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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Bullous Pemphigoid

Intervention / Treatment
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* Biological: efgartigimod PH20 SC
* Other: placebo
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant is willing and able to do the following: understand the requirements of the study provide written informed consent 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 
| 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 | 
| 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 |