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) (ADDRESS+)

• ClinicalTrials.gov Identifier: NCT04598477
• Recruitment Status: Terminated
• First Posted: October 22, 2020
• Last Update Posted: April 24, 2024
• Sponsor: argenx
• Information provided by (Responsible Party): argenx

Tracking Information

• First Submitted Date: October 8, 2020
• First Posted Date: October 22, 2020
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: July 15, 2021
• Actual Primary Completion Date: March 25, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 16, 2020)

• Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE) [ Time Frame: Up to 60 weeks ]
  Incidence 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) [ Time Frame: Up to 60 weeks ]
  Severity of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 27, 2022)

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

Original Secondary Outcome Measures (submitted: October 16, 2020)

• Proportion of Pemphigus Vulgaris (PV) patients who achieve complete clinical remission (CR) on minimal prednisone therapy [ Time Frame: Up to 52 weeks treatment period ]
  Proportion of patients with Pemphigus Vulgaris who achieve complete clinical remission on minimal prednisone therapy.
• Proportion of Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF) patients who achieve complete clinical remission (CR) on minimal prednisone dose therapy [ Time Frame: Up to 52 weeks treatment period ]
  Proportion of patients with Pemphigus Vulgaris and Pemphigus Foliaceus who achieve complete clinical remission on minimal prednisone therapy.
• Time to Disease Control (DC) [ Time Frame: Up to 60 weeks ]
  Time to Disease Control
• Time to complete clinical remission (CR) [ Time Frame: Up to 60 weeks ]
  Time to complete clinical remission
• Time to complete clinical remission (CR) on minimal prednisone therapy [ Time Frame: Up to 60 weeks ]
  Time to complete clinical remission on minimal prednisone therapy
• Time to complete clinical remission (CR) off prednisone therapy [ Time Frame: Up to 60 weeks ]
  Time to complete clinical remission off prednisone therapy
• Time to flare [ Time Frame: Up to 60 weeks ]
• Rate of treatment failure [ Time Frame: Up to 60 weeks ]
• Rate of flare [ Time Frame: Up to 60 weeks ]
• Cumulative prednisone dose over the trial [ Time Frame: Up to 52 weeks treatment period ]
• Pemphigus Disease Area Index (PDAI) at each visit [ Time Frame: Up to 52 weeks treatment period ]
  Pemphigus Disease Area Index at each visit
• EuroQol 5-Dimension 5-Level (EQ-5D-5L) score [ Time Frame: Up to 52 weeks treatment period ]
• Autoimmune Blister Quality of Life (ABQOL) score [ Time Frame: Up to 52 weeks treatment period ]
• Efgartigimod serum concentrations [ Time Frame: Up to 60 weeks ]
• Total Immunoglobulin G and subtype (IgG1, IgG2, IgG3, IgG4) serum levels [ Time Frame: Up to 60 weeks ]
• Anti-Desmoglein -1 and -3 autoantibodies serum levels [ Time Frame: Up to 60 weeks ]
• Anti-drug antibodies (ADAs) to efgartigimod (serum levels) and recombinant human hyaluronidase PH20 (plasma levels) [ Time Frame: Up to 60 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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

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

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Pemphigus Vulgaris
• Pemphigus Foliaceus

Intervention

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

Study Arms

Experimental: efgartigimod PH20 SC

patients receiving efgartigimod PH20 SC on top of prednisone

Interventions:

• Biological: efgartigimod PH20 SC
• Drug: prednisone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: January 17, 2024): 183
• Original Estimated Enrollment (submitted: October 16, 2020): 150
• Actual Study Completion Date: March 25, 2024
• Actual Primary Completion Date: March 25, 2024 (Final data collection date for primary outcome measure)

Eligibility 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 participated in trial ARGX-113-1904 and completed the study or has the defined criteria for rollover.

3. Contraceptive use by men and women should be consistent with local regulations regarding the methods for contraception for those participating in clinical trials and:

   1. 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.

   2. 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:

1. Pregnant and lactating women and those intending to become pregnant during the trial.
2. 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.
3. Known hypersensitivity to any of the components of the administered treatments.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Bulgaria, China, France, Georgia, Germany, Greece, Hungary, India, Israel, Italy, Japan, Poland, Romania, Russian Federation, Serbia, Spain, Turkey, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04598477
• Other Study ID Numbers: ARGX-113-1905
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: argenx
• Original Responsible Party: Same as current
• Current Study Sponsor: argenx
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: argenx
• Verification Date: April 2024