisone and conventional immunosuppressants, that can interfere in the clinical course of the disease (e.g. intravenous [IV] prednisolone bolus, dapsone, sulfasalazine, tetracyclines, nicotinamide, plasmapheresis/ plasma exchange, immunoadsorption and IVIg) within 2 months prior to Baseline visit.
- Use of rituximab and other CD20 target biologics within 6 months prior to Baseline visit.
- History of anaphylactic reaction, or a known hypersensitivity reaction to one of the components of the IMP.
- History of vaccination within the last 4 weeks prior to Baseline visit, or with a planned vaccination during the study, with the exception of seasonal vaccination (e.g. influenza vaccine).
- Recent serious infection (i.e., requiring injectable antimicrobial therapy or hospitalization) within the 8 weeks prior to Baseline visit.
- Known active or chronic viral infection with hepatitis B virus (HBV); refer to the Centers for Disease Control and Prevention (CDC) guidelines.
- Known seropositive or active infection with hepatitis C virus (HCV).
- Known history of or known viral infection with human immunodeficiency virus (HIV 1 and 2 antibodies).
- Body Mass Index (BMI) at Screening > 35,0 kg/m2.
- Clinical evidence of significant active, unstable or uncontrolled concomitant disease (e.g. cardiovascular, pulmonary, hematologic, gastrointestinal, endocrinological and metabolic, hepatic, renal, neurologic, malignancy, infectious diseases, coagulopathies, other autoimmune disease) or condition (lack of peripheral venous access, recent major surgery, etc), which, in the opinion of the investigator, puts the patient at undue risk or may affect the interpretation of the results.
- Patients in general health condition not allowing study participation (Karnofsky index < 60%; see Appendix 14.2).
At Screening, have clinically significant laboratory abnormalities as below:
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN)
- Total serum bilirubin of > 1.5 x ULN (except for Grade 1 hyperbilirubinemia as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), due solely to a documented medical diagnosis of Gilbert's syndrome)
- Serum creatinine of > 1.5 mg/dL or creatinine clearance < 50 mL/min (using the Chronic Kidney Disease Epidemiology Creatinine formula)
- Hemoglobin (Hb) ≤ 9 g/dL
- International normalized ratio (INR) > 1.5 or activated partial thromboplastin time (aPTT) > 1.5 x ULN
- Total immunoglobulin G (IgG) level < 6 g/L
- Presence of > 1 + proteinuria dipstick
- Patient having participated in another interventional study within the last 3 months prior to Baseline visit.
Sites / Locations
- University of Lübeck and UKSH, Department of Dermatology and Lübeck Institute of Experimental Dermatology
- Clinic of Dermatology and Allergology - Philipps University Marburg
- University of Debrecen Medical Center Department of Dermatology
- University of Pécs Clinical Center , Department of Dermatology, Venerology and Oncodermatology
- University of Szeged Faculty of Medicine Albert Szent-Györgyi Medical Center Department of Dermatology and Allergology
- HaEmek Medical center, Dermatology Department
- Department of Dermatology, The Chaim Sheba Medical Center
- Department of dermatology, The Tel Aviv Sourasky Medical Center
- Dermopathic Institute of the Immaculate - Foundation "Luigi Maria Monti"
- Foundation Policlinico A. Gemelli - Dermatology Department
- National Medical University named after O.O.Bohomolets, Department of Dermatology and Venereology based on Oleksandrivska Clinical Hospital of Kyiv City, Department of Dermatology
- Municipal Institution "Zaporizhzhya Regional Dermatology and Venereology Clinical Dispensary" of Zaporizhzhya Regional Council
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ARGX-113
Arm Description
Outcomes
Primary Outcome Measures
Safety and tolerability as measured by the incidence and severity of treatment-emergent (serious) adverse events over the study.
Secondary Outcome Measures
Evaluation of serum levels of total IgG and subtypes (IgG1, IgG2, IgG3, IgG4)
Evaluation of serum levels of anti Dsg-1 and -3 autoantibodies
Pemphigus Disease Area Index (PDAI)
The score has a range from 0 to 263, the higher the score, the more severe the disease.
Time to disease control (DC), control being defined as the absence of new lesions and established lesions beginning to heal
Time until relapse, relapse being defined as the appearance of 3 or more new lesions a month that do not heal spontaneously within 1 week, or as the extension of established lesions
Pharmacokinetic parameters of ARGX 113: Tmax
Pharmacokinetic parameters of ARGX 113: Cmax
Incidence of anti-drug antibodies (ADA) to ARGX 113
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03334058
Brief Title
A Study to Evaluate the Safety, PD, PK and Efficacy of ARGX-113 in Patients With Pemphigus
Official Title
An Open-label, Non-controlled, Phase II Study to Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, Efficacy and Conditions of Use of ARGX-113 in Patients With Mild to Moderate Pemphigus (Vulgaris and Foliaceus)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
October 18, 2017 (Actual)
Primary Completion Date
October 28, 2020 (Actual)
Study Completion Date
October 28, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
argenx
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The proposed study is an open-label, non-controlled, adaptive-design Phase II study to evaluate the safety, pharmacodynamics, pharmacokinetics, efficacy, and conditions of use (dosage, frequency of administration at maintenance) of ARGX-113 in patients with mild to moderate Pemphigus (Vulgaris or Foliaceus), either newly diagnosed or relapsing.
The total study duration for each patient is less than 6 months. It consists of a Screening period, an Induction, a maintenance treatment period followed by a treatment-free Follow-up (FU) period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pemphigus Vulgaris, Pemphigus Foliaceus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ARGX-113
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
ARGX-113
Intervention Description
human IgG1-derived Fc fragment that binds to human neonatal Fc receptor (FcRn)
Primary Outcome Measure Information:
Title
Safety and tolerability as measured by the incidence and severity of treatment-emergent (serious) adverse events over the study.
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
Evaluation of serum levels of total IgG and subtypes (IgG1, IgG2, IgG3, IgG4)
Time Frame
Up to 6 months
Title
Evaluation of serum levels of anti Dsg-1 and -3 autoantibodies
Time Frame
Up to 6 months
Title
Pemphigus Disease Area Index (PDAI)
Description
The score has a range from 0 to 263, the higher the score, the more severe the disease.
Time Frame
Up to 6 months
Title
Time to disease control (DC), control being defined as the absence of new lesions and established lesions beginning to heal
Time Frame
Up to 6 months
Title
Time until relapse, relapse being defined as the appearance of 3 or more new lesions a month that do not heal spontaneously within 1 week, or as the extension of established lesions
Time Frame
Up to 6 months
Title
Pharmacokinetic parameters of ARGX 113: Tmax
Time Frame
Up to 6 months
Title
Pharmacokinetic parameters of ARGX 113: Cmax
Time Frame
Up to 6 months
Title
Incidence of anti-drug antibodies (ADA) to ARGX 113
Time Frame
Up to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients aged ≥ 18 years.
Clinical diagnosis of PV or PF, that has been confirmed by positive direct immunofluorescence and by positive indirect immunofluorescence and/or ELISA.
Mild to moderate disease severity (PDAI < 45).
Newly diagnosed patients or relapsing patients off therapy with or without a first course of prednisone of maximum 4 weeks, and for whom an initial period of ARGX-113 monotherapy is judged clinically acceptable; or newly diagnosed patients or relapsing patients off therapy on a first course of oral prednisone at stable dose for at least 2 weeks and for whom ARGX-113 monotherapy is considered not clinically acceptable; or patients who relapse despite oral prednisone at tapered dose +/- a conventional immunosuppressant (e.g. azathioprine, mycophenolate mofetil).
Identified serum levels of autoantibodies directed against Dsg 3 and/or Dsg-1 antigens at screening, using indirect immunofluorescence or ELISA.
Ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), and comply with the study protocol procedures (including required study visits).
Exclusion Criteria:
Pregnant and lactating women, and those intending to become pregnant during the study or within 90 days after the last dosing. Women of childbearing potential should have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline, prior to administration of IMP.
Male patients who are sexually active that do not intend to use effective methods of contraception during the study or within 90 days after the last dosing.
Confirmed diagnosis of paraneoplastic pemphigus, drug-induced pemphigus or any other non-PV/non-PF autoimmune blistering disease.
History of refractory disease to active third line therapy (e.g. intravenous polyvalent human immunoglobulins [IVIg], rituximab, plasma exchange/ immunoadsorption).
Use of therapies other than oral prednisone and conventional immunosuppressants, that can interfere in the clinical course of the disease (e.g. intravenous [IV] prednisolone bolus, dapsone, sulfasalazine, tetracyclines, nicotinamide, plasmapheresis/ plasma exchange, immunoadsorption and IVIg) within 2 months prior to Baseline visit.
Use of rituximab and other CD20 target biologics within 6 months prior to Baseline visit.
History of anaphylactic reaction, or a known hypersensitivity reaction to one of the components of the IMP.
History of vaccination within the last 4 weeks prior to Baseline visit, or with a planned vaccination during the study, with the exception of seasonal vaccination (e.g. influenza vaccine).
Recent serious infection (i.e., requiring injectable antimicrobial therapy or hospitalization) within the 8 weeks prior to Baseline visit.
Known active or chronic viral infection with hepatitis B virus (HBV); refer to the Centers for Disease Control and Prevention (CDC) guidelines.
Known seropositive or active infection with hepatitis C virus (HCV).
Known history of or known viral infection with human immunodeficiency virus (HIV 1 and 2 antibodies).
Body Mass Index (BMI) at Screening > 35,0 kg/m2.
Clinical evidence of significant active, unstable or uncontrolled concomitant disease (e.g. cardiovascular, pulmonary, hematologic, gastrointestinal, endocrinological and metabolic, hepatic, renal, neurologic, malignancy, infectious diseases, coagulopathies, other autoimmune disease) or condition (lack of peripheral venous access, recent major surgery, etc), which, in the opinion of the investigator, puts the patient at undue risk or may affect the interpretation of the results.
Patients in general health condition not allowing study participation (Karnofsky index < 60%; see Appendix 14.2).
At Screening, have clinically significant laboratory abnormalities as below:
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN)
Total serum bilirubin of > 1.5 x ULN (except for Grade 1 hyperbilirubinemia as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), due solely to a documented medical diagnosis of Gilbert's syndrome)
Serum creatinine of > 1.5 mg/dL or creatinine clearance < 50 mL/min (using the Chronic Kidney Disease Epidemiology Creatinine formula)
Hemoglobin (Hb) ≤ 9 g/dL
International normalized ratio (INR) > 1.5 or activated partial thromboplastin time (aPTT) > 1.5 x ULN
Total immunoglobulin G (IgG) level < 6 g/L
Presence of > 1 + proteinuria dipstick
Patient having participated in another interventional study within the last 3 months prior to Baseline visit.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Dupuy, MD
Organizational Affiliation
argenx
Official's Role
Study Director
Facility Information:
Facility Name
University of Lübeck and UKSH, Department of Dermatology and Lübeck Institute of Experimental Dermatology
City
Lübeck
Country
Germany
Facility Name
Clinic of Dermatology and Allergology - Philipps University Marburg
City
Marburg
Country
Germany
Facility Name
University of Debrecen Medical Center Department of Dermatology
City
Debrecen
Country
Hungary
Facility Name
University of Pécs Clinical Center , Department of Dermatology, Venerology and Oncodermatology
City
Pécs
Country
Hungary
Facility Name
University of Szeged Faculty of Medicine Albert Szent-Györgyi Medical Center Department of Dermatology and Allergology
City
Szeged
Country
Hungary
Facility Name
HaEmek Medical center, Dermatology Department
City
'Afula
Country
Israel
Facility Name
Department of Dermatology, The Chaim Sheba Medical Center
City
Tel Aviv
Country
Israel
Facility Name
Department of dermatology, The Tel Aviv Sourasky Medical Center
City
Tel Aviv
Country
Israel
Facility Name
Dermopathic Institute of the Immaculate - Foundation "Luigi Maria Monti"
City
Rome
Country
Italy
Facility Name
Foundation Policlinico A. Gemelli - Dermatology Department
City
Rome
Country
Italy
Facility Name
National Medical University named after O.O.Bohomolets, Department of Dermatology and Venereology based on Oleksandrivska Clinical Hospital of Kyiv City, Department of Dermatology
City
Kyiv
Country
Ukraine
Facility Name
Municipal Institution "Zaporizhzhya Regional Dermatology and Venereology Clinical Dispensary" of Zaporizhzhya Regional Council
City
Zaporizhzhya
Country
Ukraine
12. IPD Sharing Statement
Citations:
PubMed Identifier
35663943
Citation
Maho-Vaillant M, Sips M, Golinski ML, Vidarsson G, Goebeler M, Stoevesandt J, Bata-Csorgo Z, Balbino B, Verheesen P, Joly P, Hertl M, Calbo S. FcRn Antagonism Leads to a Decrease of Desmoglein-Specific B Cells: Secondary Analysis of a Phase 2 Study of Efgartigimod in Pemphigus Vulgaris and Pemphigus Foliaceus. Front Immunol. 2022 May 18;13:863095. doi: 10.3389/fimmu.2022.863095. eCollection 2022.
Results Reference
derived
PubMed Identifier
34608631
Citation
Goebeler M, Bata-Csorgo Z, De Simone C, Didona B, Remenyik E, Reznichenko N, Stoevesandt J, Ward ES, Parys W, de Haard H, Dupuy P, Verheesen P, Schmidt E, Joly P; ARGX-113-1701 Investigator Study Group. Treatment of pemphigus vulgaris and foliaceus with efgartigimod, a neonatal Fc receptor inhibitor: a phase II multicentre, open-label feasibility trial. Br J Dermatol. 2022 Mar;186(3):429-439. doi: 10.1111/bjd.20782. Epub 2021 Nov 28.
Results Reference
derived
Learn more about this trial
A Study to Evaluate the Safety, PD, PK and Efficacy of ARGX-113 in Patients With Pemphigus
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