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

Pemphigus Vulgaris Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03334058
• Other study ID #: ARGX-113-1701
• Secondary ID: 2017-002333-40
• Status: Completed
• Phase: Phase 2
• Start date: October 18, 2017
• Est. completion date: October 28, 2020

Study information

• Verified date: November 2020
• Source: argenx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: October 28, 2020
• Est. primary completion date: October 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pemphigus
• Pemphigus Foliaceus
• Pemphigus Vulgaris

Intervention

Drug:
• ARGX-113
human IgG1-derived Fc fragment that binds to human neonatal Fc receptor (FcRn)

Locations

Country	Name	City	State
Germany	University of Lübeck and UKSH, Department of Dermatology and Lübeck Institute of Experimental Dermatology	Lübeck
Germany	Clinic of Dermatology and Allergology - Philipps University Marburg	Marburg
Hungary	University of Debrecen Medical Center Department of Dermatology	Debrecen
Hungary	University of Pécs Clinical Center , Department of Dermatology, Venerology and Oncodermatology	Pécs
Hungary	University of Szeged Faculty of Medicine Albert Szent-Györgyi Medical Center Department of Dermatology and Allergology	Szeged
Israel	HaEmek Medical center, Dermatology Department	'Afula
Israel	Department of Dermatology, The Chaim Sheba Medical Center	Tel Aviv
Israel	Department of dermatology, The Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Dermopathic Institute of the Immaculate - Foundation "Luigi Maria Monti"	Rome
Italy	Foundation Policlinico A. Gemelli - Dermatology Department	Rome
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	Kyiv
Ukraine	Municipal Institution "Zaporizhzhya Regional Dermatology and Venereology Clinical Dispensary" of Zaporizhzhya Regional Council	Zaporizhzhya

Sponsors (1)

Lead Sponsor	Collaborator
argenx

Countries where clinical trial is conducted

Germany,  Hungary,  Israel,  Italy,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability as measured by the incidence and severity of treatment-emergent (serious) adverse events over the study.		Up to 6 months
Secondary	Evaluation of serum levels of total IgG and subtypes (IgG1, IgG2, IgG3, IgG4)		Up to 6 months
Secondary	Evaluation of serum levels of anti Dsg-1 and -3 autoantibodies		Up to 6 months
Secondary	Pemphigus Disease Area Index (PDAI)	The score has a range from 0 to 263, the higher the score, the more severe the disease.	Up to 6 months
Secondary	Time to disease control (DC), control being defined as the absence of new lesions and established lesions beginning to heal		Up to 6 months
Secondary	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		Up to 6 months
Secondary	Pharmacokinetic parameters of ARGX 113: Tmax		Up to 6 months
Secondary	Pharmacokinetic parameters of ARGX 113: Cmax		Up to 6 months
Secondary	Incidence of anti-drug antibodies (ADA) to ARGX 113		Up to 6 months