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)
Overview
- Phase
- Phase 3
- Intervention
- efgartigimod PH20 SC
- Conditions
- Pemphigus Vulgaris
- Sponsor
- argenx
- Enrollment
- 222
- Locations
- 134
- Primary Endpoint
- Number of Pemphigus Vulgaris (PV) Participants Who Achieve Complete Clinical Remission (CR) on Minimal Prednisone Therapy
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a prospective, multicenter, randomized, double-blinded, placebo-controlled trial to investigate the efficacy, safety, patient outcome measures, tolerability, immunogenicity, PK, and PD of efgartigimod PH20 SC in adult participants aged from 18 years with PV or PF. The trial comprises a screening period of up to 3 weeks, a treatment period of up to 30 weeks, and an 8-week follow-up period for participants who do not enroll into the open-label extension (OLE) trial ARGX-113-1905. The primary objective of the ARGX-113-1904 trial is to demonstrate the efficacy of subcutaneous administration of efgartigimod co-formulated with recombinant human hyaluronidase PH20 (Efgartigimod PH20 SC) compared to placebo in the treatment of participants with Pemphigus Vulgaris (PV). Secondary objectives are to also demonstrate the efficacy of efgartigimod PH20 SC in the treatment of participants with Pemphigus Foliaceus (PF), and to demonstrate early onset of action and a prednisone-sparing effect. After confirmation of eligibility, participants will be randomized in a 2: 1 ratio to receive efgartigimod PH20 SC or placebo
Investigators
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 is male or female, and aged from 18 years at the time of signing the informed consent form (ICF).
- •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).
- •The participant meets one of the following profiles:
- •Newly diagnosed disease with PDAI ≥15 at baseline and naïve to treatment
- •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.
- •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.
- •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.
- •Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating clinical trials and:
- •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.
Exclusion Criteria
- •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.
- •Participants with mild disease severity as defined by PDAI \<15 at baseline.
- •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).
- •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.
- •Use of any monoclonal antibody (including rituximab or another anti-CD20 biologic) within 6 months before the baseline visit.
- •Known hypersensitivity to any of the components of the administered treatments.
- •The participant has a known contraindication to oral prednisone.
- •The participant has a history of refractory disease, as defined by a failure to respond to first-line and second-line therapies
- •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,
Arms & Interventions
efgartigimod PH20 SC
patients receiving efgartigimod PH20 SC on top of prednisone
Intervention: efgartigimod PH20 SC
efgartigimod PH20 SC
patients receiving efgartigimod PH20 SC on top of prednisone
Intervention: prednisone
placebo
patients receiving placebo on top of prednisone
Intervention: Placebo
placebo
patients receiving placebo on top of prednisone
Intervention: prednisone
Outcomes
Primary Outcomes
Number of Pemphigus Vulgaris (PV) Participants Who Achieve Complete Clinical Remission (CR) on Minimal Prednisone Therapy
Time Frame: up to 30 weeks treatment period
Proportion of participants with pemphigus vulgaris who had CRmin within 30 weeks, defined as the absence of new lesions and complete healing of established lesions while the participant was receiving prednisone at ≤10 mg/day for at least 8 weeks.
Secondary Outcomes
- Number of Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF) Participants Who Achieve Complete Clinical Remission (CR) on Minimal Prednisone Therapy Within 30 Weeks(up to 30 weeks treatment period)
- Normalized Cumulative Prednisone Dose During the Treatment Period in Pemphigus Vulgaris Participants(Up to 30 weeks)
- Time to Complete Clinical Remission (CR) in Pemphigus Vulgaris Participants(Up to 30 weeks)
- Time to Disease Control (DC) in Pemphigus Vulgaris (PV) Participants(Up to 30 weeks)
- Normalized Cumulative Prednisone Dose During the Treatment Period in Pemphigus Vulgaris and Pemphigus Foliaceus Participants(Up to 30 weeks)
- Time to Complete Clinical Remission (CR) in Pemphigus Vulgaris and Pemphigus Foliaceus Participants(Up to 30 weeks)
- Time to Disease Control in Pemphigus Vulgaris and Pemphigus Foliaceus Participants(Up to 30 weeks)