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A Study to Evaluate the Safety, PD, PK and Efficacy of ARGX-113 in Patients With Pemphigus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03334058
Recruitment Status : Recruiting
First Posted : November 7, 2017
Last Update Posted : August 29, 2019
Sponsor:
Information provided by (Responsible Party):
argenx BVBA

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.


Condition or disease Intervention/treatment Phase
Pemphigus Vulgaris Pemphigus Foliaceus Drug: ARGX-113 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 18, 2017
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pemphigus

Arm Intervention/treatment
Experimental: ARGX-113 Drug: ARGX-113
human IgG1-derived Fc fragment that binds to human neonatal Fc receptor (FcRn)




Primary Outcome Measures :
  1. 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 Measures :
  1. Evaluation of serum levels of total IgG and subtypes (IgG1, IgG2, IgG3, IgG4) [ Time Frame: Up to 6 months ]
  2. Evaluation of serum levels of anti Dsg-1 and -3 autoantibodies [ Time Frame: Up to 6 months ]
  3. Pemphigus Disease Area Index (PDAI) [ Time Frame: Up to 6 months ]
    The score has a range from 0 to 263, the higher the score, the more severe the disease.

  4. 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 ]
  5. 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 ]
  6. Pharmacokinetic parameters of ARGX 113: Tmax [ Time Frame: Up to 6 months ]
  7. Pharmacokinetic parameters of ARGX 113: Cmax [ Time Frame: Up to 6 months ]
  8. Incidence of anti-drug antibodies (ADA) to ARGX 113 [ Time Frame: Up to 6 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients aged ≥ 18 years.
  2. Clinical diagnosis of PV or PF, that has been confirmed by positive direct immunofluorescence and by positive indirect immunofluorescence and/or ELISA.
  3. Mild to moderate disease severity (PDAI < 45).
  4. 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).
  5. Identified serum levels of autoantibodies directed against Dsg 3 and/or Dsg-1 antigens at screening, using indirect immunofluorescence or ELISA.
  6. 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:

  1. 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.
  2. 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.
  3. Confirmed diagnosis of paraneoplastic pemphigus, drug-induced pemphigus or any other non-PV/non-PF autoimmune blistering disease.
  4. History of refractory disease to active third line therapy (e.g. intravenous polyvalent human immunoglobulins [IVIg], rituximab, plasma exchange/ immunoadsorption).
  5. 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.
  6. Use of rituximab and other CD20 target biologics within 6 months prior to Baseline visit.
  7. History of anaphylactic reaction, or a known hypersensitivity reaction to one of the components of the IMP.
  8. 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).
  9. Recent serious infection (i.e., requiring injectable antimicrobial therapy or hospitalization) within the 8 weeks prior to Baseline visit.
  10. Known active or chronic viral infection with hepatitis B virus (HBV); refer to the Centers for Disease Control and Prevention (CDC) guidelines.
  11. Known seropositive or active infection with hepatitis C virus (HCV).
  12. Known history of or known viral infection with human immunodeficiency virus (HIV 1 and 2 antibodies).
  13. Body Mass Index (BMI) at Screening > 35,0 kg/m2.
  14. 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.
  15. Patients in general health condition not allowing study participation (Karnofsky index < 60%; see Appendix 14.2).
  16. At Screening, have clinically significant laboratory abnormalities as below:

    1. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN)
    2. 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)
    3. Serum creatinine of > 1.5 mg/dL or creatinine clearance < 50 mL/min (using the Chronic Kidney Disease Epidemiology Creatinine formula)
    4. Hemoglobin (Hb) ≤ 9 g/dL
    5. International normalized ratio (INR) > 1.5 or activated partial thromboplastin time (aPTT) > 1.5 x ULN
    6. Total immunoglobulin G (IgG) level < 6 g/L
    7. Presence of > 1 + proteinuria dipstick
  17. Patient having participated in another interventional study within the last 3 months prior to Baseline visit.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03334058


Contacts
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Contact: Patrick Dupuy, MD +32(0) 475 781 996 pdupuy@argenx.com

Locations
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Germany
University of Lübeck and UKSH, Department of Dermatology and Lübeck Institute of Experimental Dermatology Recruiting
Lübeck, Germany
Contact: Enno Schmidt, MD         
Clinic of Dermatology and Allergology - Philipps University Marburg Recruiting
Marburg, Germany
Contact: Rüdiger Eming, Prof         
Hungary
University of Debrecen Medical Center Department of Dermatology Recruiting
Debrecen, Hungary
Contact: Eva Remenyik, Prof         
University of Pécs Clinical Center , Department of Dermatology, Venerology and Oncodermatology Recruiting
Pécs, Hungary
Contact: Roland Gyulai, Prof         
University of Szeged Faculty of Medicine Albert Szent-Györgyi Medical Center Department of Dermatology and Allergology Recruiting
Szeged, Hungary
Contact: Zsuzsanna Bata, MD         
Israel
HaEmek Medical center, Dermatology Department Recruiting
'Afula, Israel
Contact: Michael Ziv, MD         
Department of Dermatology, The Chaim Sheba Medical Center Recruiting
Tel Aviv, Israel
Contact: Sharon Baum, MD         
Department of dermatology, The Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv, Israel
Contact: Tali Zeeli, MD         
Italy
Dermopathic Institute of the Immaculate - Foundation "Luigi Maria Monti" Recruiting
Rome, Italy
Contact: Biagio Didona, Dr         
Foundation Policlinico A. Gemelli - Dermatology Department Recruiting
Rome, Italy
Contact: Clara De Simone, Prof         
Ukraine
National Medical University named after O.O.Bohomolets, Department of Dermatology and Venereology based on Oleksandrivska Clinical Hospital of Kyiv City, Department of Dermatology Recruiting
Kyiv, Ukraine
Contact: Viktor Stepanenko, Prof         
Municipal Institution "Zaporizhzhya Regional Dermatology and Venereology Clinical Dispensary" of Zaporizhzhya Regional Council Recruiting
Zaporizhzhya, Ukraine
Contact: Natalya Reznichenko, MD         
Sponsors and Collaborators
argenx BVBA
Investigators
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Study Director: Patrick Dupuy, MD argenx BVBA
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Responsible Party: argenx BVBA
ClinicalTrials.gov Identifier: NCT03334058    
Other Study ID Numbers: ARGX-113-1701
2017-002333-40 ( EudraCT Number )
First Posted: November 7, 2017    Key Record Dates
Last Update Posted: August 29, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pemphigus
Skin Diseases, Vesiculobullous
Skin Diseases
Autoimmune Diseases
Immune System Diseases