Trial Outcomes & Findings for A Safety and Dose-Finding Study of SYNT001 in Subjects With Pemphigus (Vulgaris or Foliaceus) (NCT NCT03075904)
NCT ID: NCT03075904
Last Updated: 2020-02-05
Results Overview
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.
TERMINATED
PHASE1/PHASE2
8 participants
Day 1 (after first dose) through Day 112
2020-02-05
Participant Flow
This study was terminated after the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy were characterized at a single dose level (10 milligram/kilogram \[mg/kg\]) in Cohort 1, before any participants were enrolled in Cohort 2. This results disclosure is for Cohort 1 only.
Participant milestones
| Measure |
Cohort 1: ALXN1830
Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
|
|---|---|
|
Overall Study
STARTED
|
8
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
8
|
|
Overall Study
COMPLETED
|
4
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Cohort 1: ALXN1830
Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
|
|---|---|
|
Overall Study
Physician Decision
|
3
|
|
Overall Study
Need for Medication not Permitted
|
1
|
Baseline Characteristics
A Safety and Dose-Finding Study of SYNT001 in Subjects With Pemphigus (Vulgaris or Foliaceus)
Baseline characteristics by cohort
| Measure |
Cohort 1: ALXN1830
n=8 Participants
Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
|
|---|---|
|
Age, Continuous
|
51.4 years
STANDARD_DEVIATION 16.43 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Type of Pemphigus
Vulgaris
|
7 Participants
n=5 Participants
|
|
Type of Pemphigus
Foliaceus
|
1 Participants
n=5 Participants
|
|
Age at Diagnosis of Pemphigus
|
41.3 years
STANDARD_DEVIATION 18.90 • n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 (after first dose) through Day 112Population: All participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Cohort 1: ALXN1830
n=8 Participants
Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
|
|---|---|
|
Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs)
TEAEs
|
7 Participants
|
|
Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs)
Serious TEAEs
|
1 Participants
|
|
Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs)
Discontinuations due to TEAEs
|
0 Participants
|
|
Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs)
Deaths
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline through Day 112Population: All participants who received at least 1 dose of study drug and had postdose pharmacodynamic data available.
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.
Outcome measures
| Measure |
Cohort 1: ALXN1830
n=8 Participants
Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
|
|---|---|
|
Maximum Percent Reduction Of Mean Total Immunoglobulin G (IgG) Levels From Baseline
|
57.3 percentage of reduction
|
SECONDARY outcome
Timeframe: Baseline through Day 112Population: All participants who received at least 1 dose of study drug and had postdose pharmacodynamic data available.
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.
Outcome measures
| Measure |
Cohort 1: ALXN1830
n=8 Participants
Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
|
|---|---|
|
Maximum Percent Reduction In Mean Pemphigus Disease Area Index (PDAI) Total Activity Score From Baseline
|
45.7 percentage of reduction
|
SECONDARY outcome
Timeframe: Baseline through Day 112Population: All participants who received at least 1 dose of study drug and had postdose pharmacodynamic data available.
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.
Outcome measures
| Measure |
Cohort 1: ALXN1830
n=8 Participants
Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
|
|---|---|
|
Maximum Percent Reduction Of Mean Circulating Immune Complexes (CIC) Levels From Baseline
|
51.4 percentage of reduction
|
SECONDARY outcome
Timeframe: Baseline through Day 112Population: All participants who received at least 1 dose of study drug and had postdose pharmacodynamic data available.
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.
Outcome measures
| Measure |
Cohort 1: ALXN1830
n=8 Participants
Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
|
|---|---|
|
Maximum Percent Reduction Of Mean Anti-Desmoglein (Dsg) 1 And 3 Antibodies From Baseline
anti-Dsg 1
|
8.9 percentage of reduction
|
|
Maximum Percent Reduction Of Mean Anti-Desmoglein (Dsg) 1 And 3 Antibodies From Baseline
anti-Dsg 3
|
20.4 percentage of reduction
|
Adverse Events
Cohort 1: ALXN1830
Serious adverse events
| Measure |
Cohort 1: ALXN1830
n=8 participants at risk
Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
|
|---|---|
|
General disorders
Disease progression
|
12.5%
1/8 • Baseline through Day 112
|
|
Renal and urinary disorders
Acute kidney injury
|
12.5%
1/8 • Baseline through Day 112
|
Other adverse events
| Measure |
Cohort 1: ALXN1830
n=8 participants at risk
Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
|
|---|---|
|
Eye disorders
Dry eye
|
12.5%
1/8 • Baseline through Day 112
|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
1/8 • Baseline through Day 112
|
|
Gastrointestinal disorders
Nausea
|
25.0%
2/8 • Baseline through Day 112
|
|
Gastrointestinal disorders
Vomiting
|
12.5%
1/8 • Baseline through Day 112
|
|
General disorders
Fatigue
|
25.0%
2/8 • Baseline through Day 112
|
|
General disorders
Malaise
|
12.5%
1/8 • Baseline through Day 112
|
|
General disorders
Pyrexia
|
12.5%
1/8 • Baseline through Day 112
|
|
Hepatobiliary disorders
Hepatic cyst
|
12.5%
1/8 • Baseline through Day 112
|
|
Infections and infestations
Herpes simplex
|
12.5%
1/8 • Baseline through Day 112
|
|
Infections and infestations
Staphylococcal infection
|
12.5%
1/8 • Baseline through Day 112
|
|
Infections and infestations
Tinea barbae
|
12.5%
1/8 • Baseline through Day 112
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
12.5%
1/8 • Baseline through Day 112
|
|
Investigations
Urine analysis abnormal
|
12.5%
1/8 • Baseline through Day 112
|
|
Nervous system disorders
Headache
|
75.0%
6/8 • Baseline through Day 112
|
|
Nervous system disorders
Sinus headache
|
12.5%
1/8 • Baseline through Day 112
|
|
Renal and urinary disorders
Acute kidney injury
|
12.5%
1/8 • Baseline through Day 112
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
12.5%
1/8 • Baseline through Day 112
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.5%
1/8 • Baseline through Day 112
|
|
Vascular disorders
Pallor
|
12.5%
1/8 • Baseline through Day 112
|
Additional Information
Alexion Pharmaceuticals, Inc.
Alexion Pharmaceuticals, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding study results for a period that is less than or equal to 60 days from the date that the communication is submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot unilaterally extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER