A Study to Assess the Efficacy and Safety of a Subcutaneous Formulation of Efgartigimod PH20 SC in Adults With Pemphigus (Vulgaris or Foliaceus)
- Conditions
- Pemphigus VulgarisPemphigus Foliaceus
- Interventions
- Registration Number
- NCT04598451
- Lead Sponsor
- argenx
- Brief Summary
This is a prospective, multicenter, randomized, double-blinded, placebo-controlled trial to investigate the efficacy, safety, patient outcome measures, tolerability, immunogenicity, PK, and PD of efgartigimod PH20 SC in adult participants aged from 18 years with PV or PF. The trial comprises a screening period of up to 3 weeks, a treatment period of up to 30 weeks, and an 8-week follow-up period for participants who do not enroll into the open-label extension (OLE) trial ARGX-113-1905. The primary objective of the ARGX-113-1904 trial is to demonstrate the efficacy of subcutaneous administration of efgartigimod co-formulated with recombinant human hyaluronidase PH20 (Efgartigimod PH20 SC) compared to placebo in the treatment of participants with Pemphigus Vulgaris (PV). Secondary objectives are to also demonstrate the efficacy of efgartigimod PH20 SC in the treatment of participants with Pemphigus Foliaceus (PF), and to demonstrate early onset of action and a prednisone-sparing effect. After confirmation of eligibility, participants will be randomized in a 2: 1 ratio to receive efgartigimod PH20 SC or placebo
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 222
-
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).
-
The participant is male or female, and aged from 18 years at the time of signing the informed consent form (ICF).
-
The participant 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 enzyme-linked immunosorbent assay (ELISA).
-
The participant meets one of the following profiles:
- Newly diagnosed disease with PDAI ≥15 at baseline and naïve to treatment
- Newly diagnosed disease with PDAI ≥15 while receiving a first course of oral prednisone (or equivalent). According to clinical judgment, the participant 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.
- Experiencing flare with PDAI ≥15, a maximum of 4 years since diagnosis, and off prednisone therapy ± a conventional immunosuppressant (e.g., azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) or dapsone. Note: conventional immunosuppressants and dapsone must be discontinued before baseline.
- Experiencing flare with PDAI ≥15, a maximum of 4 years since diagnosis, and receiving a tapered dose of oral prednisone (or the equivalent), provided that prednisone has been given at stable dose ± a conventional immunosuppressant for at least 2 weeks and patients are fit to start prednisone treatment at 0.5 mg/kg qd at baseline.
-
Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating clinical trials and:
-
Male participants: Male participants must agree to use acceptable method of contraception, and not donate sperm from signing the ICF until the end of the study.
-
Female participants: Women of childbearing potential must:
- have a negative serum pregnancy test at screening and negative urine pregnancy test at baseline before the IMP can be administered.
- agree to use a highly effective or acceptable contraception method, which should be maintained at minimum until after the last dose of IMP
-
-
For Japanese participants enrolled in sites in Japan only: A Japanese participant is defined as a participant whose parents and 4 grandparents are Japanese, and who has Japanese nationality, was born in Japan, has not lived outside of Japan for a total of >10 years, and currently lives in Japan.
-
Participant has a confirmed diagnosis of paraneoplastic pemphigus, drug-induced pemphigus, pemphigus vegetans, pemphigus erythematosus, or any other non-PV/non-PF autoimmune blistering disease.
-
Participants with mild disease severity as defined by PDAI <15 at baseline.
-
Participants 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).
-
The participant has been administered therapy(ies) other than oral prednisone or conventional immunosuppressants (e.g., azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) or dapsone 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 at doses above the recommended daily allowance (RDA)/dietary reference intake (DRI), plasmapheresis/ plasma exchange, immunoadsorption, and IVIg.
-
Use of any monoclonal antibody (including rituximab or another anti-CD20 biologic) within 6 months before the baseline visit.
-
Known hypersensitivity to any of the components of the administered treatments.
-
The participant has a known contraindication to oral prednisone.
-
The participant has a history of refractory disease, as defined by a failure to respond to first-line and second-line therapies
-
Participants who have a history of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before first IMP administration. Participants with any of the following cancers can be included at any time, provided they are adequately treated prior to their participation in the study:
- Basal cell or squamous cell skin cancer,
- Carcinoma in situ of the cervix,
- Carcinoma in situ of the breast,
- Incidental histological finding of prostate cancer
-
Participants with clinical evidence of other significant serious disease or participants 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.
-
Pregnant and lactating women and those intending to become pregnant during the trial.
-
Current or history (i.e. within 12 months of screening) of alcohol, drug, or medication abuse.
-
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.
-
The participant has a Karnofsky Performance score <60%.
-
Vaccination with live viral vaccines within 28 days prior to randomization.
-
The participant has clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection.
-
Positive serum test at screening for an active viral infection with any of the following conditions: Hepatitis B Virus, Hepatitis C Virus , HIV.
-
The participant has total immunoglobulin G (IgG) <6 g/L at screening.
-
The participant has previously participated in a trial with efgartigimod and has received at least one administration of IMP.
-
Use of an investigational drug within 3 months or 5 half-lives of the drug (whichever is longer) prior to first IMP administration
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description efgartigimod PH20 SC efgartigimod PH20 SC patients receiving efgartigimod PH20 SC on top of prednisone placebo Placebo patients receiving placebo on top of prednisone efgartigimod PH20 SC prednisone patients receiving efgartigimod PH20 SC on top of prednisone placebo prednisone patients receiving placebo on top of prednisone
- Primary Outcome Measures
Name Time Method Number of Pemphigus Vulgaris (PV) Participants Who Achieve Complete Clinical Remission (CR) on Minimal Prednisone Therapy up to 30 weeks treatment period Proportion of participants with pemphigus vulgaris who had CRmin within 30 weeks, defined as the absence of new lesions and complete healing of established lesions while the participant was receiving prednisone at ≤10 mg/day for at least 8 weeks.
- Secondary Outcome Measures
Name Time Method Number of Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF) Participants Who Achieve Complete Clinical Remission (CR) on Minimal Prednisone Therapy Within 30 Weeks up to 30 weeks treatment period Proportion of participants with pemphigus vulgaris and pemphigus foliaceus who had CRmin within 30 weeks, defined as the absence of new lesions and complete healing of established lesions while the participant was receiving prednisone at ≤10 mg/day for at least 8 weeks.
Normalized Cumulative Prednisone Dose During the Treatment Period in Pemphigus Vulgaris Participants Up to 30 weeks Normalized Cumulative prednisone dose (NCPD, mg/kg/day) is the average daily intake of all weight-adjusted prednisone doses received during the study, taking into account the number of days in study
Time to Complete Clinical Remission (CR) in Pemphigus Vulgaris Participants Up to 30 weeks Time to complete remission (absence of new lesions and complete healing of established lesions) in participants with pemphigus vulgaris
Time to Disease Control (DC) in Pemphigus Vulgaris (PV) Participants Up to 30 weeks Time to disease control in participants with pemphigus vulgaris (Absence of new lesions and the start of healing of established lesions)
Normalized Cumulative Prednisone Dose During the Treatment Period in Pemphigus Vulgaris and Pemphigus Foliaceus Participants Up to 30 weeks Normalized Cumulative prednisone dose (NCPD, mg/kg/day) is the average daily intake of all weight-adjusted prednisone doses received during the study, taking into account the number of days in study
Time to Complete Clinical Remission (CR) in Pemphigus Vulgaris and Pemphigus Foliaceus Participants Up to 30 weeks Time to complete remission (absence of new lesions and complete healing of established lesions) in participants with pemphigus vulgaris and pemphigus foliaceus
Time to Disease Control in Pemphigus Vulgaris and Pemphigus Foliaceus Participants Up to 30 weeks Time to disease control in participants with pemphigus vulgaris and pemphigus foliaceus (Absence of new lesions and the start of healing of established lesions)
Trial Locations
- Locations (134)
Investigator site 117 - UK0440021
🇬🇧Birmingham, United Kingdom
Investigator site 30 - BG350012
🇧🇬Pleven, Bulgaria
Investigator site 31 - BG3590013
🇧🇬Plovdiv, Bulgaria
Investigator site 4 - BG3590010
🇧🇬Sofia, Bulgaria
Investigator site 13 - BG3590011
🇧🇬Sofia, Bulgaria
Investigator site 100 - IN0910001
🇮🇳Chandigarh, India
Investigator site 94 - JP0810046
🇯🇵Aichi, Japan
Investigator site 81 - JP0810040
🇯🇵Hiroshima, Japan
Investigator site 84 - JP0810047
🇯🇵Okayama, Japan
Investigator site 91 - IN0910003
🇮🇳Nagpur, India
Investigator site 124 - JP0810067
🇯🇵Sendai, Japan
Investigator site 27 - PL0480025
🇵🇱Rzeszów, Poland
Investigator site 28 - PL0480028
🇵🇱Wrocław, Poland
Investigator site 72 - PL0480032
🇵🇱Łódź, Poland
Investigator site 85 - JP0810050
🇯🇵Kurume, Japan
Investigator site 95 - PL0480036
🇵🇱Poznań, Poland
Investigator site 93 - JP0810041
🇯🇵Okayama, Japan
Investigator site 74 - JP0810045
🇯🇵Sapporo, Japan
Investigator site 121 - US0010092
🇺🇸Redwood City, California, United States
Investigator site 20 - US0010094
🇺🇸Cleveland, Ohio, United States
Investigator site 98 - US0010107
🇺🇸Dallas, Texas, United States
Investigator site 111 - CN0860018
🇨🇳Chendu, China
Investigator site 110 - CN0860017
🇨🇳Beijing, China
Investigator site 120 - CN0860022
🇨🇳Guangzhou, China
Investigator site 76 - TR0900020
🇹🇷Gaziantep, Turkey
Investigator site 125 - US0010153
🇺🇸Castle Rock, Colorado, United States
Investigator site 2 - US0010087
🇺🇸Boca Raton, Florida, United States
Investigator site 78 - US0010109
🇺🇸Orlando, Florida, United States
Investigator site 99 - US0010117
🇺🇸Miami, Florida, United States
Investigator site 127 - US0010155
🇺🇸West Lafayette, Indiana, United States
Investigator site 61 - US0010090
🇺🇸Minneapolis, Minnesota, United States
Investigator site 73 - US00100
🇺🇸Philadelphia, Pennsylvania, United States
Investigator site 136 - US0010196
🇺🇸New York, New York, United States
Investigator site 1 - US0010084
🇺🇸Dripping Springs, Texas, United States
Investigator site 19 - US0010088
🇺🇸Buffalo, New York, United States
Investigator site 24 - AU0610006
🇦🇺Sydney, New South Wales, Australia
Investigator site 60 - US0010096
🇺🇸Durham, North Carolina, United States
Investigator site 103 - AU0610013
🇦🇺Melbourne, Australia
Investigator site 5 - AU0610007
🇦🇺Parkville, Victoria, Australia
Investigator site 101 - US0010097
🇺🇸Philadelphia, Pennsylvania, United States
Investigator site 126 - US0010182
🇺🇸Houston, Texas, United States
Investigator site 88 - US0010114
🇺🇸Houston, Texas, United States
Investigator site 2 - BG3590009
🇧🇬Sofia, Bulgaria
Investigator site 118 - CN0860023
🇨🇳Fujian, China
Investigator site 131 - CH0860027
🇨🇳Chongqing, China
Investigator site 113 - CN0860025
🇨🇳Wuhan, China
Investigator site 12 - ISR9720002
🇮🇱Tel Aviv, Israel
Investigator site 109 - CN0860021
🇨🇳Guanzhou, China
Investigator site 42 - HU0360002
🇭🇺Szeged, Hungary
Investigator site 108 - CN0860016
🇨🇳Shanghai, China
Investigator site 104 - IT0390039
🇮🇹Catania, Italy
Investigator site 119 - CN0860024
🇨🇳Nanjing, China
Investigator site 112 - CN0860020
🇨🇳Shanghai, China
Investigator site 129 - CH0860026
🇨🇳Zhengzhou, China
Investigator site 32 - FR0330026
🇫🇷Saint-Étienne, France
Investigator site 36 - GE9950015
🇬🇪Tbilisi, Georgia
Investigator site 40 - GR0300004
🇬🇷Athens, Greece
Investigator site 37 - DE0490002
🇩🇪Lübeck, Germany
Investigator site 25 - DE0490025
🇩🇪Tübingen, Germany
Investigator site 41 - GR0300005
🇬🇷Thessaloníki, Greece
Investigator site 22 - HU0360003
🇭🇺Debrecen, Hungary
Investigator site 21 - DE0490026
🇩🇪Würzburg, Germany
Investigator site 38 - DE0490028
🇩🇪Kiel, Germany
Investigator site 50 - GR0300002
🇬🇷Thessaloníki, Greece
Investigator site 52 - IT0390031
🇮🇹Firenze, Italy
Investigator site 80 - IN0910002
🇮🇳Ahmedabad, India
Investigator site 92 - IT0390030
🇮🇹Genova, Italy
Investigator site 70 - IT0390038
🇮🇹Perugia, Italy
Investigator site 105 - RO0400014
🇷🇴Cluj-Napoca, Romania
Investigator site 115 - RS3810012
🇷🇸Niš, Serbia
Investigator site 116 - RS3810011
🇷🇸Belgrad, Serbia
Investigator site 15 - ES0340032
🇪🇸Barcelona, Spain
Investigator site 67 - ES0340034
🇪🇸Madrid, Spain
Investigator site 29 - ES0340026
🇪🇸Barcelona, Spain
Investigator site 130 - ES0340053
🇪🇸Granada, Spain
Investigator site 134 - ES0340057
🇪🇸Málaga, Spain
Investigator site 89 - UA3800017
🇺🇦Dnipro, Ukraine
Investigator site 16 - UA3800020
🇺🇦Kyiv, Ukraine
Investigator site 87 - TR0900011
🇹🇷Istanbul, Turkey
Investigator site 7 - ES0340028
🇪🇸Sevilla, Spain
Investigator site 17 - UA3800018
🇺🇦Zaporizhzhia, Ukraine
Investigator site 96 - UK0440022
🇬🇧Bristol, United Kingdom
Investigator site 102 - US0010098
🇺🇸Saint Louis, Missouri, United States
Investigator site 59 - US0010106
🇺🇸Norfolk, Virginia, United States
Investigator site 77 - US0010086
🇺🇸Birmingham, Alabama, United States
Investigator site 128 - CH0860053
🇨🇳Guangzhou, China
Investigator site 123 - CN0860019
🇨🇳Wuhan, China
Investigator site 33 - FR0330027
🇫🇷La Tronche, France
Investigator site 46 - FR0330029
🇫🇷Rouen, France
Investigator site 34 - FR0330028
🇫🇷Bobigny, France
Investigator site 63 - GE9950014
🇬🇪Tbilisi, Georgia
Investigator site 132 - GE9950030
🇬🇪Tbilisi, Georgia
Investigator site 64 - DE0490029
🇩🇪Berlin, Germany
Investigator site 35 - GE9950013
🇬🇪Tbilisi, Georgia
Investigator site 49 - DE0490024
🇩🇪Frankfurt am main, Germany
Investigator site 68 - DE0490001
🇩🇪Marburg, Germany
Investigator site 48 - DE0490030
🇩🇪Dresden, Germany
Investigator site 47 - DE0490023
🇩🇪Freiburg, Germany
Investigator site 51 - GR0300006
🇬🇷Athens, Greece
Investigator site 79 - DE0490027
🇩🇪Ulm, Germany
Investigator site 69 - GR0300001
🇬🇷Athens, Greece
Investigator site 39 - GR0300003
🇬🇷Chaïdári, Greece
Investigator site 133 - HU0360023
🇭🇺Budapest, Hungary
Investigator site 14 - HU0360001
🇭🇺Pécs, Hungary
Investigator site 90 - IN0910004
🇮🇳Lucknow, India
Investigator site 11 - IT0390006
🇮🇹Roma, Lazio, Italy
Investigator site 43 - IT390005
🇮🇹Roma, Italy
Investigator site 71 - IT0390040
🇮🇹Siena, Italy
Investigator site 83 - JP0810043
🇯🇵Tokyo, Japan
Investigator site 82 - JP0810042
🇯🇵Kōfu, Japan
Investigator site 86 - JP0810049
🇯🇵Osaka, Japan
Investigator site 26 - PL0480027
🇵🇱Katowice, Poland
Investigator site 106 - RO0400013
🇷🇴Bucharest, Romania
Investigator site 107 - RO0400015
🇷🇴Iaşi, Romania
Investigator site 58 - RU0070033
🇷🇺Ekaterinburg, Russian Federation
Investigator site 57 - RU0070029
🇷🇺Kazan, Russian Federation
Investigator site 55 - RU0070030
🇷🇺Krasnodar, Russian Federation
Investigator site 66 - RU0070028
🇷🇺Saratov, Russian Federation
Investigator site 122 - RS3810010
🇷🇸Belgrade, Serbia
Investigator site 6 - ES0340027
🇪🇸Madrid, Spain
Investigator site 62 - UA3800021
🇺🇦Lviv, Ukraine
Investigator site 10 - ES0340025
🇪🇸Madrid, Spain
Invetistigator site 8 - ES0340029
🇪🇸Madrid, Spain
Investigator site 18 - UA3800019
🇺🇦Kyiv, Ukraine
Investigator site 75 - TR0900012
🇹🇷Istanbul, Turkey
Investigator site 23 - ES0340031
🇪🇸Pamplona, Spain
Investigator site 45 - UA3800023
🇺🇦Ivano-Frankivs'k, Ukraine
Investigator site 135 - GB0440037
🇬🇧Southampton, United Kingdom
Investigator site 97 - US0010091
🇺🇸Scottsdale, Arizona, United States
Investigator site 54 - RU0070035
🇷🇺Chelyabinsk, Russian Federation
Investigator site 53 - RU0070032
🇷🇺Rostov-on-Don, Russian Federation
Investigator site 56 - RU0070031
🇷🇺Saint Petersburg, Russian Federation
Investigator site 65 - RU0070034
🇷🇺Saint Petersburg, Russian Federation
Investigator site 114 - RS3810009
🇷🇸Novi Sad, Serbia