Clinical trial NCT04598451: A Study to Assess the Efficacy and Safety of a Subcutaneous Formulation of Efgartigimod PH20 SC in Adults With Pemphigus (Vulgaris or Foliaceus)
Official title: A Randomized, Double-Blinded, Placebo-Controlled Trial to Investigate the Efficacy, Safety, and Tolerability of Efgartigimod PH20 SC in Adult Patients With Pemphigus (Vulgaris or Foliaceus)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pemphigus Vulgaris
Pemphigus Foliaceus
Lead sponsor: argenx
Sponsor class: INDUSTRY
First posted: 2020-10-22
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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 participant is male or female, and aged from 18 years at the time of signing the informed consent form (ICF).
3. 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).
4. The participant meets one of the following profiles:

   1. Newly diagnosed disease with PDAI ≥15 at baseline and naïve to treatment
   2. 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.
   3. 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.
   4. 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.
5. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating clinical trials and:

   1. 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.
   2. 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
6. 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.

Exclusion Criteria:

1. 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.
2. Participants with mild disease severity as defined by PDAI \<15 at baseline.
3. 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).
4. 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.
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 participant has a known contraindication to oral prednisone.
8. The participant has a history of refractory disease, as defined by a failure to respond to first-line and second-line therapies
9. 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
10. 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.
11. Pregnant and lactating women and those intending to become pregnant during the trial.
12. Current or history (i.e. 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 participant has a Karnofsky Performance score \<60%.
15. Vaccination with live viral vaccines within 28 days prior to randomization.
16. The participant 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: Hepatitis B Virus, Hepatitis C Virus , HIV.
18. The participant has total immunoglobulin G (IgG) \<6 g/L at screening.
19. The participant has previously participated in a trial with efgartigimod and has received at least one administration of IMP.
20. Use of an investigational drug within 3 months or 5 half-lives of the drug (whichever is longer) prior to first IMP administration

Primary outcomes:
measure: Number of Pemphigus Vulgaris (PV) Participants Who Achieve Complete Clinical Remission (CR) on Minimal Prednisone Therapy
timeFrame: up to 30 weeks treatment period
Secondary outcomes:
measure: Number of Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF) Participants Who Achieve Complete Clinical Remission (CR) on Minimal Prednisone Therapy Within 30 Weeks
timeFrame: up to 30 weeks treatment period
measure: Normalized Cumulative Prednisone Dose During the Treatment Period in Pemphigus Vulgaris Participants
timeFrame: Up to 30 weeks
measure: Time to Complete Clinical Remission (CR) in Pemphigus Vulgaris Participants
timeFrame: Up to 30 weeks
measure: Time to Disease Control (DC) in Pemphigus Vulgaris (PV) Participants
timeFrame: Up to 30 weeks
measure: Normalized Cumulative Prednisone Dose During the Treatment Period in Pemphigus Vulgaris and Pemphigus Foliaceus Participants
timeFrame: Up to 30 weeks
measure: Time to Complete Clinical Remission (CR) in Pemphigus Vulgaris and Pemphigus Foliaceus Participants
timeFrame: Up to 30 weeks
measure: Time to Disease Control in Pemphigus Vulgaris and Pemphigus Foliaceus Participants
timeFrame: Up to 30 weeks
Other outcomes:
Locations:
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state: Alabama
city: Scottsdale
country: United States
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state: Arizona
city: Redwood City
country: United States
facility: Investigator site 121 - US0010092
state: California
city: Castle Rock
country: United States
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facility: Investigator site 2 - US0010087
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city: Miami
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state: Florida
city: Orlando
country: United States
facility: Investigator site 78 - US0010109
state: Florida
city: West Lafayette
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facility: Investigator site 127 - US0010155
state: Indiana
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country: United States
facility: Investigator site 61 - US0010090
state: Minnesota
city: Saint Louis
country: United States
facility: Investigator site 102 - US0010098
state: Missouri
city: Buffalo
country: United States
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state: New York
city: New York
country: United States
facility: Investigator site 136 - US0010196
state: New York
city: Durham
country: United States
facility: Investigator site 60 - US0010096
state: North Carolina
city: Cleveland
country: United States
facility: Investigator site 20 - US0010094
state: Ohio
city: Philadelphia
country: United States
facility: Investigator site 73 - US00100
state: Pennsylvania
city: Philadelphia
country: United States
facility: Investigator site 101 - US0010097
state: Pennsylvania
city: Dallas
country: United States
facility: Investigator site 98 - US0010107
state: Texas
city: Dripping Springs
country: United States
facility: Investigator site 1 - US0010084
state: Texas
city: Houston
country: United States
facility: Investigator site 126 - US0010182
state: Texas
city: Houston
country: United States
facility: Investigator site 88 - US0010114
state: Texas
city: Norfolk
country: United States
facility: Investigator site 59 - US0010106
state: Virginia
city: Sydney
country: Australia
facility: Investigator site 24 - AU0610006
state: New South Wales
city: Parkville
country: Australia
facility: Investigator site 5 - AU0610007
state: Victoria
city: Melbourne
country: Australia
facility: Investigator site 103 - AU0610013
city: Pleven
country: Bulgaria
facility: Investigator site 30 - BG350012
city: Plovdiv
country: Bulgaria
facility: Investigator site 31 - BG3590013
city: Sofia
country: Bulgaria
facility: Investigator site 4 - BG3590010
city: Sofia
country: Bulgaria
facility: Investigator site 2 - BG3590009
city: Sofia
country: Bulgaria
facility: Investigator site 13 - BG3590011
city: Beijing
country: China
facility: Investigator site 110 - CN0860017
city: Chendu
country: China
facility: Investigator site 111 - CN0860018
city: Chongqing
country: China
facility: Investigator site 131 - CH0860027
city: Fujian
country: China
facility: Investigator site 118 - CN0860023
city: Guangzhou
country: China
facility: Investigator site 120 - CN0860022
city: Guangzhou
country: China
facility: Investigator site 128 - CH0860053
city: Guanzhou
country: China
facility: Investigator site 109 - CN0860021
city: Nanjing
country: China
facility: Investigator site 119 - CN0860024
city: Shanghai
country: China
facility: Investigator site 112 - CN0860020
city: Shanghai
country: China
facility: Investigator site 108 - CN0860016
city: Wuhan
country: China
facility: Investigator site 113 - CN0860025
city: Wuhan
country: China
facility: Investigator site 123 - CN0860019
city: Zhengzhou
country: China
facility: Investigator site 129 - CH0860026
city: Bobigny
country: France
facility: Investigator site 34 - FR0330028
city: La Tronche
country: France
facility: Investigator site 33 - FR0330027
city: Rouen
country: France
facility: Investigator site 46 - FR0330029
city: Saint-Étienne
country: France
facility: Investigator site 32 - FR0330026
city: Tbilisi
country: Georgia
facility: Investigator site 63 - GE9950014
city: Tbilisi
country: Georgia
facility: Investigator site 132 - GE9950030
city: Tbilisi
country: Georgia
facility: Investigator site 35 - GE9950013
city: Tbilisi
country: Georgia
facility: Investigator site 36 - GE9950015
city: Berlin
country: Germany
facility: Investigator site 64 - DE0490029
city: Dresden
country: Germany
facility: Investigator site 48 - DE0490030
city: Frankfurt am main
