Clinical trial NCT05267600: A Phase 2/3 Study of Efgartigimod PH20 SC in Adult Participants with Bullous Pemphigoid
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Bullous Pemphigoid
Lead sponsor: argenx
Sponsor class: INDUSTRY
First posted: 2022-03-04
Enrollment: 98
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: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: at week 36
Secondary outcomes:
measure: Cumulative dose of oral corticosteroid (OCS) from baseline to week 36
timeFrame: up to week 36
measure: 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
timeFrame: at week 36
measure: 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
timeFrame: at week 36
measure: 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
timeFrame: up to week 36
measure: Changes from baseline in the Bullous Pemphigoid Disease Area Index (BPDAI) activity score
timeFrame: up to week 36
measure: 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
timeFrame: at week 36
measure: Time to achieve control of disease activity (CDA)
timeFrame: up to week 36
measure: Time to achieve complete remission (CR)
timeFrame: up to week 36
measure: Time to achieve complete remission (CR) while on minimal oral corticosteroid (OCS) therapy for ≥8 weeks
timeFrame: up to week 36
measure: Time to achieve complete remission (CR)/partial remission (PR) while off oral corticosteroid (OCS) therapy for ≥8 weeks
timeFrame: up to week 36
measure: Time to achieve complete remission (CR) while off oral corticosteroid (OCS) therapy for ≥8 weeks
timeFrame: up to week 36
measure: Time to achieve relapse
timeFrame: up to week 36
measure: Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit control of disease activity (CDA)
timeFrame: up to week 36
measure: Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit complete remission (CR)
timeFrame: up to week 36
measure: 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
timeFrame: up to week 36
measure: 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
timeFrame: up to week 36
measure: 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
timeFrame: up to week 36
measure: Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit relapse
timeFrame: up to week 36
measure: Proportion of participants who receive rescue therapy before week 36
timeFrame: at week 36
measure: 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
timeFrame: up to week 36
measure: Changes from baseline in the 24-hour average itch score from the Itch Numerical Rating Scale (Itch NRS)
timeFrame: up to week 36
measure: Changes from baseline in the 24-hour worst itch score from the Itch Numerical Rating Scale (Itch NRS)
timeFrame: up to week 36
measure: Incidence of treatment emergent adverse events (TEAEs)
timeFrame: up to 46 weeks
measure: Severity of treatment emergent adverse events (TEAEs)
timeFrame: up to 46 weeks
measure: Incidence of adverse events of special interest (AESIs)
timeFrame: up to 46 weeks
measure: Severity of adverse events of special interest (AESIs)
timeFrame: up to 46 weeks
measure: Incidence of serious adverse events (SAEs)
timeFrame: up to 46 weeks
measure: Severity of serious adverse events (SAEs)
timeFrame: up to 46 weeks
measure: The Aggregate Improvement Score (AIS) from the Glucocorticoid Toxicity Index (GTI)
timeFrame: up to week 36
measure: The Cumulative Worsening Score (CWS) from the Glucocorticoid Toxicity Index (GTI)
timeFrame: up to week 36
measure: The Glucocorticoid Toxicity Index Specific List (GTI-SL)
timeFrame: up to week 36
measure: EuroQol 5-Dimension 5-Level (EQ-5D-5L) scores over time
timeFrame: up to week 36
measure: Dermatology Life Quality Index (DLQI) scores over time
timeFrame: up to week 36
measure: Autoimmune Bullous Disease Quality of Life (ABQoL) scores over time
timeFrame: up to week 36
measure: Efgartigimod serum concentrations
timeFrame: up to week 43
measure: Percent change of total IgG serum levels from baseline over time
timeFrame: up to 46 weeks
measure: Percent change of Anti-BP180 and anti-BP230 antibodies from baseline over time
timeFrame: up to 46 weeks
measure: Incidence of Antidrug antibodies (ADA) against efgartigimod (in serum) and antibodies produced against rHuPH20 (in plasma)
timeFrame: up to 46 weeks
measure: Number of participants (or their caregivers) who complete the (self-)administration training at study sites
timeFrame: up to week 32
measure: Percentage of participants (or their caregivers) who complete the (self-)administration training at study sites
timeFrame: up to week 32
measure: Number of participants (or their caregivers) who are determined by site staff to be sufficiently competent in (self-)administering efgartigimod PH20 SC
timeFrame: up to week 32
measure: Percentage of participants (or their caregivers) who are determined by site staff to be sufficiently competent in (self-)administering efgartigimod PH20 SC
timeFrame: up to week 32
measure: Number of participants (or their caregivers) who successfully (self-)administer efgartigimod PH20 SC under site staff supervision
timeFrame: up to week 35
measure: Percentage of participants (or their caregivers) who successfully (self-)administer efgartigimod PH20 SC under site staff supervision
timeFrame: up to week 35
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Investigator site 74 - US0010178
state: Arizona
city: Fountain Valley
country: United States
facility: Investigator site 6 - US0010138
state: California
city: Redwood City
country: United States
facility: Investigator site 121 - US0010092
state: California
city: Santa Monica
country: United States
facility: Investigator site 72 - US0010186
state: California
city: Castle Rock
country: United States
facility: Investigator site 10 - US0010153
state: Colorado
city: Boca Raton
country: United States
facility: Investigator site 2 - US0010087
state: Florida
city: Clearwater
country: United States
facility: Investigator site 21 - US0010152
state: Florida
city: Miami
country: United States
facility: Investigator site 1 - US0010017
state: Florida
city: West Lafayette
country: United States
facility: Investigator site 13 - US0010155
state: Indiana
city: Louisville
country: United States
facility: Investigator site 35 - US0010156
state: Kentucky
city: Ann Arbor
country: United States
facility: Investigator site 50 - US0010149
state: Michigan
city: Jackson
country: United States
facility: Investigator site 115 - US0010157
state: Mississippi
city: Saint Louis
country: United States
facility: Investigator site 73 - US0010098
state: Missouri
city: Lebanon
country: United States
facility: Investigator site 85 - US0010159
state: New Hampshire
city: Buffalo
country: United States
facility: Investigator site 5 - US0010088
state: New York
city: New York
country: United States
facility: Investigator site 93 - US0010169
state: New York
city: Fairborn
country: United States
facility: Investigator site 4 - US0010137
state: Ohio
city: Pittsburgh
country: United States
facility: Investigator site 25 - US0010158
state: Pennsylvania
city: Houston
country: United States
facility: Investigator site 34 - US0010182
state: Texas
city: Murray
country: United States
facility: Investigator site 92 - US0010150
state: Utah
city: Morgantown
country: United States
facility: Investigator site 3 - US0010151
state: West Virginia
city: Fitzroy
country: Australia
facility: Investigator site 36 - AU0610013
city: Kogarah
country: Australia
facility: Investigator site 27 - AU0610006
city: Woolloongabba
country: Australia
facility: Investigator site 125 - AU0610019
city: Sofia
country: Bulgaria
facility: Investigator site 28 - BG3590018
city: Sofia
country: Bulgaria
facility: Investigator site 14 - BG3590010
city: Stara Zagora
country: Bulgaria
facility: Investigator site 15 - BG3590020
city: Beijing
country: China
facility: Investigator site 111 - CN0860064
city: Beijing
country: China
facility: Investigator site 91 - CN0860017
city: Chengdu
country: China
facility: Investigator site 95 - CN0860018
city: Chongqing
country: China
facility: Investigator site 116 - CN0860027
city: Fujian
country: China
facility: Investigator site 108 - CN0860023
city: Guangzhou
country: China
facility: Investigator site 107 - CN0860021
city: Guanzhou
country: China
facility: Investigator site 110 - CN0860053
city: Hefei
country: China
facility: Investigator site 128 - CN0860097
city: Nanchang
country: China
facility: Investigator site 124 - CN0860098
city: Nanyang
country: China
facility: Investigator site 94 - CN0860066
city: Shangai
country: China
facility: Investigator site 127 - CN860020
city: Shanghai
country: China
facility: Investigator site 123 - CN0860095
city: Wuhan
country: China
facility: Investigator site 109 - CN0860025
city: Zhengzhou
country: China
facility: Investigator site 126 - CN0860026
city: Ürümqi
country: China
facility: Investigator site 122 - CN0860065
city: Split
country: Croatia
facility: Investigator site 22 - HR3850003
city: Zagreb
country: Croatia
facility: Investigator site 16 - HR3850002
city: Zagreb
country: Croatia
facility: Investigator site 37 - HR3850001
city: Brno
country: Czechia
facility: Investigator site 97 - CZ4200015
city: Hradec Králové
country: Czechia
facility: Investigator site 118 - CZ4200016
city: Plzen-Bory
country: Czechia
facility: Investigator site 117 - CZ4200013
city: Prague
country: Czechia
facility: Investigator site 96 - CZ4200012
city: Nice
country: France
facility: Investigator site 38 - FR0330040
city: Rouen
country: France
facility: Investigator site 29 - FR0330029
city: Berlin
country: Germany
facility: Investigator site 46 - DE0490039
city: Dresden
country: Germany
facility: Investigator site 54 - DE0490030
city: Düsseldorf
country: Germany
facility: Investigator site 80 - DE0490041
city: Erlangen
country: Germany
facility: Investigator site 57 - DE0490046
city: Essen
country: Germany
facility: Investigator site 51 - DE0490008
city: Frankfurt am main
country: Germany
facility: Investigator site 52 - DE0490024
city: Freiburg
country: Germany
facility: Investigator site 53 - DE0490023
city: Kiel
country: Germany
facility: Investigator site 56 - DE0490028
city: Marburg
country: Germany
facility: Investigator site 45 - DE0490001
city: München
country: Germany
facility: Investigator site 75 - DE0490047
city: Würzburg
country: Germany
facility: Investigator site 55 - DE0490026
city: Athens
country: Greece
facility: Investigator site 60 - GE0300004
city: Athens
country: Greece
facility: Investigator site 62 - GE0300006
city: Athens
country: Greece
facility: Investigator site 58 - GR0300001
city: Chaïdári
country: Greece
facility: Investigator site 76 - GR030003
city: Thessaloníki
country: Greece
facility: Investigator site 61 - GE0300002
city: Thessaloníki
country: Greece
facility: Investigator site 59 - GR0300005
city: Budapest
country: Hungary
facility: Investigator site 26 - HU0360023
city: Debrecen
country: Hungary
facility: Investigator site 11 - HU0360003
city: Pécs
country: Hungary
facility: Investigator site 7 - HU0360008
city: Afula
country: Israel
facility: Investigator site 39 - IL9720003
city: Haifa
country: Israel
facility: Investigator site 63 - IL9720018
city: Ramat Gan
country: Israel
facility: Investigator site 41 - IL9720001
city: Tel Aviv
country: Israel
facility: Investigator site 40 - IL9720002
city: Bologna
country: Italy
facility: Investigator site 65 - IT0390055
city: Brescia
country: Italy
facility: Investigator site 43 - IT0390060
city: Catania
country: Italy
facility: Investigator site 78 - IT0390039
city: Firenze
country: Italy
facility: Investigator site 47 - IT0390031
city: Firenze
country: Italy
facility: Investigator site 86 - IT0390067
city: Genova
country: Italy
facility: Investigator site 81 - IT0390030
city: Milano
country: Italy
facility: Investigator site 77 - IT0390062
city: Parma
country: Italy
facility: Investigator site 119 - IT0390066
city: Pavia
country: Italy
facility: Investigator site 64 - IT0390061
city: Roma
country: Italy
facility: Investigator site 23 - IT0390006
city: Roma
country: Italy
facility: Investigator site 42 - IT0390005
city: Siena
country: Italy
facility: Investigator site 30 - IT0390040
city: Kumamoto
country: Japan
facility: Investigator site 103 - JP0810070
city: Kurume
country: Japan
facility: Investigator site 99 - JP0810050
city: Maebashi
country: Japan
facility: Investigator site 104 - JP0810071
city: Nagakute
country: Japan
facility: Investigator site 100 - JP0810046
city: Niigata
country: Japan
facility: Investigator site 129 - JP0810073
city: Osaka
country: Japan
facility: Investigator site 101 - JP0810049
city: Sapporo
country: Japan
facility: Investigator site 112 - JP0810045
city: Sendai
country: Japan
facility: Investigator site 105 - JP0810067
city: Tokyo
country: Japan
facility: Investigator site 98 - JP0810043
city: Yokohama
country: Japan
facility: Investigator site 106 - JP0810068
city: Ōsaka-sayama
country: Japan
facility: Investigator site 102 - JP0810069
city: Riga
country: Latvia
facility: Investigator site 87 - LV3710005
city: Riga
country: Latvia
facility: Investigator site 82 - LV3710003
city: Riga
country: Latvia
facility: Investigator site 88 - LV3710004
city: Groningen
country: Netherlands
facility: Investigator site 66 - NL0310015
city: Rzeszów
country: Poland
facility: Investigator site 79 - PL0480025
city: Warsaw
country: Poland
facility: Investigator site 83 - PL0480050
city: Wrocław
country: Poland
facility: Investigator site 18 - PL0480048
city: Wrocław
country: Poland
facility: Investigator site 19 - PL0480046
city: Łódź
country: Poland
facility: Investigator site 17 - PL0480047
city: Cluj-Napoca
country: Romania
facility: Investigator site 90 - RO0400014
city: Iaşi
country: Romania
facility: Investigator site 89 - RO0400015
city: Belgrade
country: Serbia
facility: Investigator 68 - RS381011
city: Belgrad
country: Serbia
facility: Investigator site 84 - RS3810010
city: Niš
country: Serbia
facility: Investigator site 67 - RS3810012
city: Novi Sad
country: Serbia
facility: Investigator site 69 - RS3810009
city: Bratislava
country: Slovakia
facility: Investigator site 113 - SK4210002
city: Košice
country: Slovakia
facility: Investigator site 120 - SK4210004
city: Trnava
country: Slovakia
facility: Investigator site 114 - SK4210003
city: Badalona
country: Spain
facility: Investigator site 32 - ES0340050
city: Barcelona
country: Spain
facility: Investigator 24 - ES0340051
city: Granada
country: Spain
facility: Investigator site 8 - ES0340053
city: Madrid
country: Spain
facility: Investigator site 12 - ES0340025
city: Madrid
country: Spain
facility: Investigator 20 - ES0340029
city: Manises
country: Spain
facility: Investigator site 49 - ES0340058
city: Mieres
country: Spain
facility: Investigator site 48 - ES0340059
city: Málaga
country: Spain
facility: Investigator site 31 - ES0340057
city: Sevilla
country: Spain
facility: Investigator site 9 - ES0340052
city: Valencia
country: Spain
facility: Investigator site 70 - ES0340061
city: Bristol
country: United Kingdom
facility: Investigator site 33 - UK0440022
city: London
country: United Kingdom
facility: Investigator site 71 - UK0440036
city: Southampton
country: United Kingdom
facility: Investigator site 44 - UK0440037
Study officials:
References: