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

• ClinicalTrials.gov Identifier: NCT03075904
• Recruitment Status: Terminated
• First Posted: March 9, 2017
• Results First Posted: February 5, 2020
• Last Update Posted: February 5, 2020
• Sponsor: Alexion Pharmaceuticals
• Information provided by (Responsible Party): Alexion Pharmaceuticals

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).

Condition or disease	Intervention/treatment	Phase
Pemphigus; Pemphigus Vulgaris; Pemphigus Foliaceus	Drug: ALXN1830	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1B/2, Multicenter, Open-Label, Safety, and Dose-Finding Study of SYNT001 in Subjects With Pemphigus (Vulgaris or Foliaceus)
• Actual Study Start Date: July 18, 2017
• Actual Primary Completion Date: January 16, 2019
• Actual Study Completion Date: January 16, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1: ALXN1830; Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.	Drug: ALXN1830; Administered via IV infusion.; Other Name: SYNT001
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).	Drug: ALXN1830; Administered via IV infusion.; Other Name: SYNT001

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, North Carolina

Alexion Study Site

Chapel Hill, North Carolina, United States, 27516

Alexion Study Site

Durham, North Carolina, United States, 27710

United States, Pennsylvania

Alexion Study Site

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Alexion Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Alexion Pharmaceuticals:

Statistical Analysis Plan  [PDF] March 25, 2019

Study Protocol  [PDF] September 18, 2018

More Information

• Responsible Party: Alexion Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03075904
• Other Study ID Numbers: SYNT001-103
• First Posted: March 9, 2017
• Results First Posted: February 5, 2020
• Last Update Posted: February 5, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Pemphigus; Skin Diseases, Vesiculobullous; Skin Diseases; Autoimmune Diseases; Immune System Diseases