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

Bullous Pemphigoid Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05267600
• Other study ID #: ARGX-113-2009
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: June 9, 2022
• Est. completion date: March 28, 2025

Study information

• Verified date: January 2024
• Source: argenx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 98
• Est. completion date: March 28, 2025
• Est. primary completion date: February 7, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bullous Pemphigoid
• Pemphigoid, Bullous

Intervention

Biological:
• efgartigimod PH20 SC
Subcutaneous injection of efgartigimod coformulated with rHuPH20, a permeation enhancer

Other:
• placebo
Subcutaneous injection of placebo coformulated with rHuPH20, a permeation enhancer

Drug:
• Prednisone
Oral Prednisone

Locations

Country	Name	City	State
Australia	Investigator site 36 - AU0610013	Fitzroy
Australia	Investigator site 27 - AU0610006	Kogarah
Australia	Investigator site 125 - AU0610019	Woolloongabba
Bulgaria	Investigator site 14 - BG3590010	Sofia
Bulgaria	Investigator site 28 - BG3590018	Sofia
Bulgaria	Investigator site 15 - BG3590020	Stara Zagora
China	Investigator site 111 - CN0860064	Beijing
China	Investigator site 91 - CN0860017	Beijing
China	Investigator site 95 - CN0860018	Chengdu
China	Investigator site 116 - CN0860027	Chongqing
China	Investigator site 108 - CN0860023	Fujian
China	Investigator site 107 - CN0860021	Guangzhou
China	Investigator site 110 - CN0860053	Guanzhou
China	Investigator site 128 - CN0860097	Hefei
China	Investigator site 124 - CN0860098	Nanchang
China	Investigator site 94 - CN0860066	Nanyang
China	Investigator site 127 - CN860020	Shangai
China	Investigator site 123 - CN0860095	Shanghai
China	Investigator site 122 - CN0860065	Ürümqi
China	Investigator site 109 - CN0860025	Wuhan
China	Investigator site 126 - CN0860026	Zhengzhou
Croatia	Investigator site 22 - HR3850003	Split
Croatia	Investigator site 16 - HR3850002	Zagreb
Croatia	Investigator site 37 - HR3850001	Zagreb
Czechia	Investigator site 97 - CZ4200015	Brno
Czechia	Investigator site 118 - CZ4200016	Hradec Králové
Czechia	Investigator site 117 - CZ4200013	Plzen-Bory
Czechia	Investigator site 96 - CZ4200012	Prague
France	Investigator site 38 - FR0330040	Nice
France	Investigator site 29 - FR0330029	Rouen
Germany	Investigator site 46 - DE0490039	Berlin
Germany	Investigator site 54 - DE0490030	Dresden
Germany	Investigator site 80 - DE0490041	Düsseldorf
Germany	Investigator site 57 - DE0490046	Erlangen
Germany	Investigator site 51 - DE0490008	Essen
Germany	Investigator site 52 - DE0490024	Frankfurt am main
Germany	Investigator site 53 - DE0490023	Freiburg
Germany	Investigator site 56 - DE0490028	Kiel
Germany	Investigator site 45 - DE0490001	Marburg
Germany	Investigator site 75 - DE0490047	München
Germany	Investigator site 55 - DE0490026	Würzburg
Greece	Investigator site 58 - GR0300001	Athens
Greece	Investigator site 60 - GE0300004	Athens
Greece	Investigator site 62 - GE0300006	Athens
Greece	Investigator site 76 - GR030003	Chaïdári
Greece	Investigator site 59 - GR0300005	Thessaloníki
Greece	Investigator site 61 - GE0300002	Thessaloníki
Hungary	Investigator site 26 - HU0360023	Budapest
Hungary	Investigator site 11 - HU0360003	Debrecen
Hungary	Investigator site 7 - HU0360008	Pécs
Israel	Investigator site 39 - IL9720003	Afula
Israel	Investigator site 63 - IL9720018	Haifa
Israel	Investigator site 41 - IL9720001	Ramat Gan
Israel	Investigator site 40 - IL9720002	Tel Aviv
Italy	Investigator site 65 - IT0390055	Bologna
Italy	Investigator site 43 - IT0390060	Brescia
Italy	Investigator site 78 - IT0390039	Catania
Italy	Investigator site 47 - IT0390031	Firenze
Italy	Investigator site 86 - IT0390067	Firenze