country: Germany
facility: Investigator site 49 - DE0490024
city: Freiburg
country: Germany
facility: Investigator site 47 - DE0490023
city: Kiel
country: Germany
facility: Investigator site 38 - DE0490028
city: Lübeck
country: Germany
facility: Investigator site 37 - DE0490002
city: Marburg
country: Germany
facility: Investigator site 68 - DE0490001
city: Tübingen
country: Germany
facility: Investigator site 25 - DE0490025
city: Ulm
country: Germany
facility: Investigator site 79 - DE0490027
city: Würzburg
country: Germany
facility: Investigator site 21 - DE0490026
city: Athens
country: Greece
facility: Investigator site 40 - GR0300004
city: Athens
country: Greece
facility: Investigator site 51 - GR0300006
city: Athens
country: Greece
facility: Investigator site 69 - GR0300001
city: Chaïdári
country: Greece
facility: Investigator site 39 - GR0300003
city: Thessaloníki
country: Greece
facility: Investigator site 50 - GR0300002
city: Thessaloníki
country: Greece
facility: Investigator site 41 - GR0300005
city: Budapest
country: Hungary
facility: Investigator site 133 - HU0360023
city: Debrecen
country: Hungary
facility: Investigator site 22 - HU0360003
city: Pécs
country: Hungary
facility: Investigator site 14 - HU0360001
city: Szeged
country: Hungary
facility: Investigator site 42 - HU0360002
city: Ahmedabad
country: India
facility: Investigator site 80 - IN0910002
city: Chandigarh
country: India
facility: Investigator site 100 - IN0910001
city: Lucknow
country: India
facility: Investigator site 90 - IN0910004
city: Nagpur
country: India
facility: Investigator site 91 - IN0910003
city: Tel Aviv
country: Israel
facility: Investigator site 12 - ISR9720002
city: Roma
country: Italy
facility: Investigator site 11 - IT0390006
state: Lazio
city: Catania
country: Italy
facility: Investigator site 104 - IT0390039
city: Firenze
country: Italy
facility: Investigator site 52 - IT0390031
city: Genova
country: Italy
facility: Investigator site 92 - IT0390030
city: Perugia
country: Italy
facility: Investigator site 70 - IT0390038
city: Roma
country: Italy
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city: Siena
country: Italy
facility: Investigator site 71 - IT0390040
city: Aichi
country: Japan
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city: Hiroshima
country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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city: Katowice
country: Poland
facility: Investigator site 26 - PL0480027
city: Poznań
country: Poland
facility: Investigator site 95 - PL0480036
city: Rzeszów
country: Poland
facility: Investigator site 27 - PL0480025
city: Wrocław
country: Poland
facility: Investigator site 28 - PL0480028
city: Łódź
country: Poland
facility: Investigator site 72 - PL0480032
city: Bucharest
country: Romania
facility: Investigator site 106 - RO0400013
city: Cluj-Napoca
country: Romania
facility: Investigator site 105 - RO0400014
city: Iaşi
country: Romania
facility: Investigator site 107 - RO0400015
city: Chelyabinsk
country: Russian Federation
facility: Investigator site 54 - RU0070035
city: Ekaterinburg
country: Russian Federation
facility: Investigator site 58 - RU0070033
city: Kazan
country: Russian Federation
facility: Investigator site 57 - RU0070029
city: Krasnodar
country: Russian Federation
facility: Investigator site 55 - RU0070030
city: Rostov-on-Don
country: Russian Federation
facility: Investigator site 53 - RU0070032
city: Saint Petersburg
country: Russian Federation
facility: Investigator site 56 - RU0070031
city: Saint Petersburg
country: Russian Federation
facility: Investigator site 65 - RU0070034
city: Saratov
country: Russian Federation
facility: Investigator site 66 - RU0070028
city: Belgrade
country: Serbia
facility: Investigator site 122 - RS3810010
city: Belgrad
country: Serbia
facility: Investigator site 116 - RS3810011
city: Niš
country: Serbia
facility: Investigator site 115 - RS3810012
city: Novi Sad
country: Serbia
facility: Investigator site 114 - RS3810009
city: Barcelona
country: Spain
facility: Investigator site 29 - ES0340026
city: Barcelona
country: Spain
facility: Investigator site 15 - ES0340032
city: Granada
country: Spain
facility: Investigator site 130 - ES0340053
city: Madrid
country: Spain
facility: Investigator site 67 - ES0340034
city: Madrid
country: Spain
facility: Investigator site 10 - ES0340025
city: Madrid
country: Spain
facility: Invetistigator site 8 - ES0340029
city: Madrid
country: Spain
facility: Investigator site 6 - ES0340027
city: Málaga
country: Spain
facility: Investigator site 134 - ES0340057
city: Pamplona
country: Spain
facility: Investigator site 23 - ES0340031
city: Sevilla
country: Spain
facility: Investigator site 7 - ES0340028
city: Gaziantep
country: Turkey
facility: Investigator site 76 - TR0900020
city: Istanbul
country: Turkey
facility: Investigator site 75 - TR0900012
city: Istanbul
country: Turkey
facility: Investigator site 87 - TR0900011
city: Dnipro
country: Ukraine
facility: Investigator site 89 - UA3800017
city: Ivano-Frankivs'k
country: Ukraine
facility: Investigator site 45 - UA3800023
city: Kyiv
country: Ukraine
facility: Investigator site 16 - UA3800020
city: Kyiv
country: Ukraine
facility: Investigator site 18 - UA3800019
city: Lviv
country: Ukraine
facility: Investigator site 62 - UA3800021
city: Zaporizhzhia
country: Ukraine
facility: Investigator site 17 - UA3800018
city: Birmingham
country: United Kingdom
facility: Investigator site 117 - UK0440021
city: Bristol
country: United Kingdom
facility: Investigator site 96 - UK0440022
city: Southampton
country: United Kingdom
facility: Investigator site 135 - GB0440037
Study officials:
References: