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

Pemphigus Vulgaris Clinical Trial

— ADDRESS  

Official title:

A Randomized, Double-Blinded, Placebo-Controlled Trial to Investigate the Efficacy, Safety, and Tolerability of Efgartigimod PH20 SC in Adult Patients With Pemphigus (Vulgaris or Foliaceus)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04598451
• Other study ID #: ARGX-113-1904
• Status: Completed
• Phase: Phase 3
• Start date: December 1, 2020
• Est. completion date: August 22, 2023

Study information

• Verified date: September 2023
• Source: argenx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 222
• Est. completion date: August 22, 2023
• Est. primary completion date: August 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pemphigus
• Pemphigus Foliaceus
• Pemphigus Vulgaris

Intervention

Biological:
• efgartigimod PH20 SC
Subcutaneous injection of efgartigimod using rHuPH20 (PH20) as a permeation enhancer

Other:
• Placebo
Subcutaneous injection of placebo

Drug:
• prednisone
Oral prednisone tablets

Locations

Country	Name	City	State
Australia	Investigator site 103 - AU0610013	Melbourne
Australia	Investigator site 5 - AU0610007	Parkville	Victoria
Australia	Investigator site 24 - AU0610006	Sydney	New South Wales
Bulgaria	Investigator site 30 - BG350012	Pleven
Bulgaria	Investigator site 31 - BG3590013	Plovdiv
Bulgaria	Investigator site 13 - BG3590011	Sofia
Bulgaria	Investigator site 2 - BG3590009	Sofia
Bulgaria	Investigator site 4 - BG3590010	Sofia
China	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 108 - CN0860016	Shanghai
China	Investigator site 112 - CN0860020	Shanghai
China	Investigator site 113 - CN0860025	Wuhan
China	Investigator site 123 - CN0860019	Wuhan
China	Investigator site 129 - CH0860026	Zhengzhou
France	Investigator site 34 - FR0330028	Bobigny
France	Investigator site 33 - FR0330027	La Tronche
France	Investigator site 46 - FR0330029	Rouen
France	Investigator site 32 - FR0330026	Saint-Étienne
Georgia	Investigator site 132 - GE9950030	Tbilisi
Georgia	Investigator site 35 - GE9950013	Tbilisi
Georgia	Investigator site 36 - GE9950015	Tbilisi
Georgia	Investigator site 63 - GE9950014	Tbilisi
Germany	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
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
Greece	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 41 - GR0300005	Thessaloníki
Greece	Investigator site 50 - GR0300002	Thessaloníki
Hungary	Investigator site 133 - HU0360023	Budapest
Hungary	Investigator site 22 - HU0360003	Debrecen
Hungary	Investigator site 14 - HU0360001	Pécs
Hungary	Investigator site 42 - HU0360002	Szeged
India	Investigator site 80 - IN0910002	Ahmedabad
India	Investigator site 100 - IN0910001	Chandigarh
India	Investigator site 90 - IN0910004	Lucknow
India	Investigator site 91 - IN0910003	Nagpur
Israel	Investigator site 12 - ISR9720002	Tel Aviv
Italy	Investigator site 104 - IT0390039	Catania
Italy	Investigator site 52 - IT0390031	Firenze
Italy	Investigator site 92 - IT0390030	Genova
Italy	Investigator site 70 - IT0390038	Perugia
Italy	Investigator site 11 - IT0390006	Roma	Lazio
Italy	Investigator site 43 - IT390005	Roma
Italy	Investigator site 71 - IT0390040	Siena
Japan	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
Poland	Investigator site 26 - PL0480027	Katowice
Poland	Investigator site 72 - PL0480032	Lódz
Poland	Investigator site 95 - PL0480036	Poznan
Poland	Investigator site 27 - PL0480025	Rzeszów
Poland	Investigator site 28 - PL0480028	Wroclaw
Romania	Investigator site 106 - RO0400013	Bucharest
Romania	Investigator site 105 - RO0400014	Cluj-Napoca
Romania	Investigator site 107 - RO0400015	Iasi
Russian Federation	Investigator site 54 - RU0070035	Chelyabinsk
Russian Federation	Investigator site 58 - RU0070033	Ekaterinburg
Russian Federation	Investigator site 57 - RU0070029	Kazan
Russian Federation	Investigator site 55 - RU0070030	Krasnodar
Russian Federation	Investigator site 53 - RU0070032	Rostov-on-Don
Russian Federation	Investigator site 56 - RU0070031	Saint Petersburg
Russian Federation	Investigator site 65 - RU0070034	Saint Petersburg
Russian Federation	Investigator site 66 - RU0070028	Saratov
Serbia	Investigator site 116 - RS3810011	Belgrad
Serbia	Investigator site 122 - RS3810010	Belgrade
Serbia	Investigator site 115 - RS3810012	Niš
Serbia	Investigator site 114 - RS3810009	Novi Sad
Spain	Investigator site 15 - ES0340032	Barcelona
Spain	Investigator site 29 - ES0340026	Barcelona
Spain	Investigator site 130 - ES0340053	Granada
Spain	Investigator site 10 - ES0340025	Madrid
Spain	Investigator site 6 - ES0340027	Madrid
Spain	Investigator site 67 - ES0340034	Madrid
Spain	Invetistigator site 8 - ES0340029	Madrid
Spain	Investigator site 134 - ES0340057	Málaga
Spain	Investigator site 23 - ES0340031	Pamplona
Spain	Investigator site 7 - ES0340028	Sevilla
Turkey	Investigator site 76 - TR0900020	Gaziantep
Turkey	Investigator site 75 - TR0900012	Istanbul
Turkey	Investigator site 87 - TR0900011	Istanbul
Ukraine	Investigator site 89 - UA3800017	Dnipro
Ukraine	Investigator site 45 - UA3800023	Ivano-Frankivs'k
Ukraine	Investigator site 16 - UA3800020	Kyiv
Ukraine	Investigator site 18 - UA3800019	Kyiv
Ukraine	Investigator site 62 - UA3800021	Lviv
Ukraine	Investigator site 17 - UA3800018	Zaporizhzhia
United Kingdom	Investigator site 117 - UK0440021	Birmingham
United Kingdom	Investigator site 96 - UK0440022	Bristol
United Kingdom	Investigator site 135 - GB0440037	Southampton
United States	Investigator site 77 - US0010086	Birmingham	Alabama
United States	Investigator site 2 - US0010087	Boca Raton	Florida
United States	Investigator site 19 - US0010088	Buffalo	New York
United States	Investigator site 125 - US0010153	Castle Rock	Colorado
United States	Investigator site 20 - US0010094	Cleveland	Ohio
United States	Investigator site 98 - US0010107	Dallas	Texas
United States	Investigator site 1 - US0010084	Dripping Springs	Texas
United States	Investigator site 60 - US0010096	Durham	North Carolina
United States	Investigator site 126 - US0010182	Houston	Texas
United States	Investigator site 88 - US0010114	Houston	Texas
United States	Investigator site 99 - US0010117	Miami	Florida
United States	Investigator site 61 - US0010090	Minneapolis	Minnesota
United States	Investigator site 136 - US0010196	New York	New York
United States	Investigator site 59 - US0010106	Norfolk	Virginia
United States	Investigator site 78 - US0010109	Orlando	Florida
United States	Investigator site 101 - US0010097	Philadelphia	Pennsylvania
United States	Investigator site 73 - US00100	Philadelphia	Pennsylvania
United States	Investigator site 121 - US0010092	Redwood City	California
United States	Investigator site 102 - US0010098	Saint Louis	Missouri
United States	Investigator site 97 - US0010091	Scottsdale	Arizona
United States	Investigator site 127 - US0010155	West Lafayette	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
argenx

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  China,  France,  Georgia,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Japan,  Poland,  Romania,  Russian Federation,  Serbia,  Spain,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Pemphigus Vulgaris (PV) participants who achieve complete clinical remission (CR) on minimal Prednisone therapy	Proportion of Pemphigus Vulgaris participants who achieve Clinical Remission on minimal Prednisone therapy	30 weeks treatment period
Secondary	Proportion of Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF) participants who achieve complete clinical remission (CR) on minimal Prednisone therapy	Proportion of Pemphigus Vulgaris and Pemphigus Foliaceus participants who achieve complete clinical remission on minimal Prednisone therapy	30 weeks treatment period
Secondary	Cumulative prednisone dose over the trial in Pemphigus Vulgaris participants	Cumulative prednisone dose over the trial in Pemphigus Vulgaris participants	Up to 30 weeks
Secondary	Time to complete clinical remission in Pemphigus Vulgaris participants	Time to complete clinical remission in Pemphigus Vulgaris participants	Up to 30 weeks
Secondary	Time to Disease Control (DC) in Pemphigus Vulgaris (PV) participants	Time to Disease Control in Pemphigus Vulgaris participants	Up to 30 weeks
Secondary	Proportion of Pemphigus Foliaceus (PF) participants who achieve complete clinical remission (CR) on minimal prednisone therapy	Proportion of Pemphigus Foliaceus (PF) participants who achieve complete clinical remission (CR) on minimal prednisone therapy	30 weeks treatment period
Secondary	Cumulative prednisone dose over the trial in Pemphigus Vulgaris and Pemphigus Foliaceus participants	Cumulative prednisone dose over the trial in Pemphigus Vulgaris and Pemphigus Foliaceus participants	Up to 30 weeks
Secondary	Time to complete clinical remission in Pemphigus Vulgaris and Pemphigus Foliaceus participants	Time to complete clinical remission in Pemphigus Vulgaris and Pemphigus Foliaceus participants	Up to 30 weeks
Secondary	Time to disease control in Pemphigus Vulgaris and Pemphigus Foliaceus participants	Time to disease control in Pemphigus Vulgaris and Pemphigus Foliaceus participants	Up to 30 weeks
Secondary	Rate of treatment failure	Rate of treatment failure	Up to 30 weeks
Secondary	Rate of flare	Rate of flare	Up to 30 weeks
Secondary	Pemphigus Disease Area Index at each visit	Pemphigus Disease Area Index at each visit	Up to 41 weeks
Secondary	Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE)	Incidence of Treatment-Emergent Adverse Events, Adverse Events of Special Interest, and Serious Adverse Events	Up to 41 weeks
Secondary	Severity of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE)	Severity of Treatment-Emergent Adverse Events, Adverse Events of Special Interest, and Serious Adverse Events	Up to 41 weeks
Secondary	Composite Glucocorticoid Toxicity Index (C-GTI) comprising the Aggregate Improvement Score (AIS) and the Cumulative Worsening Score (CWS)	Composite Glucocorticoid Toxicity Index comprising the Aggregate Improvement Score and the Cumulative Worsening Score	Up to 30 weeks
Secondary	EuroQol Five-Dimension Five-Level Scale (EQ-5D-5L) score	EuroQol Five-Dimension Five-Level Scale score	30 weeks treatment period
Secondary	Autoimmune Bullous Disease Quality of Life (ABQOL) score	Autoimmune Bullous Disease Quality of Life score	30 weeks treatment period
Secondary	Efgartigimod serum concentrations	Efgartigimod serum concentrations	Up to 38 weeks
Secondary	Total immunoglobulin G and subtype (IgG1, IgG2, IgG3, IgG4) serum levels	Total immunoglobulin G and subtype (IgG1, IgG2, IgG3, IgG4) serum levels	Up to 41 weeks
Secondary	Anti desmoglein-1 and -3 autoantibodies serum levels	Anti desmoglein-1 and -3 autoantibodies serum levels	Up to 41 weeks
Secondary	Incidence of anti-drug antibodies (ADA) to efgartigimod PH20 SC	Incidence of anti-drug antibodies to efgartigimod PH20 SC	Up to 38 weeks
Secondary	Prevalence of anti-drug antibodies (ADA) to efgartigimod PH20 SC	Prevalence of anti-drug antibodies to efgartigimod PH20 SC	Up to 38 weeks
Secondary	Incidence of antibodies produced against recombinant human hyaluronidase (rHuPH20) (plasma levels)	Incidence of antibodies produced against recombinant human hyaluronidase (rHuPH20) (plasma levels)	Up to 31 weeks
Secondary	Prevalence of antibodies produced against recombinant human hyaluronidase (rHuPH20)	Prevalence of antibodies produced against recombinant human hyaluronidase (rHuPH20)	Up to 31 weeks
Secondary	Number of participants or caregivers completing the self-administration training	Number of participants or caregivers completing the self-administration training	Up to 41 weeks
Secondary	Percentage of participants or caregivers completing the self-administration training	Percentage of participants or caregivers completing the self-administration training	Up to 41 weeks
Secondary	Number of participants or caregivers determined by the site staff to be sufficiently competent to self-administer efgartigimod PH20 SC	Number of participants or caregivers determined by the site staff to be sufficiently competent to self-administer efgartigimod PH20 SC	Up to 41 weeks
Secondary	Percentage of participants or caregivers determined by the site staff to be sufficiently competent to self-administer efgartigimod PH20 SC	Percentage of participants or caregivers determined by the site staff to be sufficiently competent to self-administer efgartigimod PH20 SC	Up to 41 weeks
Secondary	Number of participants or caregivers that self-administer efgartigimod PH20 SC under site staff supervision	Number of participants or caregivers that self-administer efgartigimod PH20 SC under site staff supervision	Up to 41 weeks
Secondary	Percentage of participants or caregivers that self-administer efgartigimod PH20 SC under site staff supervision	Percentage of participants or caregivers that self-administer efgartigimod PH20 SC under site staff supervision	Up to 41 weeks