A Phase 2/3 Study of Efgartigimod PH20 SC in Adult Participants With Bullous Pemphigoid (BALLAD)
Study Details
Study Description
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:
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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.
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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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Study Design
Arms and Interventions
| 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 |
Other: placebo
Subcutaneous injection of placebo coformulated with rHuPH20, a permeation enhancer
Drug: Prednisone
Oral Prednisone
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 [up to 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 [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).
- 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]
- Total IgG serum levels [up to 46 weeks]
- Anti-BP180 and anti-BP230 antibodies [up to 46 weeks]
- Antidrug antibodies (ADA) to 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
- The participant is willing and able to do the following:
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understand the requirements of the study
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provide written informed consent
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comply with the study protocol procedures.
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The participant is male or female and has reached the age of consent at the time of signing the informed consent form (ICF).
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Participants have clinical signs of BP.
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Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and:
- Male participants:
- Must agree to use an acceptable method of contraception from the time that the ICF is signed until the date of their last dose of IMP.
- Female participants:
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Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before study intervention can be administered.
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WOCBP must agree to use at least one of the contraception methods identified in the protocol from the time that the ICF is signed until the date of their last dose of IMP.
The full list of inclusion criteria can be found in the protocol.
Exclusion Criteria:
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Other forms of pemphigoid or other autoimmune bullous diseases (AIBDs).
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Received unstable dose of treatments known to cause or exacerbate BP for at least 4 weeks prior to the baseline visit
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Use of BP treatments other than oral corticosteroids (OCS), topical corticosteroids (TCS), conventional immunosuppressants or dapsone.
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Known contraindication to OCS therapy
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Active or chronic infection at screening
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Positive COVID-19 test result at screening (testing performed if required per local regulations).
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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:
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Basal cell or squamous cell skin cancer
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Carcinoma in situ of the cervix
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Carcinoma in situ of the breast
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Incidental histological finding of prostate cancer
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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
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Use of an investigational product within 3 months before the first dose of IMP
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Previously participated in a clinical study with efgartigimod
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Known hypersensitivity to any of the components of the administered treatments
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Positive serum test at screening for an active infection:
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HBV
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HCV
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HIV
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Current or history (ie, within 12 months of screening) of alcohol, drug, or medication abuse
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Pregnant or lactating females and those who intend to become pregnant during the study
The full list of exclusion criteria can be found in the protocol.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigator site 6 - US0010138 | Fountain Valley | California | United States | 92708 |
| 2 | Investigator site 10 - US0010153 | Castle Rock | Colorado | United States | 80109 |
| 3 | Investigator site 2 - US0010087 | Boca Raton | Florida | United States | 33428 |
| 4 | Investigator site 21 - US0010155 | Clearwater | Florida | United States | 33756 |
| 5 | Investigator site 1 - US0010017 | Miami | Florida | United States | 33173 |
| 6 | Investigator site 13 - US0010155 | West Lafayette | Indiana | United States | 47906 |
| 7 | Investigator site 5 - US0010088 | Buffalo | New York | United States | 14203 |
| 8 | Investigator site 4 - US0010137 | Fairborn | Ohio | United States | 45324 |
| 9 | Investigator site 25 - US0010158 | Pittsburgh | Pennsylvania | United States | 15213 |
| 10 | Investigator site 3 - US0010151 | Morgantown | West Virginia | United States | 26505 |
| 11 | Investigator site 14 - BG3590010 | Sofia | Bulgaria | 1431 | |
| 12 | Investigator site 15 - BG3590020 | Stara Zagora | Bulgaria | 6003 | |
| 13 | Investigator site 22 - HR3850003 | Split | Croatia | 21000 | |
| 14 | Investigator site 16 - HR3850002 | Zagreb | Croatia | 10000 | |
| 15 | Investigator site 11 - HU0360003 | Debrecen | Hungary | 4032 | |
| 16 | Investigator site 7 - HU0360008 | Pécs | Hungary | 7632 | |
| 17 | Investigator site 23 - IT0390006 | Roma | Italy | 00167 | |
| 18 | Investigator site 18 - PL0480048 | Wrocław | Poland | 50-220 | |
| 19 | Investigator site 19 - PL0480046 | Wrocław | Poland | 51-685 | |
| 20 | Investigator site 17 - PL0480047 | Łódź | Poland | 90-647 | |
| 21 | Investigator 24 - ES0340051 | Barcelona | Spain | 08003 | |
| 22 | Investigator site 8 - ES0340053 | Granada | Spain | 18016 | |
| 23 | Investigator site 12 - ES0340025 | Madrid | Spain | 28034 | |
| 24 | Investigator 20 - ES0340029 | Madrid | Spain | 28041 | |
| 25 | Investigator site 9 - ES0340052 | Sevilla | Spain | 41009 |
Sponsors and Collaborators
- argenx
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ARGX-113-2009