E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pemphigus (Vulgaris or Foliaceus) |
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E.1.1.1 | Medical condition in easily understood language |
Pemphigus (Vulgaris or Foliaceus) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052802 |
E.1.2 | Term | Pemphigus vulgaris |
E.1.2 | System Organ Class | 100000004858 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057069 |
E.1.2 | Term | Pemphigus foliaceus |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of ARGX-113 in PV and PF patients |
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E.2.2 | Secondary objectives of the trial |
- 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients aged ≥ 18 years. 2. Clinical diagnosis of mucocutaneous 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 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 pathogenic 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). |
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E.4 | Principal 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 interventional study within the last 3 months prior to Baseline visit. |
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | 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 |
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E.5.2 | 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. -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 Baseline, Visit 3, then at Visits 5, all Maintenance treatment visits, FU-1, FU-2 and FU-3. |
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E.5.2.1 | 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 - at Baseline then at each visit - at Baseline, Visit 3, then at Visits 5, all Maintenance treatment visits, FU-1, FU-2 and FU-3. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Germany |
Hungary |
Israel |
Italy |
Romania |
Ukraine |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |