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

argenx98 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Bullous Pemphigoid

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Number of Participants With CRoff at Week 36

CRoff = complete remission while receiving efgartigimod PH20 SC or placebo and being off oral corticosteroid therapy for at least 8 weeks. Complete remission is defined as the absence of new lesions, complete healing of existing lesions and absence of pruritus.

Time frame: at week 36

Secondary Outcomes

Cumulative OCS Dose

OCS = oral corticosteroid

Time frame: up to week 36

Number of Participants Who Achieve an IGA-BP Score of 0 While Off OCS Therapy for ≥8 Weeks at Week 36

IGA-BP = Investigator Global Assessment of Bullous Pemphigoid. IGA-BP scores range from 0-4, with a higher score representing severe BP. OCS = oral corticosteroid

Time frame: at week 36

Number of Participants With CDA Who Remained Free of Relapse Through Week 36

Control of disease activity (CDA) is defined as the point at which new lesions ceased to form, established lesions began to heal, and pruritic symptoms started to abate. Relapse is defined as the appearance of 3 or more new lesions a month or at least 1 large lesion that did not heal within 1 week, or extension of established lesions or daily pruritus in a participant who had achieved CDA.

Time frame: up to week 36

Number of Participants With CRmin at Week 36

CRmin = complete remission receiving minimal oral corticosteroids for at least 8 weeks. Minimal oral corticosteroid (OCS) therapy is defined as ≤0.1 mg/kg/day of prednisone (or equivalent).

Time frame: at week 36

Change From Baseline to Week 36 in the 24-Hour Average Itch NRS Score

Itch NRS = Itch Numerical Rating Scale. The Itch NRS scores range from 0-10 with 10 representing the worst imaginable itch.

Time frame: up to week 36

Changes From Baseline in the BPDAI Total Activity Score

BPDAI = Bullous Pemphigoid Disease Area Index (BPDAI) Total Activity Score is a tool to objectively measure disease activity. BPDAI scores range from 0 to 360 with a higher score indicating more severe disease (max 240 for total skin activity and 120 for mucosal activity).

Time frame: up to week 36

Time to CDA

CDA = control of disease activity, the point at which new lesions ceased to form, established lesions began to heal, and pruritic symptoms started to abate.

Time frame: up to week 36

Time to CR

CR = complete remission, the absence of new lesions, complete healing of existing lesions, and absence of pruritus.

Time frame: up to week 36

Time to CRmin

CRmin = complete remission, the absence of new lesions, complete healing of existing lesions, and absence of pruritus while being on minimal dose of OCS for ≥8 Weeks. OCS = oral corticosteroid. Minimal OCS therapy is defined as an oral prednisone dosage of ≤0.10 mg/kg/day (or equivalent).

Time frame: up to week 36

Time to CRoff/PRoff

CRoff= complete remission (the absence of new lesions, complete healing of existing lesions, and absence of pruritus) while receiving efgartigimod PH20 SC or placebo and being off oral corticosteroid therapy for at least 8 weeks. PRoff = partial remission (the presence of only new transient lesions) while receiving efgartigimod PH20 SC or placebo and being off oral corticosteroid therapy for at least 8 weeks.

Time frame: up to week 36

Time to CRoff

CRoff is defined as the absence of new lesions, complete healing of existing lesions, and absence of pruritus while being off OCS therapy for ≥8 weeks.

Time frame: up to week 36

Time From CDA to Achieve Relapse

CDA is defined as the point at which new lesions ceased to form, established lesions began to heal, and pruritic symptoms started to abate. Relapse is defined as the appearance of 3 or more new lesions a month or at least 1 large lesion that did not heal within 1 week, or extension of established lesions or daily pruritus in a participant who had achieved CDA.

Time frame: up to week 36

Number of Participants Who Receive Rescue Therapy Before Week 36

Time frame: at week 36

The AIS From the GTI

The Aggregate Improvement Score (AIS) from the Glucocorticoid Toxicity Index (GTI) can range from -346 to 439 with a higher score representing greater corticosteroid toxicity. If a study drug is effective at lowering greater corticosteroid toxicity over time, the score will be lower.

Time frame: up to week 36

The CWS From the GTI

The Cumulative Worsening Score (CWS) from the Glucocorticoid Toxicity Index (GTI) can range from 0 to 439 with a higher score representing greater corticosteroid toxicity.

Time frame: up to week 36

EQ-5D-5L VAS Scores Over Time

The EuroQol 5-Dimension 5-Level Visual Analog Scale (EQ-5D-5L VAS) scores range from 0-100 with 0 representing the worst health.

Time frame: up to week 36

DLQI Scores Over Time

Dermatology Life Quality Index (DLQI) assess the participant's perception of the impact of skin diseases on different aspects of their health-related QoL. Scores range from 0 to 30 with a higher score representing a worse quality of life.

Time frame: up to week 36

ABQoL Scores Over Time

Autoimmune Bullous Disease Quality of Life Index (ABQoL) questionnaire assesses the impact of Autoimmune Bullous Disease and their therapies on the daily life of patients. Scores range from 0 to 51 with a higher score representing a worse quality of life.

Time frame: up to week 36

Efgartigimod Serum Concentrations

Time frame: up to week 36

Percent Change of Total IgG Serum Levels From Baseline Over Time

Time frame: up to 36 weeks

Percent Change of Anti-BP180 and Anti-BP230 Antibodies From Baseline Over Time

Time frame: up to 36 weeks

Incidence of Antidrug Antibodies Against Efgartigimod and Antibodies Produced Against rHuPH20

Time frame: up to 46 weeks

Number of Participants (or Their Caregivers) Who Are Determined by Site Staff to be Sufficiently Competent in (Self-)Administering Efgartigimod PH20 SC

Time frame: up to week 32

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

Overview

Conditions

Interventions

Eligibility

Locations (129)

Outcomes

Primary Outcomes

Secondary Outcomes