A Study to Assess the Efficacy and Safety of a Subcutaneous Formulation of Efgartigimod PH20 SC in Adults With Pemphigus (Vulgaris or Foliaceus)

NCT ID: NCT04598451

Last Updated: 2024-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 222 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-01
• Study Completion Date: 2023-08-22

Brief Summary

This is a prospective, multicenter, randomized, double-blinded, placebo-controlled trial to investigate the efficacy, safety, patient outcome measures, tolerability, immunogenicity, PK, and PD of efgartigimod PH20 SC in adult participants aged from 18 years with PV or PF. The trial comprises a screening period of up to 3 weeks, a treatment period of up to 30 weeks, and an 8-week follow-up period for participants who do not enroll into the open-label extension (OLE) trial ARGX-113-1905. The primary objective of the ARGX-113-1904 trial is to demonstrate the efficacy of subcutaneous administration of efgartigimod co-formulated with recombinant human hyaluronidase PH20 (Efgartigimod PH20 SC) compared to placebo in the treatment of participants with Pemphigus Vulgaris (PV). Secondary objectives are to also demonstrate the efficacy of efgartigimod PH20 SC in the treatment of participants with Pemphigus Foliaceus (PF), and to demonstrate early onset of action and a prednisone-sparing effect. After confirmation of eligibility, participants will be randomized in a 2: 1 ratio to receive efgartigimod PH20 SC or placebo

Conditions

Pemphigus Vulgaris; Pemphigus Foliaceus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

efgartigimod PH20 SC

patients receiving efgartigimod PH20 SC on top of prednisone

Group Type: EXPERIMENTAL

efgartigimod PH20 SC

Intervention Type: BIOLOGICAL

Subcutaneous injection of efgartigimod using rHuPH20 (PH20) as a permeation enhancer

prednisone

Intervention Type: DRUG

Oral prednisone tablets

placebo

patients receiving placebo on top of prednisone

Group Type: EXPERIMENTAL

Placebo

Intervention Type: OTHER

Subcutaneous injection of placebo

prednisone

Intervention Type: DRUG

Oral prednisone tablets

Interventions

efgartigimod PH20 SC

Subcutaneous injection of efgartigimod using rHuPH20 (PH20) as a permeation enhancer

Intervention Type: BIOLOGICAL

Placebo

Subcutaneous injection of placebo

Intervention Type: OTHER

prednisone

Oral prednisone tablets

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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 18 years at the time of signing the informed consent form (ICF).

3. The participant has a clinical diagnosis of PV (mucosal, cutaneous, mucocutaneous) or PF which has been confirmed by cutaneous histology, positive direct immunofluorescence (IF), and positive indirect IF and/or enzyme-linked immunosorbent assay (ELISA).

4. The participant meets one of the following profiles:

1. Newly diagnosed disease with PDAI ≥15 at baseline and naïve to treatment

2. Newly diagnosed disease with PDAI ≥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.

3. Experiencing flare with PDAI ≥15, a maximum of 4 years since diagnosis, and off prednisone therapy ± a conventional immunosuppressant (e.g., azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) or dapsone. Note: conventional immunosuppressants and dapsone must be discontinued before baseline.

4. Experiencing flare with PDAI ≥15, a maximum of 4 years since diagnosis, and receiving a tapered dose of oral prednisone (or the equivalent), provided that prednisone has been given at stable dose ± a conventional immunosuppressant for at least 2 weeks and patients are fit to start prednisone treatment at 0.5 mg/kg qd at baseline.

5. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating clinical trials and:

1. 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.

2. 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 method, which should be maintained at minimum until after the last dose of IMP

6. For Japanese participants enrolled in sites in Japan only: A Japanese participant is defined as a participant whose parents and 4 grandparents are Japanese, and who has Japanese nationality, was born in Japan, has not lived outside of Japan for a total of >10 years, and currently lives in Japan.

Exclusion Criteria

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 <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 patient 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 or conventional immunosuppressants (e.g., 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, dapsone, sulfasalazine, tetracyclines, nicotinamide at doses above the recommended daily allowance (RDA)/dietary reference intake (DRI), plasmapheresis/ plasma exchange, immunoadsorption, and IVIg.

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:

• 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

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 patient at undue risk.

11. Pregnant and lactating women and those intending to become pregnant during the trial.

12. Current or history (i.e. 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 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: Hepatitis B Virus, Hepatitis C Virus , HIV.

