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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05267600




Registration number
NCT05267600
Ethics application status
Date submitted
14/02/2022
Date registered
4/03/2022
Date last updated
17/01/2024

Titles & IDs
Public title
A Phase 2/3 Study of Efgartigimod PH20 SC in Adult Participants With Bullous Pemphigoid (BALLAD)
Scientific 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
Secondary ID [1] 0 0
ARGX-113-2009
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bullous Pemphigoid 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - efgartigimod PH20 SC
Other interventions - placebo
Treatment: Drugs - Prednisone

Experimental: efgartigimod PH20 SC - participants receiving efgartigimod PH20 SC on top of Prednisone

Placebo comparator: placebo PH20 SC - participants receiving placebo PH20 SC on top of Prednisone


Treatment: Other: efgartigimod PH20 SC
Subcutaneous injection of efgartigimod coformulated with rHuPH20, a permeation enhancer

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

Treatment: Drugs: Prednisone
Oral Prednisone
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
at week 36
Secondary outcome [1] 0 0
Cumulative dose of oral corticosteroid (OCS) from baseline to week 36
Timepoint [1] 0 0
up to week 36
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
at week 36
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
at week 36
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
up to week 36
Secondary outcome [5] 0 0
Changes from baseline in the Bullous Pemphigoid Disease Area Index (BPDAI) activity score
Timepoint [5] 0 0
up to week 36
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
at week 36
Secondary outcome [7] 0 0
Time to achieve control of disease activity (CDA)
Timepoint [7] 0 0
up to week 36
Secondary outcome [8] 0 0
Time to achieve complete remission (CR)
Timepoint [8] 0 0
up to week 36
Secondary outcome [9] 0 0
Time to achieve complete remission (CR) while on minimal oral corticosteroid (OCS) therapy for =8 weeks
Timepoint [9] 0 0
up to week 36
Secondary outcome [10] 0 0
Time to achieve complete remission (CR)/partial remission (PR) while off oral corticosteroid (OCS) therapy for =8 weeks
Timepoint [10] 0 0
up to week 36
Secondary outcome [11] 0 0
Time to achieve complete remission (CR) while off oral corticosteroid (OCS) therapy for =8 weeks
Timepoint [11] 0 0
up to week 36
Secondary outcome [12] 0 0
Time to achieve relapse
Timepoint [12] 0 0
up to week 36
Secondary outcome [13] 0 0
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit control of disease activity (CDA)
Timepoint [13] 0 0
up to week 36
Secondary outcome [14] 0 0
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit complete remission (CR)
Timepoint [14] 0 0
up to week 36
Secondary outcome [15] 0 0
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
Timepoint [15] 0 0
up to week 36
Secondary outcome [16] 0 0
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
Timepoint [16] 0 0
up to week 36
Secondary outcome [17] 0 0
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
Timepoint [17] 0 0
up to week 36
Secondary outcome [18] 0 0
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit relapse
Timepoint [18] 0 0
up to week 36
Secondary outcome [19] 0 0
Proportion of participants who receive rescue therapy before week 36
Timepoint [19] 0 0
at week 36
Secondary outcome [20] 0 0
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
Timepoint [20] 0 0
up to week 36
Secondary outcome [21] 0 0
Changes from baseline in the 24-hour average itch score from the Itch Numerical Rating Scale (Itch NRS)
Timepoint [21] 0 0
up to week 36
Secondary outcome [22] 0 0
Changes from baseline in the 24-hour worst itch score from the Itch Numerical Rating Scale (Itch NRS)
Timepoint [22] 0 0
up to week 36
Secondary outcome [23] 0 0
Incidence of treatment emergent adverse events (TEAEs)
Timepoint [23] 0 0
up to 46 weeks
Secondary outcome [24] 0 0
Severity of treatment emergent adverse events (TEAEs)
Timepoint [24] 0 0
up to 46 weeks
Secondary outcome [25] 0 0
Incidence of adverse events of special interest (AESIs)
Timepoint [25] 0 0
up to 46 weeks
Secondary outcome [26] 0 0
Severity of adverse events of special interest (AESIs)
Timepoint [26] 0 0
up to 46 weeks
Secondary outcome [27] 0 0
Incidence of serious adverse events (SAEs)
Timepoint [27] 0 0
up to 46 weeks
Secondary outcome [28] 0 0
Severity of serious adverse events (SAEs)
Timepoint [28] 0 0
up to 46 weeks
Secondary outcome [29] 0 0
The Aggregate Improvement Score (AIS) from the Glucocorticoid Toxicity Index (GTI)
Timepoint [29] 0 0
up to week 36
Secondary outcome [30] 0 0
The Cumulative Worsening Score (CWS) from the Glucocorticoid Toxicity Index (GTI)
Timepoint [30] 0 0
up to week 36
Secondary outcome [31] 0 0
The Glucocorticoid Toxicity Index Specific List (GTI-SL)
Timepoint [31] 0 0
up to week 36
Secondary outcome [32] 0 0
EuroQol 5-Dimension 5-Level (EQ-5D-5L) scores over time
Timepoint [32] 0 0
up to week 36
Secondary outcome [33] 0 0
Dermatology Life Quality Index (DLQI) scores over time
Timepoint [33] 0 0
up to week 36
Secondary outcome [34] 0 0
Autoimmune Bullous Disease Quality of Life (ABQoL) scores over time
Timepoint [34] 0 0
up to week 36
Secondary outcome [35] 0 0
Efgartigimod serum concentrations
Timepoint [35] 0 0
up to week 43
Secondary outcome [36] 0 0
Percent change of total IgG serum levels from baseline over time
Timepoint [36] 0 0
up to 46 weeks
Secondary outcome [37] 0 0
Percent change of Anti-BP180 and anti-BP230 antibodies from baseline over time
Timepoint [37] 0 0
up to 46 weeks
Secondary outcome [38] 0 0
Incidence of Antidrug antibodies (ADA) against efgartigimod (in serum) and antibodies produced against rHuPH20 (in plasma)
Timepoint [38] 0 0
up to 46 weeks
Secondary outcome [39] 0 0
Number of participants (or their caregivers) who complete the (self-)administration training at study sites
Timepoint [39] 0 0
up to week 32
Secondary outcome [40] 0 0
Percentage of participants (or their caregivers) who complete the (self-)administration training at study sites
Timepoint [40] 0 0
up to week 32
Secondary outcome [41] 0 0
Number of participants (or their caregivers) who are determined by site staff to be sufficiently competent in (self-)administering efgartigimod PH20 SC
Timepoint [41] 0 0
up to week 32
Secondary outcome [42] 0 0
Percentage of participants (or their caregivers) who are determined by site staff to be sufficiently competent in (self-)administering efgartigimod PH20 SC
Timepoint [42] 0 0
up to week 32
Secondary outcome [43] 0 0
Number of participants (or their caregivers) who successfully (self-)administer efgartigimod PH20 SC under site staff supervision
Timepoint [43] 0 0
up to week 35
Secondary outcome [44] 0 0
Percentage of participants (or their caregivers) who successfully (self-)administer efgartigimod PH20 SC under site staff supervision
Timepoint [44] 0 0
up to week 35

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/06/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/03/2025
Actual
Sample size
Target
Accrual to date
Final
98
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigator site 36 - AU0610013 - Fitzroy
Recruitment hospital [2] 0 0
Investigator site 27 - AU0610006 - Kogarah
Recruitment hospital [3] 0 0
Investigator site 125 - AU0610019 - Woolloongabba
Recruitment postcode(s) [1] 0 0
3065 - Fitzroy
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
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California
Country [3] 0 0
United States of America
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Colorado
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United States of America
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Florida
Country [5] 0 0
United States of America
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Indiana
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Kentucky
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United States of America
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Michigan
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Mississippi
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Missouri
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New Hampshire
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New York
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Ohio
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United States of America
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Pennsylvania
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Texas
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Utah
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United States of America
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West Virginia
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Bulgaria
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Sofia
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Bulgaria
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Stara Zagora
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China
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Beijing
Country [20] 0 0
China
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Chengdu
Country [21] 0 0
China
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Chongqing
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Fujian
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Guangzhou
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Guanzhou
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Hefei
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Nanchang
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Nanyang
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Shangai
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Wuhan
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Zhengzhou
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China
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Ürümqi
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Split
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Zagreb
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Brno
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Hradec Králové
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Plzen-Bory
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Prague
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Erlangen
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Essen
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Germany
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Frankfurt am main
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Freiburg
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Kiel
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Marburg
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München
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Athens
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Pécs
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Afula
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Israel
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Haifa
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Ramat Gan
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Bologna
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Brescia
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Italy
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Catania
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Italy
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Firenze
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Italy
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Genova
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Milano
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Italy
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Parma
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Pavia
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Roma
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Siena
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Kumamoto
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Kurume
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Maebashi
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Niigata
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Sapporo
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Osaka-sayama
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Latvia
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Riga
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Netherlands
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Groningen
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Poland
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Rzeszów
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Warsaw
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Wroclaw
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Poland
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Lódz
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Romania
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Cluj-Napoca
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Romania
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Iasi
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Serbia
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Belgrade
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Serbia
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Belgrad
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Serbia
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Niš
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Serbia
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Novi Sad
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Slovakia
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Bratislava
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Slovakia
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Košice
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Slovakia
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Trnava
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Spain
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Badalona
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Spain
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Barcelona
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Spain
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Granada
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Spain
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Madrid
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Spain
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Manises
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Spain
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Mieres
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Spain
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Málaga
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Spain
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Sevilla
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Spain
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Valencia
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United Kingdom
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Bristol
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United Kingdom
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London
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United Kingdom
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Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
argenx
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05267600
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05267600