A Randomized, Double-Blinded, Placebo-Controlled Trial of Efgartigimod PH20 SC in Adult Patients With Pemphigus (Vulgaris or Foliaceus)

JRCT ID: jRCT2061210025

Registered date:16/07/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Adult patients with moderate to severe pemphigus vulgaris (PV) or pemphigus foliaceus (PF)
• Date of first enrollment: 16/04/2021
• Target sample size: 12
• Countries of recruitment: Bulgaria,Japan,France,Japan,Germany,Japan,Greece,Japan,Hungary,Japan,Italy,Japan,Poland,Japan,Spain,Japan,Romania,Japan,USA,Japan,UK,Japan,Australia,Japan,Georgia,Japan,India,Japan,Israel,Japan,Russia,Japan,Serbia,Japan,Turkey,Japan,Ukraine,Japan,Netherlands,Japan
• Study type: Interventional
• Intervention(s): Efgartigimod PH20 SC will be administered by subcutaneous (SC) injection on day 1 and day 8 at a dose of 2000 mg, followed by weekly SC administrations of 1000 mg until complete remission on minimal therapy (CRmin) is observed.

Outcome(s)

• Primary Outcome: Proportion of PV participants who achieve CRmin (complete remission on minimal therapy) within 30 weeks

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Participants are eligible to be included in the trial only if all of the following criteria apply:
1. Ability to understand the requirements of the trial, to provide written informed consent (including consent for the use and disclosure of research-related health information), willingness and ability to comply with the trial protocol procedures (including required trial visits).
2. The participant is male or female, and aged from 20 years at the time of signing the informed consent form (ICF).
3. For Japanese participants enrolled in sites in Japan only: A Japanese participant is defined as a participant whose parents and 4 grandparents are Japanese, who has the Japanese nationality, was born in Japan, has not lived outside of Japan for a total of >10 years, and currently lives in Japan.
4. The participant has a clinical diagnosis of PV (mucosal, cutaneous, mucocutaneous) or PF that has been confirmed by cutaneous histology, positive direct immunofluorescence (IF), and positive indirect IF and/or ELISA.
5. The participant meets 1 of the following profiles:
a. Newly diagnosed disease with PDAI activity score >=15 at baseline and naive to treatment.
b. Newly diagnosed disease with PDAI activity score >=15 while receiving a first course
of oral prednisone (or equivalent). According to clinical judgment, the participant has shown no significant improvement of PV or PF signs for at least 2 weeks before baseline and is considered fit to start prednisone treatment at 0.5 mg/kg qd at baseline.
c. Experiencing flare with PDAI activity score >=15, a maximum of 4 years since disease onset, and off prednisone therapy +- a conventional immunosuppressant (eg, azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) or dapsone.
Note: conventional immunosuppressants and dapsone must be discontinued before baseline.
d. Experiencing flare with PDAI activity score >=15, a maximum of 4 years since disease onset, and receiving a tapered dose of oral prednisone (or equivalent), provided that prednisone has been given at stable dose +- a conventional immunosuppressant (eg, azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) or dapsone for at least 2 weeks and participants are fit to start prednisone treatment at 0.5 mg/kg qd at baseline. Note: conventional immunosuppressants and dapsone must be discontinued before baseline.
6. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating clinical trials and:
a. Male participants:
- Male participants must agree to use acceptable method of contraception, and not donate sperm from signing the ICF until the end of the study.
b. Female participants:
- Women of childbearing potential must:
- have a negative serum pregnancy test at screening and negative urine pregnancy test at baseline before the IMP can be administered.
- agree to use a highly effective or acceptable contraception methods, which should be maintained at minimum until 90 days after the last dose of IMP.

Exclude criteria

Participants are excluded from the trial if any of the following criteria apply:
1. Participant has a confirmed diagnosis of paraneoplastic pemphigus, drug-induced pemphigus, pemphigus vegetans, pemphigus erythematosus, or any other non-PV/non-PF autoimmune blistering disease.
2. Participants with mild disease severity as defined by PDAI activity score <15 at baseline.
3. Participants who show a significant improvement of PV or PF in the period from screening to baseline according to clinical judgment (eg, the participant has achieved DC or a substantial reduction in PDAI activity score during screening period).
4. The participant has been administered therapy(ies) other than oral prednisone, conventional immunosuppressants (eg, azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) or dapsone within 2 months before the baseline visit and that can affect clinical disease activity. For example, excluded medications are intravenous methylprednisolone, sulfasalazine, tetracyclines, nicotinamide at doses above the recommended daily allowance (RDA)/dietary reference intake (DRI), plasmapheresis/plasma exchange, immunoadsorption, and IVIg. Note: conventional immunosuppressants and dapsone must be discontinued before baseline. Nicotinamide doses at or below RDA/DRI from oral supplements is allowed.
5. Use of any monoclonal antibody (including rituximab or another anti-CD20 biologic) within 6 months before the baseline visit.
6. Known hypersensitivity to any of the components of the administered treatments.
7. The participant has a known contraindication to oral prednisone.
8. The participant has a history of refractory disease, as defined by a failure to respond to first-line and second-line therapies.
9. Participants who have a history of malignancy unless deemed cured by adequate
treatment with no evidence of recurrence for >=3 years before first IMP administration. Participants with any of the following cancers can be included at any time, provided they are adequately treated prior to their participation in the study:
a. Basal cell or squamous cell skin cancer
b. Carcinoma in situ of the cervix
c. Carcinoma in situ of the breast
d. Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
10. Participants with clinical evidence of other significant serious disease or participants who
recently underwent or have planned a major surgery during the period of the trial, or any other condition in the opinion of the investigator, that could confound the results of the trial or put the participant at undue risk.
11. Pregnant and lactating women and those intending to become pregnant during the trial or within 90 days after the last administration of IMP.
12. Current or history (ie, within 12 months of screening) of alcohol, drug, or medication abuse.
13. Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of PV or PF or put the participant at undue risk.
14. The participant has a Karnofsky performance score <60%.
15. Vaccination with live/attenuated viral vaccines within 28 days prior to randomization.
16. The participant has clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection.
17. Positive serum test at screening for an active viral infection with any of the following conditions:
a. Hepatitis B Virus (HBV) that is indicative of an acute or chronic infection.
b. Hepatitis C Virus (HCV) based on HCV antibody assay.
c. Human immunodeficiency virus (HIV) based on test results that are associated with an acquired immunodeficiency syndrome (AIDS)-defining condition or a CD4 count <200 cells/mm3).
18. The participant has total immunoglobulin G (IgG) <6 g/L at screening.
19. The participant has previously participated in a trial with efgartigimod and has received at least 1 administration of IMP.
20. Use of an investigational drug within 3 months or 5 half-lives of the drug (whichever is longer) prior to first IMP administration.

Related Information

• Primary Sponsor: Aoyama Yumi