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

Study Overview
=================
Brief Summary
-----------------
This is a prospective, multicenter, open label extension (OLE) trial on the efficacy, safety, patient outcome measures, tolerability, immunogenicity, PK and PD of efgartigimod PH20 SC in adult PV or PF participants, who participated in antecedent trial ARGX-113-1904. This trial provides extension of efgartigimod PH20 SC treatment and retreatment options for participants who have been randomized to efgartigimod PH20 SC treatment arm in the trial ARGX-113-1904, and the first treatment of efgartigimod PH20 SC and retreatment options for participants who had been randomized to placebo arm in trial ARGX-113-1904. Trial ARGX-113-1905 evaluates ability to (further) taper prednisone therapy and achieve Clinical Remission (CR) off therapy (CRoff), the ability to achieve CR and CR on minimal therapy (CRmin) for participants who had not yet achieved CRmin, and the ability to treat flare; and assess patient outcome measures and the safety, PD, PK and immunogenicity of efgartigimod PH20 SC over the duration of trial. Study duration: Up to 60 weeks for participants who receive IMP administration up to 52 weeks and with a follow-up period of 8 weeks after the last IMP administration

Official Title
-----------------
An Open-Label, Multicenter, Follow-up Trial of ARGX-113-1904 to Evaluate the Safety, Tolerability, and Efficacy of Efgartigimod PH20 SC in Patients With Pemphigus

Conditions
-----------------
Pemphigus Vulgaris, Pemphigus Foliaceus

Intervention / Treatment
-----------------
* Biological: efgartigimod PH20 SC
* Drug: prednisone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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). The participant participated in trial ARGX-113-1904 and completed the study or has the defined criteria for rollover. Contraceptive use by men and women should be consistent with local regulations regarding the methods for contraception for those participating in clinical trials and: Male participants: Male participants must agree to use an acceptable method of contraception as described in the protocol, from signing the ICF until the last dose of the study drug. Female participants Women of childbearing potential (WOCBP) must: have a negative urine pregnancy test at baseline before the IMP can be administered, agree to use a highly effective or acceptable contraception method (as described in the protocol), which should be maintained at minimum until after the last dose of IMP Exclusion Criteria: Pregnant and lactating women and those intending to become pregnant during the trial. 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. Known hypersensitivity to any of the components of the administered treatments.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: efgartigimod PH20 SC<br>patients receiving efgartigimod PH20 SC on top of prednisone | Biological: efgartigimod PH20 SC<br>* Subcutaneous injection of efgartigimod using rHuPH20 (PH20) as a permeation enhancer<br>Drug: prednisone<br>* Oral prednisone tablets<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE) | Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE) | Up to 60 weeks | 
| Severity of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE) | Severity of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE) | Up to 60 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Pemphigus Vulgaris (PV) participants who achieve complete clinical remission (CR) on minimal prednisone therapy | Proportion of participants with Pemphigus Vulgaris who achieve complete clinical remission on minimal prednisone therapy. | Up to 52 weeks treatment period | 
| Proportion of Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF) participants who achieve complete clinical remission (CR) on minimal prednisone dose therapy | Proportion of participants with Pemphigus Vulgaris and Pemphigus Foliaceus who achieve complete clinical remission on minimal prednisone therapy. | Up to 52 weeks treatment period | 
| Time to Disease Control (DC) | Time to Disease Control | Up to 60 weeks | 
| Time to complete clinical remission (CR) | Time to complete clinical remission | Up to 60 weeks | 
| Time to complete clinical remission (CR) on minimal prednisone therapy | Time to complete clinical remission on minimal prednisone therapy | Up to 60 weeks | 
| Time to complete clinical remission (CR) off prednisone therapy | Time to complete clinical remission off prednisone therapy | Up to 60 weeks | 
| Time to flare | Time to flare | Up to 60 weeks | 
| Rate of treatment failure | Rate of treatment failure | Up to 60 weeks | 
| Rate of flare | Rate of flare | Up to 60 weeks | 
| Cumulative prednisone dose over the trial | Cumulative prednisone dose over the trial | Up to 52 weeks treatment period | 
| Pemphigus Disease Area Index (PDAI) at each visit | Pemphigus Disease Area Index at each visit | Up to 52 weeks treatment period | 
| EuroQol 5-Dimension 5-Level (EQ-5D-5L) score | EuroQol 5-Dimension 5-Level score | Up to 52 weeks treatment period | 
| Autoimmune Blister Quality of Life (ABQOL) score | Autoimmune Blister Quality of Life score | Up to 52 weeks treatment period | 
| Efgartigimod serum concentrations | Efgartigimod serum concentrations | Up to 60 weeks | 
| Total Immunoglobulin G and subtype (IgG1, IgG2, IgG3, IgG4) serum levels | Total Immunoglobulin G and subtype (IgG1, IgG2, IgG3, IgG4) serum levels | Up to 60 weeks | 
| Anti-desmoglein (Dsg) -1 and -3 autoantibodies serum levels | Anti-desmoglein (Dsg) -1 and -3 autoantibodies serum levels | Up to 60 weeks | 
| Incidence of antidrug antibodies (ADA) against efgartigimod PH20 SC | Incidence of antidrug antibodies (ADA) against efgartigimod PH20 SC | Up to 60 weeks | 
| Prevalence of antidrug antibodies (ADA) against efgartigimod PH20 SC | Prevalence of antidrug antibodies (ADA) against efgartigimod PH20 SC | Up to 60 weeks | 
| 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 52 weeks treatment period | 
| Percentage of participants who performed self-administration | Percentage of participants who performed self-administration | Up to 52 weeks | 
| Percentage of caregivers who administered the injection to the participant | Percentage of caregivers who administered the injection to the participant | Up to 52 weeks | 
| Number of visits needed for the participant or caregiver to be competent to start administering efgartigimod PH20 SC | Number of visits needed for the participant or caregiver to be competent to start administering efgartigimod PH20 SC | Up to 52 weeks | 
| Frequency of self- or caregiver-supported administration at home | Frequency of self- or caregiver-supported administration at home | Up to 52 weeks |