A study to assess the safety and efficacy of a subcutaneous formulation of efgartigimod PH20 SC in adults with Pemphigus (Vulgaris or Foliaceus)

• Register: EUCTR
• Last refreshed on: 12 March 2024
• Main ID: EUCTR2020-002915-23-HU
• Date of registration: 21/09/2020
• Prospective Registration: Yes
• Primary sponsor: argenx BV
• Public title: A study to assess the safety and efficacy of a subcutaneous formulation of efgartigimod PH20 SC in adults with Pemphigus (Vulgaris or Foliaceus)
• Scientific 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) (ADDRESS) - ADDRESS
• Date of first enrolment: 16/11/2020
• Target sample size: 213
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-002915-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Regulatory
• Affiliation: argenx BV

• Name: Regulatory
• Affiliation: argenx BV

Key inclusion & exclusion 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 that has been confirmed by cutaneous histology, positive direct immunofluorescence (IF), and positive indirect IF and/or ELISA.
4. The participant meets 1 of the following profiles:
a. Newly diagnosed disease with PDAI =15 at baseline and naïve to treatment.
b. 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.
c. Experiencing flare with PDAI =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 =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.
5. 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, from signing the ICF until the last dose of IMP.
b. Female participants:
- Women of childbearing potential must:
--have a negative serum pregnancy test at screening and a 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 the last dose of IMP.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 149
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 64

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 Participant has achieved DC or a substantial reduction in PDAI activity score during screening period).
4. The Participant has been administered therapy 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, dapsone, 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.
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)
b. Hepatitis C Virus (HCV)
c. HIV based on test results that are associated with an AIDS-defining or a CD4 count < =200 cells/mm3
18. The participant has total immunoglobulin G (IgG) <6 g/L

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pemphigus Vulgaris or Pemphigus Foliaceus
MedDRA version: 20.0 Level: LLT Classification code 10052802 Term: Pemphigus vulgaris System Organ Class: 10040785 - Skin and subcutaneous tissue disorders
MedDRA version: 20.0 Level: LLT Classification code 10057069 Term: Pemphigus foliaceus System Organ Class: 10040785 - Skin and subcutaneous tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Efgartigimod PH20 SC
Pharmaceutical Form: Solution for injection
INN or Proposed INN: EFGARTIGIMOD ALFA
CAS Number: 1821402-21-4
Current Sponsor code: ARGX-113
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 165-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: Efgartigimod PH20 SC
Pharmaceutical Form: Solution for injection
INN or Proposed INN: EFGARTIGIMOD ALFA
CAS Number: 1821402-21-4
Current Sponsor code: ARGX-113
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 180-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: • To demonstrate the efficacy of efgartigimod PH20 SC in the treatment of participants with pemphigus vulgaris or pemphigus foliaceus
• To assess the safety of efgartigimod PH20 SC in participants with PV or PF
• To assess the health impact of glucocorticoid (GC) use in participants with PV or PF
• To evaluate the effects of efgartigimod PH20 SC on quality of life (QoL) in participants with PV or PF
• To evaluate the PK of efgartigimod PH20 SC in participants with PV or PF
• To evaluate the PD of efgartigimod PH20 SC in participants with PV or PF
• To evaluate the immunogenicity of efgartigimod PH20 SC in participants with PV or PF
• To evaluate the competency of participants or caregivers to self-administer efgartigimod PH20 SC

Main Objective: To demonstrate the efficacy of efgartigimod PH20 SC compared to placebo in the treatment of participants with Pemphigus vulgaris

Timepoint(s) of evaluation of this end point: week 30

Primary end point(s): Proportion of Pemphigus vulgaris participants who achieve CR min therapy within 30 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: endpoints 1 to 10: up to 30 weeks
endpoints 11 to 12: up to 41 weeks
endpoints 13 to 15: up to 30 weeks
endpoint 16: up to 38 weeks
endpoints 17 to 18: up to 41 weeks
endpoint 19: up to 38 weeks
Endpoints 20 to 22: up to 41 weeks

Secondary end point(s): 1. Proportion of PV and PF participants who achieve CR min within 30 weeks
2. Cumulative prednisone dose over the trial in PV participants
3. Time to Disease Control (DC) in PV participants
4. Time to CR in PV participants
5. Proportion of PF participants who achieve CR min within 30 weeks
6. Cumulative prednisone dose over the trial in PV and PF participants
7. Time to CR in PV and PF participants
8. Time to DC in PV and PF participants
9. Rate of treatment failure
10. Rate of flare
11. PDAI at each visit
12. Incidence and severity of treatment-emergent adverse events (TEAEs), AESIs, and SAEs by system organ class (SOC) and preferred term (PT).
13. Composite Glucocorticoid Toxicity Index (C GTI) comprising the Aggregate Improvement Score (AIS) and the Cumulative Worsening Score (CWS)
14. EuroQol Five-Dimension Five-Level Scale (EQ-5D-5L) scale
15. Autoimmune Bullous Disease Quality of Life (ABQOL) score
16. Efgartigimod serum concentrations
17. Total IgG and subtype (IgG1, IgG2, IgG3, IgG4) serum levels
18. Anti Dsg-1 and -3 autoantibodies serum levels
19. Incidence and Prevalence of Anti-drug antibodies (ADA) to efgartigimod (serum levels) and antibodies produced against recombinant human hyaluronidase (rHuPH20) (plasma levels)
20. Number and percentage of participants or caregivers completing the self-administration training
21. Number and percentage of participants or caregivers determined by the site staff to be sufficiently competent to self-administer efgartigimod PH20 SC
22. Number and percentage of participants or caregivers that self-administer efgartigimod PH20 SC under site staff supervision

Secondary ID(s)

2020-002915-23-DE

ARGX-113-1904

Source(s) of Monetary Support

argenx BV

Ethics review

Status: Approved
Approval date: 19/10/2020
Contact: