Back to resultsA Safety and Dose-Finding Study of SYNT001 in Subjects With Pemphigus (Vulgaris or Foliaceus)
Primary Purpose
Pemphigus, Pemphigus Vulgaris, Pemphigus Foliaceus
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ALXN1830
Sponsored by
About this trial
This is an interventional treatment trial for Pemphigus
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
Sites / Locations
- Alexion Study Site
- Alexion Study Site
- Alexion Study Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1: ALXN1830
Cohort 2: ALXN1830
Arm Description
Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
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).
Outcomes
Primary Outcome Measures
Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs)
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.
Secondary Outcome Measures
Maximum Percent Reduction Of Mean Total Immunoglobulin G (IgG) Levels From Baseline
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
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03075904
Brief Title
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
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Terminated
Why Stopped
Study objectives achieved
Study Start Date
July 18, 2017 (Actual)
Primary Completion Date
January 16, 2019 (Actual)
Study Completion Date
January 16, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pemphigus, Pemphigus Vulgaris, Pemphigus Foliaceus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: ALXN1830
Arm Type
Experimental
Arm Description
Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
Arm Title
Cohort 2: ALXN1830
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
ALXN1830
Other Intervention Name(s)
SYNT001
Intervention Description
Administered via IV infusion.
Primary Outcome Measure Information:
Title
Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Day 1 (after first dose) through Day 112
Secondary Outcome Measure Information:
Title
Maximum Percent Reduction Of Mean Total Immunoglobulin G (IgG) Levels From Baseline
Description
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.
Time Frame
Baseline through Day 112
Title
Maximum Percent Reduction In Mean Pemphigus Disease Area Index (PDAI) Total Activity Score From Baseline
Description
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.
Time Frame
Baseline through Day 112
Title
Maximum Percent Reduction Of Mean Circulating Immune Complexes (CIC) Levels From Baseline
Description
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.
Time Frame
Baseline through Day 112
Title
Maximum Percent Reduction Of Mean Anti-Desmoglein (Dsg) 1 And 3 Antibodies From Baseline
Description
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.
Time Frame
Baseline through Day 112
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Alexion Study Site
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27516
Country
United States
Facility Name
Alexion Study Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Alexion Study Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34126109
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.
Results Reference
derived
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A Safety and Dose-Finding Study of SYNT001 in Subjects With Pemphigus (Vulgaris or Foliaceus)
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