A Phase 2/3 Study of Efgartigimod PH20 SC in Adult Participants With Bullous Pemphigoid (BALLAD)

A Phase 2/3, Randomized, Double-Blinded, Placebo-Controlled, Parallel-Group Study to Investigate the Efficacy and Safety of Efgartigimod PH20 SC in Adult Participants With Bullous Pemphigoid

ARGX-113-2009 is an operationally seamless 2-part, phase 2/3, prospective, global, multicenter, randomized, double-blinded, placebo-controlled study to investigate the efficacy, safety, tolerability, immunogenicity, participant-reported outcome measures (including those assessing participant QoL), PK, and PD of efgartigimod PH20 SC administered via subcutaneous (SC) injection in adult participants with moderate to severe BP. This study intends to demonstrate that efgartigimod is an effective and safe treatment for BP, providing participants with control of disease activity (CDA) and eventually remission while reducing their cumulative exposure to OCS.

study will consist of 2 parts:

• Part A of the study is a phase 2 evaluation that intends to provide proof of concept for the therapeutic activity of efgartigimod PH20 SC in participants with BP.
• Part B of the study is a phase 3 evaluation that intends to confirm the results obtained from part A in a separate, larger group of participants with BP.

An interim analysis will be performed during part A (on data obtained through week 26 for all Part A participants) to assess the primary endpoint and several secondary endpoints, confirm the appropriate sample size for part B of the study, and determine whether the efficacy results observed through week 26 of part A warrant continued study of efgartigimod PH20 SC for the treatment of participants with BP (futility analysis).

Other than differences in main goals, endpoints, and statistical analyses, parts A and B are identical in schedule, structure, assessments, and conduct.

Study Overview

• Status: Active, not recruiting
• Conditions: Bullous Pemphigoid
• Intervention / Treatment: Biological: efgartigimod PH20 SC; Drug: Prednisone; Other: placebo

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Fitzroy, Australia, 3065
    • Investigator site 36 - AU0610013
  • Kogarah, Australia, 2217
    • Investigator site 27 - AU0610006
  • Woolloongabba, Australia, 4102
    • Investigator site 125 - AU0610019
• Bulgaria
  • Sofia, Bulgaria, 1407
    • Investigator site 28 - BG3590018
  • Sofia, Bulgaria, 1431
    • Investigator site 14 - BG3590010
  • Stara Zagora, Bulgaria, 6003
    • Investigator site 15 - BG3590020
• China
  • Beijing, China, 100006
    • Investigator site 111 - CN0860064
  • Beijing, China
    • Investigator site 91 - CN0860017
  • Chengdu, China
    • Investigator site 95 - CN0860018
  • Chongqing, China, 400016
    • Investigator site 116 - CN0860027
  • Fujian, China, 350004
    • Investigator site 108 - CN0860023
  • Guangzhou, China, 510091
    • Investigator site 107 - CN0860021
  • Guanzhou, China, 510080
    • Investigator site 110 - CN0860053
  • Hefei, China
    • Investigator site 128 - CN0860097
  • Nanchang, China, 330000
    • Investigator site 124 - CN0860098
  • Nanyang, China
    • Investigator site 94 - CN0860066
  • Shangai, China, 200025
    • Investigator site 127 - CN860020
  • Shanghai, China, 200435
    • Investigator site 123 - CN0860095
  • Wuhan, China, 430031
    • Investigator site 109 - CN0860025
  • Zhengzhou, China, 450003
    • Investigator site 126 - CN0860026
  • Ürümqi, China, 830054
    • Investigator site 122 - CN0860065
• Croatia
  • Split, Croatia, 21000
    • Investigator site 22 - HR3850003
  • Zagreb, Croatia, 10000
    • Investigator site 16 - HR3850002
  • Zagreb, Croatia, 10000
    • Investigator site 37 - HR3850001
• Czechia
  • Brno, Czechia, 656 91
    • Investigator site 97 - CZ4200015
  • Hradec Králové, Czechia, 500 05
    • Investigator site 118 - CZ4200016
  • Plzen-Bory, Czechia, 13, 301 00
    • Investigator site 117 - CZ4200013
  • Prague, Czechia, 180 81
    • Investigator site 96 - CZ4200012
• France
  • Nice, France, 06202
    • Investigator site 38 - FR0330040
  • Rouen, France, 76031
    • Investigator site 29 - FR0330029
• Germany
  • Berlin, Germany, 10117
    • Investigator site 46 - DE0490039
  • Dresden, Germany, 01307
    • Investigator site 54 - DE0490030
  • Düsseldorf, Germany, 40225
    • Investigator site 80 - DE0490041
  • Erlangen, Germany, 91054
    • Investigator site 57 - DE0490046
  • Essen, Germany, 45147
    • Investigator site 51 - DE0490008
  • Frankfurt am main, Germany, 60590
    • Investigator site 52 - DE0490024
  • Freiburg, Germany, 79104
    • Investigator site 53 - DE0490023
  • Kiel, Germany, 24105
    • Investigator site 56 - DE0490028
  • Marburg, Germany, 35043
    • Investigator site 45 - DE0490001
  • München, Germany, 85006
    • Investigator site 75 - DE0490047
  • Würzburg, Germany, 97080
    • Investigator site 55 - DE0490026
• Greece
  • Athens, Greece, 11525
    • Investigator site 60 - GE0300004
  • Athens, Greece, 11525
    • Investigator site 62 - GE0300006
  • Athens, Greece, 16121
    • Investigator site 58 - GR0300001
  • Chaïdári, Greece, 12462
    • Investigator site 76 - GR030003
  • Thessaloníki, Greece, 54643
    • Investigator site 61 - GE0300002
  • Thessaloníki, Greece, 56429
    • Investigator site 59 - GR0300005
• Hungary
  • Budapest, Hungary, 1085
    • Investigator site 26 - HU0360023
  • Debrecen, Hungary, 4032
    • Investigator site 11 - HU0360003
  • Pécs, Hungary, 7632
    • Investigator site 7 - HU0360008
• Israel
  • Afula, Israel, 1834111
    • Investigator site 39 - IL9720003
  • Haifa, Israel, 3109601
    • Investigator site 63 - IL9720018
  • Ramat Gan, Israel, 5262100
    • Investigator site 41 - IL9720001
  • Tel Aviv, Israel, 64239
    • Investigator site 40 - IL9720002
• Italy
  • Bologna, Italy, 40138
    • Investigator site 65 - IT0390055
  • Brescia, Italy, 25132
    • Investigator site 43 - IT0390060
  • Catania, Italy, 95123
    • Investigator site 78 - IT0390039
  • Firenze, Italy, 50122
    • Investigator site 47 - IT0390031
  • Firenze, Italy, 50122
    • Investigator site 86 - IT0390067
  • Genova, Italy, 16132
    • Investigator site 81 - IT0390030
  • Milano, Italy, 20122
    • Investigator site 77 - IT0390062
  • Parma, Italy, 43126
    • Investigator site 119 - IT0390066
  • Pavia, Italy, 27100
    • Investigator site 64 - IT0390061
  • Roma, Italy, 00167
    • Investigator site 23 - IT0390006
  • Roma, Italy, 00168
    • Investigator site 42 - IT0390005
  • Siena, Italy, 53100
    • Investigator site 30 - IT0390040
• Japan
  • Kumamoto, Japan, 860-8556
    • Investigator site 103 - JP0810070
  • Kurume, Japan, 830-0011
    • Investigator site 99 - JP0810050
  • Maebashi, Japan, 371-8511
    • Investigator site 104 - JP0810071
  • Nagakute, Japan, 480-1195
    • Investigator site 100 - JP0810046
  • Niigata, Japan, 951-8520
    • Investigator site 129 - JP0810073
  • Osaka, Japan, 545-8586
    • Investigator site 101 - JP0810049
  • Sapporo, Japan, 060-8648
    • Investigator site 112 - JP0810045
  • Sendai, Japan, 980-8574
    • Investigator site 105 - JP0810067
  • Tokyo, Japan, 113-8431
    • Investigator site 98 - JP0810043
  • Yokohama, Japan, 236-0004
    • Investigator site 106 - JP0810068
  • Ōsaka-sayama, Japan, 589-8511
    • Investigator site 102 - JP0810069
• Latvia
  • Riga, Latvia, 1001
    • Investigator site 87 - LV3710005
  • Riga, Latvia, 1003
    • Investigator site 82 - LV3710003
  • Riga, Latvia, 1003
    • Investigator site 88 - LV3710004
• Netherlands
  • Groningen, Netherlands, 9713
    • Investigator site 66 - NL0310015
• Poland
  • Rzeszów, Poland, 35055
    • Investigator site 79 - PL0480025
  • Warsaw, Poland, 00-716
    • Investigator site 83 - PL0480050
  • Wrocław, Poland, 50-220
    • Investigator site 18 - PL0480048
  • Wrocław, Poland, 51-685
    • Investigator site 19 - PL0480046
  • Łódź, Poland, 90-647
    • Investigator site 17 - PL0480047
• Romania
  • Cluj-Napoca, Romania, 400006
    • Investigator site 90 - RO0400014
  • Iaşi, Romania, 700111
    • Investigator site 89 - RO0400015
• Serbia
  • Belgrad, Serbia, 11040
    • Investigator site 84 - RS3810010
  • Belgrade, Serbia, 110000
    • Investigator 68 - RS381011
  • Niš, Serbia, 18000
    • Investigator site 67 - RS3810012
  • Novi Sad, Serbia, 21000
    • Investigator site 69 - RS3810009
• Slovakia
  • Bratislava, Slovakia, 4210002
    • Investigator site 113 - SK4210002
  • Košice, Slovakia, 040 11
    • Investigator site 120 - SK4210004
  • Trnava, Slovakia, 91702
    • Investigator site 114 - SK4210003
• Spain
  • Badalona, Spain, 08916
    • Investigator site 32 - ES0340050
  • Barcelona, Spain, 08003
    • Investigator 24 - ES0340051
  • Granada, Spain, 18016
    • Investigator site 8 - ES0340053
  • Madrid, Spain, 28034
    • Investigator site 12 - ES0340025
  • Madrid, Spain, 28041
    • Investigator 20 - ES0340029
  • Manises, Spain, 46940
    • Investigator site 49 - ES0340058
  • Mieres, Spain, 33611
    • Investigator site 48 - ES0340059
  • Málaga, Spain, 29009
    • Investigator site 31 - ES0340057
  • Sevilla, Spain, 41009
    • Investigator site 9 - ES0340052
  • Valencia, Spain, 46017
    • Investigator site 70 - ES0340061
• United Kingdom
  • Bristol, United Kingdom, BS2 8HW
    • Investigator site 33 - UK0440022
  • London, United Kingdom
    • Investigator site 71 - UK0440036
  • Southampton, United Kingdom, SO16 6YD
    • Investigator site 44 - UK0440037
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Investigator site 74 - US0010178
  • California
    • Fountain Valley, California, United States, 92708
      • Investigator site 6 - US0010138
    • Redwood City, California, United States, 94063
      • Investigator site 121 - US0010092
    • Santa Monica, California, United States, 90404
      • Investigator site 72 - US0010186
  • Colorado
    • Castle Rock, Colorado, United States, 80109
      • Investigator site 10 - US0010153
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Investigator site 2 - US0010087
    • Clearwater, Florida, United States, 33756
      • Investigator site 21 - US0010152
    • Miami, Florida, United States, 33173
      • Investigator site 1 - US0010017
  • Indiana
    • West Lafayette, Indiana, United States, 47906
      • Investigator site 13 - US0010155
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Investigator site 35 - US0010156
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Investigator site 50 - US0010149
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Investigator site 115 - US0010157
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Investigator site 73 - US0010098
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Investigator site 85 - US0010159
  • New York
    • Buffalo, New York, United States, 14203
      • Investigator site 5 - US0010088
    • New York, New York, United States, 10016
      • Investigator site 93 - US0010169
  • Ohio
    • Fairborn, Ohio, United States, 45324
      • Investigator site 4 - US0010137
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Investigator site 25 - US0010158
  • Texas
    • Houston, Texas, United States, 77004
      • Investigator site 34 - US0010182
  • Utah
    • Murray, Utah, United States, 84107
      • Investigator site 92 - US0010150
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Investigator site 3 - US0010151

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The participant is willing and able to do the following:

  1. understand the requirements of the study
  2. provide written informed consent
  3. comply with the study protocol procedures.
• The participant is male or female and has reached the age of consent at the time of signing the informed consent form (ICF).
• Participants have clinical signs of BP.
• Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and: Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before study intervention can be administered.

The full list of inclusion criteria can be found in the protocol.

Exclusion Criteria:

• Other forms of pemphigoid or other autoimmune bullous diseases (AIBDs).
• Received unstable dose of treatments known to cause or exacerbate BP for at least 4 weeks prior to the baseline visit
• Use of BP treatments other than oral corticosteroids (OCS), topical corticosteroids (TCS), conventional immunosuppressants or dapsone.
• Known contraindication to OCS therapy
• Active, chronic or latent infection at screening
• Positive COVID-19 test result at screening (testing performed if required per local regulations).
• History of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before the first administration of the IMP. Participants with 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
• Clinical evidence of other significant serious diseases, have had a recent surgery, or who have any other condition that, in the opinion of the investigator, could confound the results of the study or put the patient at undue risk or prevent participants from complying with protocol requirements
• Use of an investigational product within 3 months before the first dose of IMP
• Previously participated in a clinical study with efgartigimod or currently participating in another interventional clinical study
• Known hypersensitivity to any of the components of the administered treatments
• Positive serum test at screening for an active infection: HBV, HCV, HIV
• Current or history (ie, within 12 months of screening) of alcohol, drug, or medication abuse as assessed by the investigator
• Pregnant or lactating females and those who intend to become pregnant during the study
• Live or live-attenuated vaccine received <4 weeks before baseline visit

The full list of exclusion criteria can be found in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: efgartigimod PH20 SC; participants receiving efgartigimod PH20 SC on top of Prednisone	Biological: efgartigimod PH20 SC; Subcutaneous injection of efgartigimod coformulated with rHuPH20, a permeation enhancer; Drug: Prednisone; Oral Prednisone
Placebo Comparator: placebo PH20 SC; participants receiving placebo PH20 SC on top of Prednisone	Drug: Prednisone; Oral Prednisone; Other: placebo; Subcutaneous injection of placebo coformulated with rHuPH20, a permeation enhancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of participants who are in complete remission (CR) while receiving efgartigimod PH20 SC or placebo and have been off oral corticosteroid (OCS) therapy for ≥8 weeks at week 36	at week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative dose of oral corticosteroid (OCS) from baseline to week 36		up to week 36
Proportion of participants who achieve an Investigator Global Assessment of Bullous Pemphigoid (IGA-BP) score of 0 while receiving efgartigimod PH20 SC or placebo and have been off oral corticosteroid (OCS) therapy for ≥8 weeks at week 36		at week 36
Proportion of participants who achieve an Investigator Global Assessment of Bullous Pemphigoid (IGA-BP) score of 0 or 1 while receiving efgartigimod PH20 SC or placebo and have been off oral corticosteroid (OCS) therapy for ≥8 weeks at week 36		at week 36
Proportion of participants who achieve an Investigator Global Assessment of Bullous Pemphigoid (IGA-BP) score of 0 or 1 while receiving efgartigimod PH20 SC or placebo at any time through week 36		up to week 36
Changes from baseline in the Bullous Pemphigoid Disease Area Index (BPDAI) activity score		up to week 36
Proportion of participants who are in complete remission (CR) while receiving efgartigimod PH20 SC or placebo and have been receiving minimal oral corticosteroid (OCS) therapy for ≥8 weeks at week 36	Minimal oral corticosteroid (OCS) therapy is defined as ≤0.1 mg/kg/day of prednisone (or an equivalent dose of another OCS).	at week 36
Time to achieve control of disease activity (CDA)		up to week 36
Time to achieve complete remission (CR)		up to week 36
Time to achieve complete remission (CR) while on minimal oral corticosteroid (OCS) therapy for ≥8 weeks		up to week 36
Time to achieve complete remission (CR)/partial remission (PR) while off oral corticosteroid (OCS) therapy for ≥8 weeks		up to week 36
Time to achieve complete remission (CR) while off oral corticosteroid (OCS) therapy for ≥8 weeks		up to week 36
Time to achieve relapse		up to week 36
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit control of disease activity (CDA)		up to week 36
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit complete remission (CR)		up to week 36
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit complete remission (CR) while on minimal oral corticosteroid (OCS) therapy for ≥8 weeks		up to week 36
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit complete remission (CR)/partial remission (PR) while off oral corticosteroid (OCS) therapy for ≥8 weeks		up to week 36
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit complete remission (CR) while off oral corticosteroid (OCS) therapy for ≥8 weeks		up to week 36
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit relapse		up to week 36
Proportion of participants who receive rescue therapy before week 36		at week 36
Proportion of participants who achieve control of disease activity (CDA) while receiving efgartigimod PH20 SC or placebo and remain free of relapse through week 36		up to week 36
Changes from baseline in the 24-hour average itch score from the Itch Numerical Rating Scale (Itch NRS)		up to week 36
Changes from baseline in the 24-hour worst itch score from the Itch Numerical Rating Scale (Itch NRS)		up to week 36
Incidence of treatment emergent adverse events (TEAEs)		up to 46 weeks
Severity of treatment emergent adverse events (TEAEs)		up to 46 weeks
Incidence of adverse events of special interest (AESIs)		up to 46 weeks
Severity of adverse events of special interest (AESIs)		up to 46 weeks
Incidence of serious adverse events (SAEs)		up to 46 weeks
Severity of serious adverse events (SAEs)		up to 46 weeks
The Aggregate Improvement Score (AIS) from the Glucocorticoid Toxicity Index (GTI)		up to week 36
The Cumulative Worsening Score (CWS) from the Glucocorticoid Toxicity Index (GTI)		up to week 36
The Glucocorticoid Toxicity Index Specific List (GTI-SL)		up to week 36
EuroQol 5-Dimension 5-Level (EQ-5D-5L) scores over time		up to week 36
Dermatology Life Quality Index (DLQI) scores over time		up to week 36
Autoimmune Bullous Disease Quality of Life (ABQoL) scores over time		up to week 36
Efgartigimod serum concentrations		up to week 43
Number of participants (or their caregivers) who complete the (self-)administration training at study sites		up to week 32
Percentage of participants (or their caregivers) who complete the (self-)administration training at study sites		up to week 32
Number of participants (or their caregivers) who are determined by site staff to be sufficiently competent in (self-)administering efgartigimod PH20 SC		up to week 32
Percentage of participants (or their caregivers) who are determined by site staff to be sufficiently competent in (self-)administering efgartigimod PH20 SC		up to week 32
Number of participants (or their caregivers) who successfully (self-)administer efgartigimod PH20 SC under site staff supervision		up to week 35
Percentage of participants (or their caregivers) who successfully (self-)administer efgartigimod PH20 SC under site staff supervision		up to week 35
Percent change of total IgG serum levels from baseline over time		up to 46 weeks
Percent change of Anti-BP180 and anti-BP230 antibodies from baseline over time		up to 46 weeks
Incidence of Antidrug antibodies (ADA) against efgartigimod (in serum) and antibodies produced against rHuPH20 (in plasma)		up to 46 weeks

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2022
• Primary Completion (Estimated): February 7, 2025
• Study Completion (Estimated): March 28, 2025

Study Registration Dates

• First Submitted: February 14, 2022
• First Submitted That Met QC Criteria: February 23, 2022
• First Posted (Actual): March 4, 2022

Study Record Updates

• Last Update Posted (Estimated): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 16, 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; Pemphigoid, Bullous; 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-113-2009

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No