Italy	Investigator site 81 - IT0390030	Genova
Italy	Investigator site 77 - IT0390062	Milano
Italy	Investigator site 119 - IT0390066	Parma
Italy	Investigator site 64 - IT0390061	Pavia
Italy	Investigator site 23 - IT0390006	Roma
Italy	Investigator site 42 - IT0390005	Roma
Italy	Investigator site 30 - IT0390040	Siena
Japan	Investigator site 103 - JP0810070	Kumamoto
Japan	Investigator site 99 - JP0810050	Kurume
Japan	Investigator site 104 - JP0810071	Maebashi
Japan	Investigator site 100 - JP0810046	Nagakute
Japan	Investigator site 129 - JP0810073	Niigata
Japan	Investigator site 101 - JP0810049	Osaka
Japan	Investigator site 102 - JP0810069	Osaka-sayama
Japan	Investigator site 112 - JP0810045	Sapporo
Japan	Investigator site 105 - JP0810067	Sendai
Japan	Investigator site 98 - JP0810043	Tokyo
Japan	Investigator site 106 - JP0810068	Yokohama
Latvia	Investigator site 82 - LV3710003	Riga
Latvia	Investigator site 87 - LV3710005	Riga
Latvia	Investigator site 88 - LV3710004	Riga
Netherlands	Investigator site 66 - NL0310015	Groningen
Poland	Investigator site 17 - PL0480047	Lódz
Poland	Investigator site 79 - PL0480025	Rzeszów
Poland	Investigator site 83 - PL0480050	Warsaw
Poland	Investigator site 18 - PL0480048	Wroclaw
Poland	Investigator site 19 - PL0480046	Wroclaw
Romania	Investigator site 90 - RO0400014	Cluj-Napoca
Romania	Investigator site 89 - RO0400015	Iasi
Serbia	Investigator site 84 - RS3810010	Belgrad
Serbia	Investigator 68 - RS381011	Belgrade
Serbia	Investigator site 67 - RS3810012	Niš
Serbia	Investigator site 69 - RS3810009	Novi Sad
Slovakia	Investigator site 113 - SK4210002	Bratislava
Slovakia	Investigator site 120 - SK4210004	Košice
Slovakia	Investigator site 114 - SK4210003	Trnava
Spain	Investigator site 32 - ES0340050	Badalona
Spain	Investigator 24 - ES0340051	Barcelona
Spain	Investigator site 8 - ES0340053	Granada
Spain	Investigator 20 - ES0340029	Madrid
Spain	Investigator site 12 - ES0340025	Madrid
Spain	Investigator site 31 - ES0340057	Málaga
Spain	Investigator site 49 - ES0340058	Manises
Spain	Investigator site 48 - ES0340059	Mieres
Spain	Investigator site 9 - ES0340052	Sevilla
Spain	Investigator site 70 - ES0340061	Valencia
United Kingdom	Investigator site 33 - UK0440022	Bristol
United Kingdom	Investigator site 71 - UK0440036	London
United Kingdom	Investigator site 44 - UK0440037	Southampton
United States	Investigator site 50 - US0010149	Ann Arbor	Michigan
United States	Investigator site 2 - US0010087	Boca Raton	Florida
United States	Investigator site 5 - US0010088	Buffalo	New York
United States	Investigator site 10 - US0010153	Castle Rock	Colorado
United States	Investigator site 21 - US0010152	Clearwater	Florida
United States	Investigator site 4 - US0010137	Fairborn	Ohio
United States	Investigator site 6 - US0010138	Fountain Valley	California
United States	Investigator site 34 - US0010182	Houston	Texas
United States	Investigator site 115 - US0010157	Jackson	Mississippi
United States	Investigator site 85 - US0010159	Lebanon	New Hampshire
United States	Investigator site 35 - US0010156	Louisville	Kentucky
United States	Investigator site 1 - US0010017	Miami	Florida
United States	Investigator site 3 - US0010151	Morgantown	West Virginia
United States	Investigator site 92 - US0010150	Murray	Utah
United States	Investigator site 93 - US0010169	New York	New York
United States	Investigator site 74 - US0010178	Phoenix	Arizona
United States	Investigator site 25 - US0010158	Pittsburgh	Pennsylvania
United States	Investigator site 121 - US0010092	Redwood City	California
United States	Investigator site 73 - US0010098	Saint Louis	Missouri
United States	Investigator site 72 - US0010186	Santa Monica	California
United States	Investigator site 13 - US0010155	West Lafayette	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
argenx

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  China,  Croatia,  Czechia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Latvia,  Netherlands,  Poland,  Romania,  Serbia,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Cumulative dose of oral corticosteroid (OCS) from baseline to week 36		up to week 36
Secondary	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
Secondary	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
Secondary	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
Secondary	Changes from baseline in the Bullous Pemphigoid Disease Area Index (BPDAI) activity score		up to week 36
Secondary	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
Secondary	Time to achieve control of disease activity (CDA)		up to week 36
Secondary	Time to achieve complete remission (CR)		up to week 36
Secondary	Time to achieve complete remission (CR) while on minimal oral corticosteroid (OCS) therapy for =8 weeks		up to week 36
Secondary	Time to achieve complete remission (CR)/partial remission (PR) while off oral corticosteroid (OCS) therapy for =8 weeks		up to week 36
Secondary	Time to achieve complete remission (CR) while off oral corticosteroid (OCS) therapy for =8 weeks		up to week 36
Secondary	Time to achieve relapse		up to week 36
Secondary	Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit control of disease activity (CDA)		up to week 36
Secondary	Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit complete remission (CR)		up to week 36
Secondary	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
Secondary	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
Secondary	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
Secondary	Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit relapse		up to week 36
Secondary	Proportion of participants who receive rescue therapy before week 36		at week 36
Secondary	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
Secondary	Changes from baseline in the 24-hour average itch score from the Itch Numerical Rating Scale (Itch NRS)		up to week 36
Secondary	Changes from baseline in the 24-hour worst itch score from the Itch Numerical Rating Scale (Itch NRS)		up to week 36
Secondary	Incidence of treatment emergent adverse events (TEAEs)		up to 46 weeks
Secondary	Severity of treatment emergent adverse events (TEAEs)		up to 46 weeks
Secondary	Incidence of adverse events of special interest (AESIs)		up to 46 weeks
Secondary	Severity of adverse events of special interest (AESIs)		up to 46 weeks
Secondary	Incidence of serious adverse events (SAEs)		up to 46 weeks
Secondary	Severity of serious adverse events (SAEs)		up to 46 weeks
Secondary	The Aggregate Improvement Score (AIS) from the Glucocorticoid Toxicity Index (GTI)		up to week 36
Secondary	The Cumulative Worsening Score (CWS) from the Glucocorticoid Toxicity Index (GTI)		up to week 36
Secondary	The Glucocorticoid Toxicity Index Specific List (GTI-SL)		up to week 36
Secondary	EuroQol 5-Dimension 5-Level (EQ-5D-5L) scores over time		up to week 36
Secondary	Dermatology Life Quality Index (DLQI) scores over time		up to week 36
Secondary	Autoimmune Bullous Disease Quality of Life (ABQoL) scores over time		up to week 36
Secondary	Efgartigimod serum concentrations		up to week 43
Secondary	Percent change of total IgG serum levels from baseline over time		up to 46 weeks
Secondary	Percent change of Anti-BP180 and anti-BP230 antibodies from baseline over time		up to 46 weeks
Secondary	Incidence of Antidrug antibodies (ADA) against efgartigimod (in serum) and antibodies produced against rHuPH20 (in plasma)		up to 46 weeks
Secondary	Number of participants (or their caregivers) who complete the (self-)administration training at study sites		up to week 32
Secondary	Percentage of participants (or their caregivers) who complete the (self-)administration training at study sites		up to week 32
Secondary	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
Secondary	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
Secondary	Number of participants (or their caregivers) who successfully (self-)administer efgartigimod PH20 SC under site staff supervision		up to week 35
Secondary	Percentage of participants (or their caregivers) who successfully (self-)administer efgartigimod PH20 SC under site staff supervision		up to week 35