Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04598451




Registration number
NCT04598451
Ethics application status
Date submitted
8/10/2020
Date registered
22/10/2020
Date last updated
22/09/2023

Titles & IDs
Public title
A Study to Assess the Efficacy and Safety 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)
Secondary ID [1] 0 0
ARGX-113-1904
Universal Trial Number (UTN)
Trial acronym
ADDRESS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pemphigus Vulgaris 0 0
Pemphigus Foliaceus 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - efgartigimod PH20 SC
Other interventions - Placebo
Treatment: Drugs - prednisone

Experimental: efgartigimod PH20 SC - patients receiving efgartigimod PH20 SC on top of prednisone

Experimental: placebo - patients receiving placebo on top of prednisone


Treatment: Other: efgartigimod PH20 SC
Subcutaneous injection of efgartigimod using rHuPH20 (PH20) as a permeation enhancer

Other interventions: Placebo
Subcutaneous injection of placebo

Treatment: Drugs: prednisone
Oral prednisone tablets
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of Pemphigus Vulgaris (PV) participants who achieve complete clinical remission (CR) on minimal Prednisone therapy
Timepoint [1] 0 0
30 weeks treatment period
Secondary outcome [1] 0 0
Proportion of Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF) participants who achieve complete clinical remission (CR) on minimal Prednisone therapy
Timepoint [1] 0 0
30 weeks treatment period
Secondary outcome [2] 0 0
Cumulative prednisone dose over the trial in Pemphigus Vulgaris participants
Timepoint [2] 0 0
Up to 30 weeks
Secondary outcome [3] 0 0
Time to complete clinical remission in Pemphigus Vulgaris participants
Timepoint [3] 0 0
Up to 30 weeks
Secondary outcome [4] 0 0
Time to Disease Control (DC) in Pemphigus Vulgaris (PV) participants
Timepoint [4] 0 0
Up to 30 weeks
Secondary outcome [5] 0 0
Proportion of Pemphigus Foliaceus (PF) participants who achieve complete clinical remission (CR) on minimal prednisone therapy
Timepoint [5] 0 0
30 weeks treatment period
Secondary outcome [6] 0 0
Cumulative prednisone dose over the trial in Pemphigus Vulgaris and Pemphigus Foliaceus participants
Timepoint [6] 0 0
Up to 30 weeks
Secondary outcome [7] 0 0
Time to complete clinical remission in Pemphigus Vulgaris and Pemphigus Foliaceus participants
Timepoint [7] 0 0
Up to 30 weeks
Secondary outcome [8] 0 0
Time to disease control in Pemphigus Vulgaris and Pemphigus Foliaceus participants
Timepoint [8] 0 0
Up to 30 weeks
Secondary outcome [9] 0 0
Rate of treatment failure
Timepoint [9] 0 0
Up to 30 weeks
Secondary outcome [10] 0 0
Rate of flare
Timepoint [10] 0 0
Up to 30 weeks
Secondary outcome [11] 0 0
Pemphigus Disease Area Index at each visit
Timepoint [11] 0 0
Up to 41 weeks
Secondary outcome [12] 0 0
Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE)
Timepoint [12] 0 0
Up to 41 weeks
Secondary outcome [13] 0 0
Severity of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE)
Timepoint [13] 0 0
Up to 41 weeks
Secondary outcome [14] 0 0
Composite Glucocorticoid Toxicity Index (C-GTI) comprising the Aggregate Improvement Score (AIS) and the Cumulative Worsening Score (CWS)
Timepoint [14] 0 0
Up to 30 weeks
Secondary outcome [15] 0 0
EuroQol Five-Dimension Five-Level Scale (EQ-5D-5L) score
Timepoint [15] 0 0
30 weeks treatment period
Secondary outcome [16] 0 0
Autoimmune Bullous Disease Quality of Life (ABQOL) score
Timepoint [16] 0 0
30 weeks treatment period
Secondary outcome [17] 0 0
Efgartigimod serum concentrations
Timepoint [17] 0 0
Up to 38 weeks
Secondary outcome [18] 0 0
Total immunoglobulin G and subtype (IgG1, IgG2, IgG3, IgG4) serum levels
Timepoint [18] 0 0
Up to 41 weeks
Secondary outcome [19] 0 0
Anti desmoglein-1 and -3 autoantibodies serum levels
Timepoint [19] 0 0
Up to 41 weeks
Secondary outcome [20] 0 0
Incidence of anti-drug antibodies (ADA) to efgartigimod PH20 SC
Timepoint [20] 0 0
Up to 38 weeks
Secondary outcome [21] 0 0
Prevalence of anti-drug antibodies (ADA) to efgartigimod PH20 SC
Timepoint [21] 0 0
Up to 38 weeks
Secondary outcome [22] 0 0
Incidence of antibodies produced against recombinant human hyaluronidase (rHuPH20) (plasma levels)
Timepoint [22] 0 0
Up to 31 weeks
Secondary outcome [23] 0 0
Prevalence of antibodies produced against recombinant human hyaluronidase (rHuPH20)
Timepoint [23] 0 0
Up to 31 weeks
Secondary outcome [24] 0 0
Number of participants or caregivers completing the self-administration training
Timepoint [24] 0 0
Up to 41 weeks
Secondary outcome [25] 0 0
Percentage of participants or caregivers completing the self-administration training
Timepoint [25] 0 0
Up to 41 weeks
Secondary outcome [26] 0 0
Number of participants or caregivers determined by the site staff to be sufficiently competent to self-administer efgartigimod PH20 SC
Timepoint [26] 0 0
Up to 41 weeks
Secondary outcome [27] 0 0
Percentage of participants or caregivers determined by the site staff to be sufficiently competent to self-administer efgartigimod PH20 SC
Timepoint [27] 0 0
Up to 41 weeks
Secondary outcome [28] 0 0
Number of participants or caregivers that self-administer efgartigimod PH20 SC under site staff supervision
Timepoint [28] 0 0
Up to 41 weeks
Secondary outcome [29] 0 0
Percentage of participants or caregivers that self-administer efgartigimod PH20 SC under site staff supervision
Timepoint [29] 0 0
Up to 41 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/08/2023
Sample size
Target
Accrual to date
Final
222
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Investigator site 24 - AU0610006 - Sydney
Recruitment hospital [2] 0 0
Investigator site 5 - AU0610007 - Parkville
Recruitment hospital [3] 0 0
Investigator site 103 - AU0610013 - Melbourne
Recruitment postcode(s) [1] 0 0
2217 - Sydney
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment postcode(s) [3] 0 0
3065 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Pleven
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Plovdiv
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Sofia
Country [18] 0 0
China
State/province [18] 0 0
Beijing
Country [19] 0 0
China
State/province [19] 0 0
Chendu
Country [20] 0 0
China
State/province [20] 0 0
Chongqing
Country [21] 0 0
China
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Fujian
Country [22] 0 0
China
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Guangzhou
Country [23] 0 0
China
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Guanzhou
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China
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Nanjing
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China
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Shanghai
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China
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Wuhan
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China
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Zhengzhou
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France
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Bobigny
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France
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La Tronche
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France
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Rouen
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France
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Saint-Étienne
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Georgia
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Tbilisi
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Germany
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Berlin
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Germany
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Dresden
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Germany
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Frankfurt am main
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Germany
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Freiburg
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Germany
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Kiel
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Germany
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Lübeck
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Germany
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Marburg
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Germany
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Tübingen
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Germany
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Ulm
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Germany
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Würzburg
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Greece
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Athens
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Greece
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Chaïdári
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Greece
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Thessaloníki
Country [46] 0 0
Hungary
State/province [46] 0 0
Budapest
Country [47] 0 0
Hungary
State/province [47] 0 0
Debrecen
Country [48] 0 0
Hungary
State/province [48] 0 0
Pécs
Country [49] 0 0
Hungary
State/province [49] 0 0
Szeged
Country [50] 0 0
India
State/province [50] 0 0
Ahmedabad
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India
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Chandigarh
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India
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Lucknow
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India
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Nagpur
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Israel
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Tel Aviv
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Italy
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Lazio
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Italy
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Catania
Country [57] 0 0
Italy
State/province [57] 0 0
Firenze
Country [58] 0 0
Italy
State/province [58] 0 0
Genova
Country [59] 0 0
Italy
State/province [59] 0 0
Perugia
Country [60] 0 0
Italy
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Roma
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Italy
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Siena
Country [62] 0 0
Japan
State/province [62] 0 0
Aichi
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Japan
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Hiroshima
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Japan
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Kurume
Country [65] 0 0
Japan
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Kofu
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Japan
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Okayama
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Japan
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Osaka
Country [68] 0 0
Japan
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Sapporo
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Japan
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Sendai
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Japan
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Tokyo
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Poland
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Katowice
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Poland
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Poznan
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Poland
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Rzeszów
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Poland
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Wroclaw
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Poland
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Lódz
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Romania
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Bucharest
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Romania
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Cluj-Napoca
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Romania
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Iasi
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Russian Federation
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Chelyabinsk
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Russian Federation
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Ekaterinburg
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Russian Federation
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Kazan
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Russian Federation
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Krasnodar
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Russian Federation
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Rostov-on-Don
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Russian Federation
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Saint Petersburg
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Russian Federation
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Saratov
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Serbia
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Belgrade
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Serbia
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Belgrad
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Serbia
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Niš
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Serbia
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Novi Sad
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Spain
State/province [90] 0 0
Barcelona
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Spain
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Granada
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Spain
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Madrid
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Spain
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Málaga
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Spain
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Pamplona
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Spain
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Sevilla
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Turkey
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Gaziantep
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Turkey
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Istanbul
Country [98] 0 0
Ukraine
State/province [98] 0 0
Dnipro
Country [99] 0 0
Ukraine
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Ivano-Frankivs'k
Country [100] 0 0
Ukraine
State/province [100] 0 0
Kyiv
Country [101] 0 0
Ukraine
State/province [101] 0 0
Lviv
Country [102] 0 0
Ukraine
State/province [102] 0 0
Zaporizhzhia
Country [103] 0 0
United Kingdom
State/province [103] 0 0
Birmingham
Country [104] 0 0
United Kingdom
State/province [104] 0 0
Bristol
Country [105] 0 0
United Kingdom
State/province [105] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
argenx
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04598451