Clinical trial NCT03075904: A Safety and Dose-Finding Study of SYNT001 in Subjects With Pemphigus (Vulgaris or Foliaceus)
Official title: A Phase 1B/2, Multicenter, Open-Label, Safety, and Dose-Finding Study of SYNT001 in Subjects With Pemphigus (Vulgaris or Foliaceus)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Pemphigus
Pemphigus Vulgaris
Pemphigus Foliaceus
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2017-03-09
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This was a multicenter, open-label safety study to determine the dose regimen of SYNT001 (ALXN1830) administered intravenously in participants with pemphigus (vulgaris or foliaceus).

Detailed description: This study planned to evaluate 2 cohorts: up to 8 participants to receive 5 weekly intravenous (IV) doses of ALXN1830 at 10 milligram/kilogram (mg/kg) (Cohort 1) and up to 12 participants to receive 3 x 30 mg/kg weekly doses of ALXN1830 IV (loading) followed by 5 x 10 mg/kg doses of ALXN1830 IV every other week or 10 weekly doses of ALXN1830 IV (maintenance) (Cohort 2).

This study was terminated after the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy were characterized in participants with pemphigus at a single dose level (10 mg/kg) in Cohort 1, before any participants were enrolled in Cohort 2.

The study consisted of 3 periods: Screening, Treatment, and Follow-Up.

Eligibility criteria: Inclusion Criteria:

Participants must have meet the following criteria to be included:

* Were willing and able to read, understand and sign an informed consent form
* Documented diagnosis of pemphigus vulgaris or foliaceus
* Were required to use medically acceptable contraception

Exclusion Criteria:

Participants meeting any of the following criteria were excluded:

* Were unable or unwilling to comply with the protocol
* Active non-hematologic malignancy or history of non-hematologic malignancy in the 3 years prior to screening (exclusive of non-melanoma skin cancer and cervical cancer in situ)
* Positive for human immunodeficiency virus (HIV) or hepatitis C antibody
* Positive for hepatitis B surface antigen
* IV immunoglobulin treatment within 30 days of screening
* Any exposure to an investigational drug or device within the 30 days prior to screening
* Plasmapheresis or immunoadsorption within 30 days of screening
* Participant had any current medical condition that, in the opinion of the Investigator, may have compromised their safety or compliance, preclude successful conduct of the study, or interfere with interpretation of the results

Primary outcomes:
measure: Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 (after first dose) through Day 112
Secondary outcomes:
measure: Maximum Percent Reduction Of Mean Total Immunoglobulin G (IgG) Levels From Baseline
timeFrame: Baseline through Day 112
measure: Maximum Percent Reduction In Mean Pemphigus Disease Area Index (PDAI) Total Activity Score From Baseline
timeFrame: Baseline through Day 112
measure: Maximum Percent Reduction Of Mean Circulating Immune Complexes (CIC) Levels From Baseline
timeFrame: Baseline through Day 112
measure: Maximum Percent Reduction Of Mean Anti-Desmoglein (Dsg) 1 And 3 Antibodies From Baseline
timeFrame: Baseline through Day 112
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Alexion Study Site
state: North Carolina
city: Durham
country: United States
facility: Alexion Study Site
state: North Carolina
city: Philadelphia
country: United States
facility: Alexion Study Site
state: Pennsylvania
Study officials:
References:
citation: Werth VP, Culton DA, Concha JSS, Graydon JS, Blumberg LJ, Okawa J, Pyzik M, Blumberg RS, Hall RP 3rd. Safety, Tolerability, and Activity of ALXN1830 Targeting the Neonatal Fc Receptor in Chronic Pemphigus. J Invest Dermatol. 2021 Dec;141(12):2858-2865.e4. doi: 10.1016/j.jid.2021.04.031. Epub 2021 Jun 12.