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)

argenx12 sites in 5 countries34 target enrollmentOctober 18, 2017

ConditionsPemphigus Vulgaris Pemphigus Foliaceus

InterventionsARGX-113

DrugsARGX-113

Overview

Phase: Phase 2
Intervention: ARGX-113
Conditions: Pemphigus Vulgaris
Sponsor: argenx
Enrollment: 34
Locations: 12
Primary Endpoint: Safety and tolerability as measured by the incidence and severity of treatment-emergent (serious) adverse events over the study.
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

October 18, 2017

End Date

October 28, 2020

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

argenx

Responsible Party

Sponsor

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.

Arms & Interventions

ARGX-113

Intervention: ARGX-113

Outcomes

Primary Outcomes

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 Outcomes

Evaluation of serum levels of total IgG and subtypes (IgG1, IgG2, IgG3, IgG4)(Up to 6 months)
Time to disease control (DC), control being defined as the absence of new lesions and established lesions beginning to heal(Up to 6 months)
Evaluation of serum levels of anti Dsg-1 and -3 autoantibodies(Up to 6 months)
Incidence of anti-drug antibodies (ADA) to ARGX 113(Up to 6 months)
Pemphigus Disease Area Index (PDAI)(Up to 6 months)
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)
Pharmacokinetic parameters of ARGX 113: Tmax(Up to 6 months)
Pharmacokinetic parameters of ARGX 113: Cmax(Up to 6 months)