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 one 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

argenx

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Investigator site 77 - US0010086

Birmingham, Alabama, United States

Investigator site 97 - US0010091

Scottsdale, Arizona, United States

Investigator site 121 - US0010092

Redwood City, California, United States

Investigator site 125 - US0010153

Castle Rock, Colorado, United States

Investigator site 2 - US0010087

Boca Raton, Florida, United States

Investigator site 99 - US0010117

Miami, Florida, United States

Investigator site 78 - US0010109

Orlando, Florida, United States

Investigator site 127 - US0010155

West Lafayette, Indiana, United States

Investigator site 61 - US0010090

Minneapolis, Minnesota, United States

Investigator site 102 - US0010098

St Louis, Missouri, United States

Investigator site 19 - US0010088

Buffalo, New York, United States

Investigator site 136 - US0010196

New York, New York, United States

Investigator site 60 - US0010096

Durham, North Carolina, United States

Investigator site 20 - US0010094

Cleveland, Ohio, United States

Investigator site 73 - US00100

Philadelphia, Pennsylvania, United States

Investigator site 101 - US0010097

Philadelphia, Pennsylvania, United States

Investigator site 98 - US0010107

Dallas, Texas, United States

Investigator site 1 - US0010084

Dripping Springs, Texas, United States

Investigator site 126 - US0010182

Houston, Texas, United States

Investigator site 88 - US0010114

Houston, Texas, United States

Investigator site 59 - US0010106

Norfolk, Virginia, United States

Investigator site 24 - AU0610006

Sydney, New South Wales, Australia

Investigator site 5 - AU0610007

Parkville, Victoria, Australia

Investigator site 103 - AU0610013

Melbourne, , Australia

Investigator site 30 - BG350012

Pleven, , Bulgaria

Investigator site 31 - BG3590013

Plovdiv, , Bulgaria

Investigator site 4 - BG3590010

Sofia, , Bulgaria

Investigator site 2 - BG3590009

Sofia, , Bulgaria

Investigator site 13 - BG3590011

Sofia, , Bulgaria

Investigator site 110 - CN0860017

Beijing, , China

Investigator site 111 - CN0860018

Chendu, , China

Investigator site 131 - CH0860027

Chongqing, , China

Investigator site 118 - CN0860023

Fujian, , China

Investigator site 120 - CN0860022

Guangzhou, , China

Investigator site 128 - CH0860053

Guangzhou, , China

Investigator site 109 - CN0860021

Guanzhou, , China

Investigator site 119 - CN0860024

Nanjing, , China

Investigator site 112 - CN0860020

Shanghai, , China

Investigator site 108 - CN0860016

Shanghai, , China

Investigator site 113 - CN0860025

Wuhan, , China

Investigator site 123 - CN0860019

Wuhan, , China

Investigator site 129 - CH0860026

Zhengzhou, , China

Investigator site 34 - FR0330028

Bobigny, , France

Investigator site 33 - FR0330027

La Tronche, , France

Investigator site 46 - FR0330029

Rouen, , France

Investigator site 32 - FR0330026

Saint-Etienne, , France

Investigator site 63 - GE9950014

Tbilisi, , Georgia

Investigator site 132 - GE9950030

Tbilisi, , Georgia

Investigator site 35 - GE9950013

Tbilisi, , Georgia

Investigator site 36 - GE9950015

Tbilisi, , Georgia

Investigator site 64 - DE0490029

Berlin, , Germany

Investigator site 48 - DE0490030

Dresden, , Germany

Investigator site 49 - DE0490024

Frankfurt am Main, , Germany

Investigator site 47 - DE0490023

Freiburg im Breisgau, , Germany

Investigator site 38 - DE0490028

Kiel, , Germany

Investigator site 37 - DE0490002

Lübeck, , Germany

Investigator site 68 - DE0490001

Marburg, , Germany

Investigator site 25 - DE0490025

Tübingen, , Germany

Investigator site 79 - DE0490027

Ulm, , Germany

Investigator site 21 - DE0490026

Würzburg, , Germany

Investigator site 40 - GR0300004

Athens, , Greece

Investigator site 51 - GR0300006

Athens, , Greece

Investigator site 69 - GR0300001

Athens, , Greece

Investigator site 39 - GR0300003

Chaïdári, , Greece

Investigator site 50 - GR0300002

Thessaloniki, , Greece

Investigator site 41 - GR0300005

Thessaloniki, , Greece

Investigator site 133 - HU0360023

Budapest, , Hungary

Investigator site 22 - HU0360003

Debrecen, , Hungary

Investigator site 14 - HU0360001

Pécs, , Hungary

Investigator site 42 - HU0360002

Szeged, , Hungary

Investigator site 80 - IN0910002

Ahmedabad, , India

Investigator site 100 - IN0910001

Chandigarh, , India

Investigator site 90 - IN0910004

Lucknow, , India

Investigator site 91 - IN0910003

Nagpur, , India

Investigator site 12 - ISR9720002

Tel Aviv, , Israel

Investigator site 11 - IT0390006

Rome, Lazio, Italy

Investigator site 104 - IT0390039

Catania, , Italy

Investigator site 52 - IT0390031

Florence, , Italy

Investigator site 92 - IT0390030

Genova, , Italy

Investigator site 70 - IT0390038

Perugia, , Italy

Investigator site 43 - IT390005

Roma, , Italy

Investigator site 71 - IT0390040

Siena, , Italy

Investigator site 94 - JP0810046

Aichi, , Japan

Investigator site 81 - JP0810040

Hiroshima, , Japan

Investigator site 82 - JP0810042

Kofu, , Japan

Investigator site 85 - JP0810050

Kurume, , Japan

Investigator site 84 - JP0810047

Okayama, , Japan

Investigator site 93 - JP0810041

Okayama, , Japan

Investigator site 86 - JP0810049

Osaka, , Japan

Investigator site 74 - JP0810045

Sapporo, , Japan

Investigator site 124 - JP0810067

Sendai, , Japan

Investigator site 83 - JP0810043

Tokyo, , Japan

Investigator site 26 - PL0480027

Katowice, , Poland

Investigator site 72 - PL0480032

Lodz, , Poland

Investigator site 95 - PL0480036

Poznan, , Poland

Investigator site 27 - PL0480025

Rzeszów, , Poland

Investigator site 28 - PL0480028

Wroclaw, , Poland

Investigator site 106 - RO0400013

Bucharest, , Romania

Investigator site 105 - RO0400014

Cluj-Napoca, , Romania

Investigator site 107 - RO0400015

Iași, , Romania

Investigator site 54 - RU0070035

Chelyabinsk, , Russia

Investigator site 57 - RU0070029

Kazan', , Russia

Investigator site 55 - RU0070030

Krasnodar, , Russia

Investigator site 53 - RU0070032

Rostov-on-Don, , Russia

Investigator site 56 - RU0070031

Saint Petersburg, , Russia

Investigator site 65 - RU0070034

Saint Petersburg, , Russia

Investigator site 66 - RU0070028

Saratov, , Russia

Investigator site 58 - RU0070033

Yekaterinburg, , Russia

Investigator site 116 - RS3810011

Belgrade, , Serbia

Investigator site 122 - RS3810010

Belgrade, , Serbia

Investigator site 115 - RS3810012

Niš, , Serbia

Investigator site 114 - RS3810009

Novi Sad, , Serbia

Investigator site 29 - ES0340026

Barcelona, , Spain

Investigator site 15 - ES0340032

Barcelona, , Spain

Investigator site 130 - ES0340053

Granada, , Spain

Investigator site 67 - ES0340034

Madrid, , Spain

Investigator site 10 - ES0340025

Madrid, , Spain

Invetistigator site 8 - ES0340029

Madrid, , Spain

Investigator site 6 - ES0340027

Madrid, , Spain

Investigator site 134 - ES0340057

Málaga, , Spain

Investigator site 23 - ES0340031

Pamplona, , Spain

Investigator site 7 - ES0340028

Seville, , Spain

Investigator site 76 - TR0900020

Gaziantep, , Turkey (Türkiye)

Investigator site 75 - TR0900012

Istanbul, , Turkey (Türkiye)

Investigator site 87 - TR0900011

Istanbul, , Turkey (Türkiye)

Investigator site 89 - UA3800017

Dnipro, , Ukraine

Investigator site 45 - UA3800023

Ivano-Frankivsk, , Ukraine

Investigator site 16 - UA3800020

Kyiv, , Ukraine

Investigator site 18 - UA3800019

Kyiv, , Ukraine

Investigator site 62 - UA3800021

Lviv, , Ukraine

Investigator site 17 - UA3800018

Zaporizhzhia, , Ukraine

Investigator site 117 - UK0440021

Birmingham, , United Kingdom

Investigator site 96 - UK0440022

Bristol, , United Kingdom

Investigator site 135 - GB0440037

Southampton, , United Kingdom

Countries

United States; Australia; Bulgaria; China; France; Georgia; Germany; Greece; Hungary; India; Israel; Italy; Japan; Poland; Romania; Russia; Serbia; Spain; Turkey (Türkiye); Ukraine; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ARGX-113-1904

Identifier Type: -

Identifier Source: org_study_id