A study to evaluate the safety and efficacy of ARGX-113 in patients with Mild to Moderate Pemphigus (Vulgaris or Foliaceus)

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2017-002333-40-IT
• Date of registration: 29/01/2021
• Prospective Registration: No
• Primary sponsor: ARGEN-X BVBA
• Public title: A study to evaluate the safety and efficacy of ARGX-113 in patients with Mild to Moderate Pemphigus (Vulgaris or Foliaceus)
• Scientific 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 or Foliaceus) - A study to evaluate the safety and efficacy of ARGX-113 in patients with Mild to Moderate Pemphigus
• Date of first enrolment: 05/01/2018
• Target sample size: 22
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002333-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Hungary, Israel, Italy, Romania, Ukraine

Contacts

• Name: Regulatory
• Affiliation: argenx BVBA

• Name: Regulatory
• Affiliation: argenx BVBA

Key inclusion & exclusion 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 positive indirect immunofluorescence and/or enzyme-linked immunosorbent assay (ELISA
3. Mild to moderate disease severity (Pemphigus Disease Area Index [PDAI] < 45).
4.Newly diagnosed patients or relapsing patients off therapy; 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 antigen 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).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

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 pemphigus foliaceus, 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 known infection with 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:
a. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN)
b. 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)
c. Serum creatinine of > 1.5 mg/dL or creatinine clearance < 50 mL/min (using the Chronic Kidney Disease Epidemiology -Creatinine formula)
d. Hemoglobin (Hb) = 9 g/dL
e. International normalized ratio (INR) > 1.5 or activated partial thromboplastin time (aPTT) > 1.5 x ULN
f. Total immunoglobulin G (IgG) level < 6 g/L
g. Presence of > 1 + proteinuria dipstick
17. Patient having participated in another in

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pemphigus (Vulgaris or Foliaceus)
MedDRA version: 20.0 Level: LLT Classification code 10052802 Term: Pemphigus vulgaris System Organ Class: 100000004858
MedDRA version: 20.0 Level: LLT Classification code 10057069 Term: Pemphigus foliaceus System Organ Class: 100000004858

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Product Name: ARGX-113
Product Code: [ARGX-113]
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: efgartigimod
CAS Number: 1821402-21-4
Current Sponsor code: ARGX-113
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Primary end point(s): - Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) over the study.
- Vital signs, electrocardiogram (ECG) parameters, physical examination abnormalities and clinical laboratory assessments.

Secondary Objective: - To define the therapeutic dose and the dose regimen through the pharmacodynamic (PD) and clinical efficacy findings;
- To evaluate the serum levels of immunoglobulin (Ig) G (total IgG and subtypes) following ARGX-113 treatment;
- To evaluate the serum levels of anti-desmoglein (Dsg)-1 and -3 autoantibodies following ARGX-113 treatment;
- To assess the efficacy on cutaneous and mucosal pemphigus lesions;
- To measure the pharmacokinetics (PK) of ARGX-113;
- To investigate the immunogenicity of ARGX-113.

Timepoint(s) of evaluation of this end point: -Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) will be monitored continuously from signing of informed consent until the last study-related activity
- Vital signs, physical examination abnormalities and clinical laboratory assessments: screening, V1-9
- ECG: screening, v5, v7-9

Main Objective: To evaluate the safety and tolerability of ARGX-113 in PV and PF patients.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - at Baseline then at each visit
- at Baseline then at each visit
- at each visit
- from Visit 2 until control is achieved
- from any visit following DC
-time to end of consolidation
-time to complete clinical remission,, defined as the time at which no new lesions have developed for a minimum of 2 weeks
-time to complete clinical remission , as defined by the absence of new lesions and established lesions completely healed
-time to complete clinical remission under minimal therapy, as defined as a prednisone dose of 10 mg/day or less for at least 8 weeks
- at Baseline then at each visit
- at each visit as per schedule of assessments

Secondary end point(s): -Total IgG and subtypes, at Baseline then at each visit.
-Serum levels of anti-Dsg-1 and -3 autoantibodies, at Baseline then at each visit.
-PDAI, at each visit.
-Time to disease control (DC), control being defined as the absence of new lesions and established lesions beginning to heal, evaluated from Visit 2 until control is achieved.
-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, evaluated from any visit following DC.
- In additional cohort 4 and optional cohort 5, time to end of consolidation, defined as the time at which no new lesions have developed for a minimum of 2 weeks, and approximately 80% of lesions have healed.
- In additional cohort 4 and optional cohort 5, time to complete clinical remission, as defined by the absence of new lesions and established lesions completely healed (except post-inflammatory hyperpigmentation or erythema from resolving lesions).
-In additional cohort 4 and optional cohort 5, time to complete clinical remission under minimal therapy, as defined as a prednisone dose of 10 mg/day or less for at least 8 weeks.
-Pharmacokinetic parameters of ARGX-113, at Baseline then at each visit (pre- and post-dose when IMP is administered).
-Incidence of anti-drug antibodies (ADA) to ARGX-113, at each visit as per schedule of assessments.

Secondary ID(s)

2017-002333-40-DE

ARGX-113-1701

Source(s) of Monetary Support

argenx BVBA

Ethics review

Status: Approved
Approval date: 19/09/2017
Contact: