A Study to Assess the Long-term Safety and Efficacy of a Subcutaneous Formulation of Efgartigimod PH20 SC in Adults With Pemphigus (Vulgaris or Foliaceus) (ADDRESS+)

An Open-Label, Multicenter, Follow-up Trial of ARGX-113-1904 to Evaluate the Safety, Tolerability, and Efficacy of Efgartigimod PH20 SC in Patients With Pemphigus

This is a prospective, multicenter, open label extension (OLE) trial on the efficacy, safety, patient outcome measures, tolerability, immunogenicity, PK and PD of efgartigimod PH20 SC in adult PV or PF participants, who participated in antecedent trial ARGX-113-1904. This trial provides extension of efgartigimod PH20 SC treatment and retreatment options for participants who have been randomized to efgartigimod PH20 SC treatment arm in the trial ARGX-113-1904, and the first treatment of efgartigimod PH20 SC and retreatment options for participants who had been randomized to placebo arm in trial ARGX-113-1904. Trial ARGX-113-1905 evaluates ability to (further) taper prednisone therapy and achieve Clinical Remission (CR) off therapy (CRoff), the ability to achieve CR and CR on minimal therapy (CRmin) for participants who had not yet achieved CRmin, and the ability to treat flare; and assess patient outcome measures and the safety, PD, PK and immunogenicity of efgartigimod PH20 SC over the duration of trial.

Study duration: Up to 60 weeks for participants who receive IMP administration up to 52 weeks and with a follow-up period of 8 weeks after the last IMP administration

Study Overview

• Status: Active, not recruiting
• Conditions: Pemphigus Vulgaris; Pemphigus Foliaceus
• Intervention / Treatment: Biological: efgartigimod PH20 SC; Drug: prednisone

• Study Type: Interventional
• Enrollment (Actual): 183
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sabine Coppieters, MD; Phone Number: +1 857-350-4834; Email: clinicaltrials@argenx.com

Study Locations

• Australia
  • Melbourne, Australia, 3065
    • Investigator site 92 - AU0610013
  • New South Wales
    • Sydney, New South Wales, Australia, 2217
      • Investigator site 15 - AU0610006
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Investigator site 11 - AU0610007
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Investigator site 17 - BG3590012
  • Plovdiv, Bulgaria, 4000
    • Investigator site 18 - BG3590013
  • Sofia, Bulgaria, 1431
    • Investigator site 2 - BG3590010
  • Sofia, Bulgaria, 1510
    • Investigator site 16 - BG3590009
  • Sofia, Bulgaria, 1606
    • Investigator site 3 - BG3590011
• China
  • Beijing, China, 100034
    • Investigator site 101 - CN0860017
  • Chengdu, China, 610000
    • Investigator site 107 - CN0860018
  • Chongqing, China, 400042
    • Investigator site 118 - CH0860027
  • Fuzhou, China, 35005
    • Investigator site 120 - CH0860023
  • Guangzhou, China, 510000
    • Investigator site 119 - CH0860022
  • Guangzhou, China, 51000
    • Investigator site 116 - CH0860053
  • Guanzhou, China, 510000
    • Investigator site 100 - CN0860021
  • Nanjing, China, 210042
    • Investigator site 113 - CN0860024
  • Shanghai, China, 200025
    • Investigator site 102 - CN0860020
  • Shanghai, China, 200040
    • Investigator site 99 - CN0860016
  • Wuhan, China, 430022
    • Investigator site 112 - CN0860019
  • Wuhan, China, 430022
    • Investigator site 121 - CH0860025
  • Zhengzhou, China, 450008
    • Investigator site 117 - CH0860026
• France
  • Bobigny, France, 93000
    • Investigator site 77 - FR0330028
  • La Tronche, France, 38700
    • Investigator site 60 - FR0330027
  • Rouen, France, 76031
    • Investigator site 108 - FR0330029
  • Saint-Étienne, France, 42055
    • Investigator site 51 - FR0330026
• Georgia
  • Tbilisi, Georgia, 0159
    • Investigator site 78 - GE9950014
  • Tbilisi, Georgia, 0160
    • Investigator site 127 - GE9950030
  • Tbilisi, Georgia, 0162
    • Investigator site 32 - GE9950013
  • Tbilisi, Georgia, 0179
    • Investigator site 31 - GE9950015
• Germany
  • Berlin, Germany, 10117
    • Investigator site 45 - DE0490029
  • Dresden, Germany, 01307
    • Investigator site 34 - DE0490030
  • Frankfurt am main, Germany, 60590
    • Investigator site 33 - DE0490024
  • Freiburg, Germany, 79104
    • Investigator site 53 - DE0490023
  • Kiel, Germany, 24105
    • Investigator site 35 - DE0490028
  • Lübeck, Germany, 23538
    • Investigator site 20 - DE0490002
  • Marburg, Germany, 35043
    • Investigator site 52 - DE0490001
  • Tübingen, Germany, 72076
    • Investigator site 19 - DE0490025
  • Ulm, Germany, 89081
    • Investigator site 93 - DE0490027
  • Würzburg, Germany, 97080
    • Investigator site 4 - DE0490026
• Greece
  • Athens, Greece, 11525
    • Investigator site 21 - GR030004
  • Athens, Greece, 16121
    • Investigator site 37 - GR030006
  • Athens, Greece, 16121
    • Investigator site 54 - GR0300001
  • Chaïdári, Greece, 12462
    • Investigator site 22 - GR030003
  • Thessaloníki, Greece, 54643
    • Investigator site 36 - GR0300002
  • Thessaloníki, Greece, 56429
    • Investigator site 23 - GR030005
• Hungary
  • Debrecen, Hungary, 4032
    • Investigator site 6 - HU0360003
  • Pécs, Hungary, 7632
    • Investigator site 5 - HU0360001
  • Szeged, Hungary, 6720
    • Investigator site 24 - HU0360002
• India
  • Ahmedabad, India, 380016
    • Investigator site 65 - IN0910002
  • Chandigarh, India, 160012
    • Investigator site 94 - IN0910001
  • Lucknow, India, 226005
    • Investigator site 79 - IN0910004
  • Nagpur, India, 440003
    • Investigator site 80 - IN0910003
• Israel
  • Tel Aviv, Israel, 64239
    • Investigator site 85 - IL9720002
• Italy
  • Catania, Italy, 95123
    • Investigator site 95 - IT0390039
  • Firenze, Italy, 50125
    • Investigator site 38 - IT0390031
  • Genova, Italy, 16132
    • Investigator site 81 - IT0390030
  • Perugia, Italy, 06129
    • Investigator site 55 - IT0390038
  • Roma, Italy, 00167
    • Investigator site 12 - IT0390006
  • Roma, Italy, 00168
    • Investigator site 25 - IT-0390005
  • Siena, Italy, 53100
    • Investigator site 61 - IT0390040
• Japan
  • Aichi, Japan, 480-1195
    • Investigator site 82 - JP0810046
  • Hiroshima, Japan, 734-8551
    • Investigator site 68 - JP0810040
  • Kurume, Japan, 830-001
    • Investigator site 69 - JP0810050
  • Kōfu, Japan, 400-8506
    • Investigator site 66 - JP0810042
  • Okayama, Japan, 700-8558
    • Investigator site 73 - JP0810047
  • Okayama, Japan, 701-0192
    • Investigator site 70 - JP0810041
  • Osaka, Japan, 545-8586
    • Investigator site 71 - JP0810049
  • Sapporo, Japan, 060-8648
    • Investigator site 72 - JP0810045
  • Sendai, Japan, 980-8574
    • Investigator site 114 - JP0810067
  • Tokyo, Japan, 113-8431
    • Investigator site 67 - JP0810043
• Poland
  • Katowice, Poland, 40-081
    • Investigator site 27 - PL0480027
  • Poznań, Poland, 60-369
    • Investigator site 86 - PL0480036
  • Rzeszów, Poland, 35-055
    • Investigator site 28 - PL0480025
  • Wrocław, Poland, 50-566
    • Investigator site 26 - PL0480028
  • Łódź, Poland, 90-647
    • Investigator site 56 - PL0480032
• Romania
  • Bucharest, Romania, 011216
    • Investigator site 97 - RO0400013
  • Cluj-Napoca, Romania, 400006
    • Investigator 96 - RO0400014
  • Iaşi, Romania, 700111
    • Investigator site 98 - RO0400015
• Russian Federation
  • Chelyabinsk, Russian Federation, 454092
    • Investigator site 40 - RU0070035
  • Ekaterinburg, Russian Federation, 620076
    • Investigator site 41 - RU0070033
  • Kazan, Russian Federation, 420111
    • Investigator site 48 - RU0070029
  • Krasnodar, Russian Federation, 350020
    • Investigator site 49 - RU0070030
  • Rostov-on-Don, Russian Federation, 344002
    • Investigator site 39 - RU0070032
  • Saint Petersburg, Russian Federation, 191123
    • Investigator site 46 - RU0070031
  • Saint Petersburg, Russian Federation, 197022
    • Investigator site 50 - RU0070034
  • Saratov, Russian Federation, 410012/410028
    • Investigator site 47 - RU0070028
• Serbia
  • Belgrade, Serbia, 11000
    • Investigator site 109 - RS3810011
  • Belgrade, Serbia, 11000
    • Investigator site 110 - RS3810010
  • Niš, Serbia, 18000
    • Investigator site 105 - RS3810012
  • Novi Sad, Serbia, 21000
    • Investigator site 104 - RS3810009
• Spain
  • Barcelona, Spain, 08907
    • Investigator site 62 - ES0340026
  • Barcelona, Spain, 8036
    • Investigator site 13 - ES0340032
  • Granada, Spain, 18016
    • Investigator site 122 - ES0340053
  • Madrid, Spain, 28007
    • Investigator site 59 - ES0340034
  • Madrid, Spain, 28034
    • Investigator site 42 - ES0340025
  • Madrid, Spain, 28041
    • Investigator site 7 - ES0340029
  • Madrid, Spain, 28046
    • Investigator site 57 - ES0340027
  • Sevilla, Spain, 41013
    • Investigator site 58 - ES0340028
• Turkey
  • Gaziantep, Turkey, 27310
    • Investigator site 64 - TR0900020
  • Istanbul, Turkey, 34098
    • Investigator site 63 - TR0900012
  • Istanbul, Turkey, 34722
    • Investigator site 74 - TR0900011
• Ukraine
  • Dnipro, Ukraine, 49074
    • Investigator site 75 - UA3800017
  • Ivano-Frankivs'k, Ukraine, 76018
    • Investigator site 29 - UA3800023
  • Kyiv, Ukraine, 04050
    • Investigator site 14 - UA3800020
  • Kyiv, Ukraine, 4209
    • Investigator site 8 - UA3800019
  • Lviv, Ukraine, 79013
    • Investigator site 43 - UA3800021
  • Zaporizhzhia, Ukraine, 69063
    • Investigator site 9 - UA3800018
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • Investigator site 106 - UK0440021
  • Bristol, United Kingdom, BS2 8HW
    • Investigator site 83 - UK0440022
  • Southampton, United Kingdom, SO16 6YD
    • Investigator site 123 - UK0440037
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Investigator site 115 - US0010086
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Investigator site 89 - US0010091
  • California
    • Redwood City, California, United States, 94063
      • Investigator site 124 - US0010092
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Investigator site 1 - US0010087
    • Miami, Florida, United States, 33173
      • Investigator site 90 - US0010117
    • Orlando, Florida, United States, 32827
      • Investigator site 91 - US0010109
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Investigator site 126 - US0010090
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Investigator site 111 - US0010098
  • New York
    • Buffalo, New York, United States, 14203-1070
      • Investigator site 10 - US0010088
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Investigator site 76 - US0010096
  • Ohio
    • Cleveland, Ohio, United States, 44106-1716
      • Investigator site 30 - US0010094
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Investigator site 84 - US0010089
    • Philadelphia, Pennsylvania, United States, 19140
      • Investigator site 103 - US0010097
  • Texas
    • Dallas, Texas, United States, 75246
      • Investigator site 125 - US0010107
    • Dripping Springs, Texas, United States, 78620
      • Investigator site 87 - US0010084
    • Houston, Texas, United States, 77008
      • Investigator site 88 - US0010114
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Investigator site 44 - US0010106

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 participated in trial ARGX-113-1904 and completed the study or has the defined criteria for rollover.

3. Contraceptive use by men and women should be consistent with local regulations regarding the methods for contraception for those participating in clinical trials and:

   1. Male participants:

      Male participants must agree to use an acceptable method of contraception as described in the protocol, from signing the ICF until the last dose of the study drug.

   2. Female participants

Women of childbearing potential (WOCBP) must:

• have a negative urine pregnancy test at baseline before the IMP can be administered,
• agree to use a highly effective or acceptable contraception method (as described in the protocol), which should be maintained at minimum until after the last dose of IMP

Exclusion Criteria:

1. Pregnant and lactating women and those intending to become pregnant during the trial.
2. 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 participant at undue risk.
3. Known hypersensitivity to any of the components of the administered treatments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: efgartigimod PH20 SC; patients receiving efgartigimod PH20 SC on top of prednisone	Biological: efgartigimod PH20 SC; Subcutaneous injection of efgartigimod using rHuPH20 (PH20) as a permeation enhancer; Drug: prednisone; Oral prednisone tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE)	Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE)	Up to 60 weeks
Severity of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE)	Severity of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE)	Up to 60 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Pemphigus Vulgaris (PV) participants who achieve complete clinical remission (CR) on minimal prednisone therapy	Proportion of participants with Pemphigus Vulgaris who achieve complete clinical remission on minimal prednisone therapy.	Up to 52 weeks treatment period
Proportion of Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF) participants who achieve complete clinical remission (CR) on minimal prednisone dose therapy	Proportion of participants with Pemphigus Vulgaris and Pemphigus Foliaceus who achieve complete clinical remission on minimal prednisone therapy.	Up to 52 weeks treatment period
Time to Disease Control (DC)	Time to Disease Control	Up to 60 weeks
Time to complete clinical remission (CR)	Time to complete clinical remission	Up to 60 weeks
Time to complete clinical remission (CR) on minimal prednisone therapy	Time to complete clinical remission on minimal prednisone therapy	Up to 60 weeks
Time to complete clinical remission (CR) off prednisone therapy	Time to complete clinical remission off prednisone therapy	Up to 60 weeks
Time to flare	Time to flare	Up to 60 weeks
Rate of treatment failure	Rate of treatment failure	Up to 60 weeks
Rate of flare	Rate of flare	Up to 60 weeks
Cumulative prednisone dose over the trial	Cumulative prednisone dose over the trial	Up to 52 weeks treatment period
Pemphigus Disease Area Index (PDAI) at each visit	Pemphigus Disease Area Index at each visit	Up to 52 weeks treatment period
EuroQol 5-Dimension 5-Level (EQ-5D-5L) score	EuroQol 5-Dimension 5-Level score	Up to 52 weeks treatment period
Autoimmune Blister Quality of Life (ABQOL) score	Autoimmune Blister Quality of Life score	Up to 52 weeks treatment period
Efgartigimod serum concentrations	Efgartigimod serum concentrations	Up to 60 weeks
Total Immunoglobulin G and subtype (IgG1, IgG2, IgG3, IgG4) serum levels	Total Immunoglobulin G and subtype (IgG1, IgG2, IgG3, IgG4) serum levels	Up to 60 weeks
Anti-desmoglein (Dsg) -1 and -3 autoantibodies serum levels	Anti-desmoglein (Dsg) -1 and -3 autoantibodies serum levels	Up to 60 weeks
Incidence of antidrug antibodies (ADA) against efgartigimod PH20 SC	Incidence of antidrug antibodies (ADA) against efgartigimod PH20 SC	Up to 60 weeks
Prevalence of antidrug antibodies (ADA) against efgartigimod PH20 SC	Prevalence of antidrug antibodies (ADA) against efgartigimod PH20 SC	Up to 60 weeks
Composite Glucocorticoid Toxicity Index (C-GTI) comprising the Aggregate Improvement Score (AIS) and the Cumulative Worsening Score (CWS)	Composite Glucocorticoid Toxicity Index comprising the Aggregate Improvement Score and the Cumulative Worsening Score	Up to 52 weeks treatment period
Percentage of participants who performed self-administration	Percentage of participants who performed self-administration	Up to 52 weeks
Percentage of caregivers who administered the injection to the participant	Percentage of caregivers who administered the injection to the participant	Up to 52 weeks
Number of visits needed for the participant or caregiver to be competent to start administering efgartigimod PH20 SC	Number of visits needed for the participant or caregiver to be competent to start administering efgartigimod PH20 SC	Up to 52 weeks
Frequency of self- or caregiver-supported administration at home	Frequency of self- or caregiver-supported administration at home	Up to 52 weeks

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2021
• Primary Completion (Estimated): September 24, 2024
• Study Completion (Estimated): November 19, 2024

Study Registration Dates

• First Submitted: October 8, 2020
• First Submitted That Met QC Criteria: October 16, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Skin Diseases, Vesiculobullous; Pemphigus; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: ARGX-113-1905

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No