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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 (BALLAD)

A phase 2/3 study of efgartigimod PH20 SC in adult participants with bullous pemphigoid (BALLAD)

3

The study population (parts A and B pooled) was predominantly White (80.6%), female (73.5%), not Hispanic or Latino (99.0%), and located in the EU region or the UK (65 [66.3%]). The population was well balanced for the efgartigimod PH20 SC and placebo arms in age, sex at birth, weight, BMI, and ethnicity. Subgroup analyses of the primary and key secondary efficacy endpoints demonstrated that the demographic characteristics did not affect the interpretation of the efficacy results. In parts A and B pooled, more participants had newly diagnosed than relapsing BP (57 [58.2%] versus 41 [41.8%] participants, respectively) at baseline. Of all participants (parts A and B pooled), 59 (60.2%) had moderate BP at baseline and 39 (39.8%) had severe BP.

A total of 166 participants were screened and 98 were randomized 1:1 to receive efgartigimod PH20 SC (N=20 in part A, N=30 in part B) or placebo (N=20 in part A, N=28 in part B). Approximately 42% of all participants completed treatment (22 [44.0%] and 19 [39.6%] participants in the efgartigimod PH20 SC and placebo arms, respectively). The most common reason for treatment discontinuation was lack of efficacy in all participants in parts A and B pooled (30 [30.6%] participants). Approximately 71% of all participants completed the study (35 [70.0%] and 35 [72.9%] participants in the efgartigimod PH20 SC and placebo arms, respectively). The most common reason for early study discontinuation was withdrawal of consent in all participants (9 [9.2%] participants). Approximately 65% of all participants rolled over to the open-label extension (OLE) study, ARGX-113-2010 (31 [62.0%] and 33 [68.8%] participants in the efgartigimod PH20 SC and placebo arms, respectively). The number of patients or subjects at each stage of the study are as follows: - The number of eligible patients projected before the study initiation: 12 (Japan), 160 (overall) - The number of patients who underwent screening for eligibility: 5 (Japan), 166 (overall) - The number of subjects enrolled in the study: 3 (Japan), 98 (overall) - The number of subjects who completed this study and rolled over to the subsequent ARGX-113-2010 study: 1 (Japan), 64 (overall) - The number of subjects included in the analysis set: 3 (Japan), 98 (overall)

When considering adverse event (AE) frequencies and event rates, there was no clinically meaningful difference between the efgartigimod PH20 SC and placebo arms in the occurrence of serious adverse events (SAEs), grade >=3 AEs, adverse events of special interest (AESIs), or AEs leading to investigational medicinal product (IMP) discontinuation. Overall, there was <5% difference in the percentage of participants in each arm with AEs, SAEs, SAEs considered related to IMP or prednisone by the investigator, grade >=3 AEs considered related to IMP by the investigator, AEs leading to permanent or temporary IMP discontinuation, AESIs, or fatal AEs. There were no injection-related reaction SAEs. Fatal AEs occurred in 3 participants; 1 in the placebo arm and none in the efgartigimod PH20 SC arm were considered related to IMP by the investigator. A higher percentage of participants (>=5% difference between arms) in the efgartigimod PH20 SC arm than the placebo arm had AEs or AESIs considered IMP-related by the investigator or AEs considered procedure-related by the investigator. Grade >=3 AEs occurred in a higher percentage of participants in the placebo arm than the efgartigimod PH20 SC arm.

The primary endpoint was not met. There was no statistically significant difference between the efgartigimod PH20 SC and placebo arms for the primary endpoint in part B. In part A and parts A and B pooled, the proportion of participants with CRoff (complete remission while not receiving OCS for >=8 weeks) while receiving efgartigimod PH20 SC or placebo at week 36 was numerically higher (>=10% difference) in the efgartigimod PH20 SC arm than the placebo arm, but the difference was not meaningful. There was no meaningful difference between the efgartigimod PH20 and placebo arms in the normalized cumulative OCS dose (NCOD) from baseline to week 36 in parts A and B and in parts A and B pooled.

The primary endpoint was not met. No statistically significant difference was found between efgartigimod PH20 SC and placebo in the proportion of BP participants achieving CR without OCS for >=8 weeks at week 36 in part B. Efgartigimod PH20 SC was well tolerated with a consistent safety profile. Total IgG decreased rapidly and remained low.

June. 11, 2025

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2011220047

Ujiie Hideyuki

Hokkaido University Hospital

Kita14, Nishi5, Kita-Ku, Sapporo-shi, Hokkaido

Sayaka.Kakoi@thermofisher.com

Yamaji Hideomi

PPD-SNBL K.K.

St. Luke's tower 12 F, 8-1, Akashi-cho, Chuo-ku, Tokyo

+81-90-6106-5298

Hideomi.Yamaji@thermofisher.com

Complete

Mar. 26, 2023

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

*The participant is willing and able to do the following:

a. understand the requirements of the study
b. provide written informed consent
c. 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 by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and:
a) 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.

b) Female participants:
- 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.

- 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.

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 or chronic 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

*Use of an investigational product within 3 months before the first dose of IMP

*Previously participated in a clinical study with efgartigimod

*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

*Pregnant or lactating females and those who intend to become pregnant during the study

Bullous pemphigoid(BP)

ARGX-113 PH20 SC will be administered by subcutaneous injection on day 1 (baseline; week 0) and day 8 (week 1) at a dose of 2000 mg (via 2 separate 1000 mg injections), followed by weekly injections of ARGX-113 PH20 SC 1000 mg from week 2 through week 36 of the treatment period.

D010391

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.

+81-11-706-7061

Aug. 16, 2022

Bulgaria/Croatia/France/Germany/Greece/Hungary/Italy/Netherlands/Poland/Spain/UK/Serbia/Israel/USA/China/Australia/Latvia/Romania/Slovakia/Czech Republic