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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 23 November 2020
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: 150
Recruitment status: Authorised-recruitment may be ongoing or finished
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: no
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 France Georgia Germany Greece Hungary India
Israel Italy Japan Poland Romania Russian Federation Spain Turkey
Ukraine United Kingdom United States
Contacts
Name: Regulatory   
Address:  Industriepark Zwijnaarde 7 B-9052 Zwijnaarde Belgium
Telephone: 003293103400
Email: regulatory@argenx.com
Affiliation:  argenx BV
Name: Regulatory   
Address:  Industriepark Zwijnaarde 7 B-9052 Zwijnaarde Belgium
Telephone: 003293103400
Email: regulatory@argenx.com
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 patient is male or female, and aged 18 years to 80 years at the time of signing the informed consent form (ICF).
3. The patient 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 ELISA.
4. The patient 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 patient 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 diagnosis, and off prednisone therapy ± a conventional immunosuppressant (eg, azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil). Note: conventional immunosuppressants must be discontinued before baseline.
d. Experiencing flare with PDAI =15, a maximum of 4 years since diagnosis, 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) for at least 2 weeks and patients are fit to start prednisone treatment at 0.5 mg/kg qd at baseline. Note: conventional
immunosuppressants must be discontinued before baseline.
5. Women of childbearing potential:
a. Must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before trial medication can be
administered.
b. Must be on a stable regimen for at least 1 month of at least 1 highly effective method of contraception (ie, failure rate of less than 1% per year) during the trial and for 90 days after the last administration of IMP.
6. Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use effective contraception from first administration of IMP through 90 days after the last administration of the IMP. Male patients practicing true sexual abstinence (as consistent with preferred and usual life style) can be included. Sterilized male patients who have had a vasectomy and with documented absence of sperm post-procedure can be included. Male patients are not allowed to donate sperm from first administration of IMP through 90 days after 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 105
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

Exclusion criteria:
1. Patient 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. Patients with mild disease severity as defined by PDAI <15 at baseline.
3. Patients 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 patient has been administered therapy other than oral prednisone or conventional immunosuppressants (eg, azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) within 2 months before the baseline visit and that can affect clinical disease activity.
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 patient has a known contraindication to oral prednisone.
8. The patient has a history of refractory disease, as defined by a failure to respond to first-line and second-line therapies.
9. Patients who have a history of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for =3 years before first IMP administration. Patients with any of the following cancers can be included at any time:
a. Adequately treated 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. Patients with clinical evidence of other significant serious disease or patients 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 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 patient has a Karnofsky performance score <60%.
15. Vaccination with live/attenuated viral vaccines within 28 days prior to randomization.
16. The patient 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. Human immunodeficiency virus (HIV)
18. The patient has total immunoglobulin G (IgG) <6 g/L at screening.
19. The patient 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.



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: 100000004858
MedDRA version: 20.0 Level: LLT Classification code 10057069 Term: Pemphigus foliaceus System Organ Class: 100000004858
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

Primary Outcome(s)
Main Objective: To demonstrate the efficacy of efgartigimod PH20 SC compared to placebo in the treatment of patients with Pemphigus vulgaris
Primary end point(s): Proportion of Pemphigus vulgaris patients who achieve complete clinical remission (CR) on minimal prednisone therapy within 30 weeks
Secondary Objective: • To demonstrate the efficacy of efgartigimod PH20 SC in the treatment of patients with pemphigus vulgaris or pemphigus foliaceus
• To assess the safety of efgartigimod PH20 SC in patients with PV or PF
• To evaluate the effects of efgartigimod PH20 SC on quality of life (QoL) in patients with PV or PF
• To evaluate the PK of efgartigimod PH20 SC in patients with PV or PF
• To evaluate the PD of efgartigimod PH20 SC in patients with PV or PF
• To evaluate the immunogenicity of efgartigimod PH20 SC in patients with PV or PF
Timepoint(s) of evaluation of this end point: week 30
Secondary Outcome(s)
Secondary end point(s): 1. Proportion of PV and PF patients who achieve complete clinical CR on minimal prednisone therapy within 30 weeks
2. Time to Disease Control (DC) in PV patients
3. Time to CR in PV patients
4. Cumulative prednisone dose over the trial in PV patients
5. Time to DC in PV and PF patients
6. Time to complete CR in PV and PF patients
7. Cumulative prednisone dose over the trial in PV and PF patientss
8. Rate of treatment failure
9. Rate of flare
10. PDAI at each visit
11. Incidence and severity of TEAEs, AESIs, and SAEs by System Organ Class (SOC) and Preferred Term (PT).
12. EuroQol Five-Dimension Five-Level Scale (EQ-5D-5L) score - 30 weeks treatment period
13. Autoimmune Bullous Quality of Life (ABQOL) score
14. Efgartigimod serum concentrations
15. Total IgG and subtype (IgG1, IgG2, IgG3, IgG4) serum levels
16. Anti Dsg-1 and -3 autoantibodies serum levels
17. Anti-drug antibodies (ADA) to efgartigimod PH20 SC
Timepoint(s) of evaluation of this end point: endpoint 1: 30 weeks treatment period
endpoints 2 to 9; up to 30 weeks
endpoint 10 & 11: up to 41 weeks
endpoint 12 & 13: 30 weeks treatment period
endpoint 14: up to 38 weeks
endpoint 15 & 16: up to 41 weeks
endpoint 17: Up to 38 weeks
Secondary ID(s)
ARGX-113-1904
Source(s) of Monetary Support
argenx BV
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 19/10/2020
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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