Health Condition 1: L102- Pemphigus foliaceous Health Condition 2: L100- Pemphigus vulgaris
Conditions
Interventions
Intervention1: ARGX-113 (Efgartigimod PH20 SC): Route of administration: efgartigimod with rHuPH20 will be administered Subcutaneously each week
Duration of therapy: 30 weeks of treatment period.
Do
Sponsors
argenx BV
Eligibility
Inclusion criteria
Inclusion criteria: 1. Ability to understand the requirements of the trial, to provide written informed consent (including consent for the use and disclosure of research-related health information), willingness and ability to comply with the trial protocol procedures (including required trial visits). 2. The patient is male or female, and aged 18 years to 80 years at the time of signing the informed consent form (ICF). 3. The patient has a clinical diagnosis of PV (mucosal, cutaneous, mucocutaneous) or PF which has been confirmed by cutaneous histology, positive direct immunofluorescence (IF), and positive indirect IF and/or ELISA. 4. The patient meets 1 of the following profiles: a. Newly diagnosed disease with PDAI activity score =15 (see Section 10.8) at baseline and naïve to treatment. b. Newly diagnosed disease with PDAI activity score =15 while receiving a first course of oral prednisone (or equivalent). According to clinical judgment, the patient has shown no significant improvement of PV or PF signs for at least 2 weeks before baseline and is considered fit to start prednisone treatment at 0.5 mg/kg qd at baseline. c. Experiencing flare with PDAI activity score =15, a maximum of 4 years since diagnosis, and off prednisone therapy ± a conventional immunosuppressant (eg, azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil). Note: conventional immunosuppressants must be discontinued before baseline. d. Experiencing flare with PDAI activity score =15, a maximum of 4 years since diagnosis, and receiving a tapered dose of oral prednisone (or equivalent), provided that prednisone has been given at stable dose ± a conventional immunosuppressant (eg, azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) for at least 2 weeks and patients are fit to start prednisone treatment at 0.5 mg/kg qd at baseline. Note: conventional immunosuppressants must be discontinued before baseline. 5. Women of childbearing potential (see definition in Section 10.5): a. Must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before trial medication can be administered. b. Must be on a stable regimen for at least 1 month of at least 1 highly effective method of contraception (ie, failure rate of less than 1% per year; see Highly effective methods of female contraception in Section 10.5) during the trial and for 90 days after the last administration of IMP. 6. Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use effective contraception from first administration of IMP through 90 days after the last administration of the IMP. Male patients practicing true sexual abstinence (as consistent with preferred and usual life style) can be included. Sterilized male patients who have had a vasectomy and with documented absence of sperm post-procedure can be included. Male patients are not allowed to donate sperm from first administration of IMP through 90 days after the last dose of IMP.
Exclusion criteria
Exclusion criteria: Exclusion Criteria: Participants are excluded from the trial if any of the following criteria apply: 1. Patient has a confirmed diagnosis of paraneoplastic pemphigus, drug-induced pemphigus, pemphigus vegetans, pemphigus erythematosus, or any other non-PV/non-PF autoimmune blistering disease. 2. Patients with mild disease severity as defined by PDAI activity score 3. Patients who show a significant improvement of PV or PF in the period from screening to baseline according to clinical judgment (eg, the patient has achieved DC or a substantial reduction in PDAI activity score during screening period). 4. The patient has been administered therapy(ies) other than oral prednisone or conventional immunosuppressants (eg, azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) within 2 months before the baseline visit and that can affect clinical disease activity. For example, excluded medications are intravenous methylprednisolone, dapsone, sulfasalazine, tetracyclines, nicotinamide, plasmapheresis/ plasma exchange, immunoadsorption, and IVIg. Note: conventional immunosuppressants must be discontinued before baseline. 5. Use of any monoclonal antibody (including rituximab or another anti-CD20 biologic) within 6 months before the baseline visit. 6. Known hypersensitivity to any of the components of the administered treatments. 7. The patient has a known contraindication to oral prednisone. 8. The patient has a history of refractory disease, as defined by a failure to respond to firstline and second-line therapies. 9. Patients who have a history of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for =3 years before first IMP administration. Patients with any of the following cancers can be included at any time: a. Adequately treated basal cell or squamous cell skin cancer b. Carcinoma in situ of the cervix c. Carcinoma in situ of the breast d. Incidental histological finding of prostate cancer (TNM stage T1a or T1b) 10. Patients with clinical evidence of other significant serious disease or patients who recently underwent or have planned a major surgery during the period of the trial, or any other condition in the opinion of the investigator, that could confound the results of the trial or put the patient at undue risk. 11. Pregnant and lactating women and those intending to become pregnant during the trial or within 90 days after the last administration of IMP. 12. Current or history (ie, within 12 months of screening) of alcohol, drug, or medication abuse. 13. Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of PV or PF or put the participant at undue risk. 14. The patient has a Karnofsky performance score 15. Vaccination with live/attenuated viral vaccines within 28 days prior to randomization (see Section 8.3.7). 16. The patient has clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection. 17. Positive serum test at screening for an active viral infection with any of the following conditions: a. Hepatitis B Virus (HBV) that is indicative of an acute or chronic infection (https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf; see Sect
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate the efficacy of efgartigimod PH20 SC compared to placebo in the treatment of patients with PVTimepoint: Proportion of PV patients who achieve CR on minimal therapy within 30 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the safety of efgartigimod PH20 SC in patients with PV or PF Timepoint: 1_Incidence and severity of TEAEs, adverse events of special interest (AESIs), and serious adverse events (SAEs) by System Organ Class (SOC) and PT 2_Vital signs, physical examination, electrocardiogram (ECG), and clinical laboratory safety evaluations;To demonstrate the efficacy of efgartigimod PH20 SC in the treatment of patients with PV or PFTimepoint: 1_Proportion of PV and PF patients who achieve CR on minimal therapy within 30 weeks 2_Cumulative prednisone dose over the trial in PV patients 3_Time to CR in PV patients 4_Time to DC in PV patients 5_Time to DC in PV and PF patients s 6_Time to complete CR in PV and PF patients 7_Cumulative prednisone dose over the trial in PV and PF patients 8_Rate of treatment failure 9_Rate of flare 10_PDAI at each visit - up to 41weeks;To evaluate the effects of efgartigimod PH20 SC on quality of life (QoL) in patients with PV or PFTimepoint: 1_EuroQol 5-Dimension 5-Level (EQ-5D-5L) score 2_ABQOL score;To evaluate the immunogenicity of efgartigimod PH20 SC in patients with PV or PFTimepoint: Anti-drug antibodies (ADA) to efgartigimod (serum plasma) and rHuPH20 (plasma levels);To evaluate the PD of efgartigimod PH20 SC in patients with PV or PFTimepoint: 1_Total IgG and subtype (IgG1, IgG2, IgG3, IgG4) serum levels 2_Anti-Dsg-1 and -3 autoantibodies serum levels;To evaluate the PK of efgartigimod PH20 SC in patients with PV or PF Timepoint: Efgartigimod serum concentrations | — |
Countries
Australia, Bulgaria, France, Georgia, Germany, Greece, Hungary, India, Israel, Italy, Japan, Poland, Romania, Russian Federation, Spain, Turkey, Ukraine, United Kingdom, United States of America
Contacts
Public ContactRashmi Chitgupi
PPD Pharmaceutical Development India Private Limited
Outcome results
None listed