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A Safety and Dose-Finding Study of SYNT001 in Subjects With Pemphigus (Vulgaris or Foliaceus)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03075904
Recruitment Status : Terminated (Study objectives achieved)
First Posted : March 9, 2017
Results First Posted : February 5, 2020
Last Update Posted : February 5, 2020
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE March 6, 2017
First Posted Date  ICMJE March 9, 2017
Results First Submitted Date  ICMJE January 16, 2020
Results First Posted Date  ICMJE February 5, 2020
Last Update Posted Date February 5, 2020
Actual Study Start Date  ICMJE July 18, 2017
Actual Primary Completion Date January 16, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2020)
Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Day 1 (after first dose) through Day 112 ]
A TEAE was defined as any adverse event (AE) that starts on or after the first dose of study drug or occurs prior to the first dose and worsens in severity on or after the first dose of study drug, during the Treatment Period and Follow-up Period. A TEAE was considered "serious" (Grade 3) if, in the view of either the investigator or sponsor, it resulted in any of the following outcomes: death, life-threatening adverse drug event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, or an event that may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the previously listed outcomes. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Original Primary Outcome Measures  ICMJE
 (submitted: March 8, 2017)
Assessment of safety data (counts and percentages of adverse events) [ Time Frame: Day 0 - Day 56 ]
counts and percentages of adverse events
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2020)
  • Maximum Percent Reduction Of Mean Total Immunoglobulin G (IgG) Levels From Baseline [ Time Frame: Baseline through Day 112 ]
    Pharmacodynamic samples were collected for analysis throughout the study. The maximum percent reduction of mean serum total IgG levels from Baseline observed during the study is presented.
  • Maximum Percent Reduction In Mean Pemphigus Disease Area Index (PDAI) Total Activity Score From Baseline [ Time Frame: Baseline through Day 112 ]
    Pemphigus severity and disease activity was measured using the PDAI in regions where a validated questionnaire was available. The PDAI was administered during Treatment Period and Follow-up Period. PDAI total activity was comprised of scores for the skin, mucous membrane, and scalp subscales. The investigator determined a PDAI score as 0 to 250 points for total activity score (0 to 120 for skin, 0 to 10 for scalp, and 0 to 120 for mucosa). A higher score indicated higher impact on skin disease. The maximum percent reduction in PDAI total activity score from Baseline observed during the study is presented.
  • Maximum Percent Reduction Of Mean Circulating Immune Complexes (CIC) Levels From Baseline [ Time Frame: Baseline through Day 112 ]
    Pharmacodynamic samples were collected for analysis throughout the study. The maximum percent reduction of mean CIC levels from Baseline observed during the study is presented.
  • Maximum Percent Reduction Of Mean Anti-Desmoglein (Dsg) 1 And 3 Antibodies From Baseline [ Time Frame: Baseline through Day 112 ]
    Pharmacodynamic samples were collected for analysis throughout the study. The maximum percent reduction of mean anti-Dsg 1 and 3 antibodies from Baseline observed during the study is presented.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2017)
  • Pharmacokinetics (serum concentration of SYNT001) [ Time Frame: Day 0, 1, 2, 5, 28, 29, 30, 33 ]
    serum concentration of SYNT001
  • Pemphigus Disease Area Index (PDAI) [ Time Frame: Day 0, 7, 14, 28, 33, 42, 56 ]
    disease activity marker
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety and Dose-Finding Study of SYNT001 in Subjects With Pemphigus (Vulgaris or Foliaceus)
Official Title  ICMJE A Phase 1B/2, Multicenter, Open-Label, Safety, and Dose-Finding Study of SYNT001 in Subjects With Pemphigus (Vulgaris or Foliaceus)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pemphigus
  • Pemphigus Vulgaris
  • Pemphigus Foliaceus
Intervention  ICMJE Drug: ALXN1830
Administered via IV infusion.
Other Name: SYNT001
Study Arms  ICMJE
  • Experimental: Cohort 1: ALXN1830
    Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
    Intervention: Drug: ALXN1830
  • Experimental: Cohort 2: ALXN1830
    Participants were to receive 3 doses of ALXN1830 30 mg/kg administered weekly (loading) followed by 5 doses of ALXN1830 10 mg/kg administered every other week or 10 weekly doses of ALXN1830 IV (maintenance).
    Intervention: Drug: ALXN1830
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 1, 2019)
8
Original Estimated Enrollment  ICMJE
 (submitted: March 8, 2017)
16
Actual Study Completion Date  ICMJE January 16, 2019
Actual Primary Completion Date January 16, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03075904
Other Study ID Numbers  ICMJE SYNT001-103
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  ICMJE
Plan to Share IPD: No
Responsible Party Alexion Pharmaceuticals
Study Sponsor  ICMJE Alexion Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Alexion Pharmaceuticals
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP