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 Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Pemphigus; Pemphigus Vulgaris; Pemphigus Foliaceus
• Intervention: Drug: ALXN1830
• Enrollment: 8

Participant Flow

Recruitment Details
Pre-assignment Details	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.

Arm/Group Title	Cohort 1: ALXN1830
Arm/Group Description	Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
Period Title: Overall Study
Started	8
Received at Least 1 Dose of Study Drug	8
Completed [1]	4
Not Completed	4
Reason Not Completed
Physician Decision	3
Need for Medication not Permitted	1
[1] All 8 participants received all 5 weekly doses of ALXN1830 10 mg/kg in the Treatment Period.

Baseline Characteristics

Arm/Group Title		Cohort 1: ALXN1830
Arm/Group Description		Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
Overall Number of Baseline Participants		8
Baseline Analysis Population Description		All participants who were enrolled in the study.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	8 participants
		51.4 (16.43)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants
	Female	5 62.5%
	Male	3 37.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	8 100.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	3 37.5%
	White	5 62.5%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Type of Pemphigus; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	8 participants
Vulgaris		7 87.5%
Foliaceus		1 12.5%
Age at Diagnosis of Pemphigus; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	8 participants
		41.3 (18.90)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug.

Arm/Group Title	Cohort 1: ALXN1830
Arm/Group Description:	Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
Overall Number of Participants Analyzed	8
Measure Type: Count of Participants; Unit of Measure: Participants
TEAEs	7 87.5%
Serious TEAEs	1 12.5%
Discontinuations due to TEAEs	0 0.0%
Deaths	0 0.0%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had postdose pharmacodynamic data available.

Arm/Group Title	Cohort 1: ALXN1830
Arm/Group Description:	Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
Overall Number of Participants Analyzed	8
Measure Type: Number; Unit of Measure: percentage of reduction
	57.3

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had postdose pharmacodynamic data available.

Arm/Group Title	Cohort 1: ALXN1830
Arm/Group Description:	Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
Overall Number of Participants Analyzed	8
Measure Type: Number; Unit of Measure: percentage of reduction
	45.7

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had postdose pharmacodynamic data available.

Arm/Group Title	Cohort 1: ALXN1830
Arm/Group Description:	Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
Overall Number of Participants Analyzed	8
Measure Type: Number; Unit of Measure: percentage of reduction
	51.4

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had postdose pharmacodynamic data available.

Arm/Group Title	Cohort 1: ALXN1830
Arm/Group Description:	Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
Overall Number of Participants Analyzed	8
Measure Type: Number; Unit of Measure: percentage of reduction
anti-Dsg 1	8.9
anti-Dsg 3	20.4

Adverse Events

Time Frame	Baseline through Day 112
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Cohort 1: ALXN1830
Arm/Group Description	Participants received 5 doses of ALXN1830 10 mg/kg administered weekly.
All-Cause Mortality
	Cohort 1: ALXN1830
	Affected / at Risk (%)
Total	0/8 (0.00%)
Serious Adverse Events
	Cohort 1: ALXN1830
	Affected / at Risk (%)
Total	1/8 (12.50%)
General disorders
Disease progression † 1 [1]	1/8 (12.50%)
Renal and urinary disorders
Acute kidney injury † 1 [1]	1/8 (12.50%)
1 Term from vocabulary, MedDRA 19.1; † Indicates events were collected by systematic assessment; [1] Resolved and was considered to be not related to the study drug by the Investigator.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Cohort 1: ALXN1830
	Affected / at Risk (%)
Total	7/8 (87.50%)
Eye disorders
Dry eye † 1	1/8 (12.50%)
Gastrointestinal disorders
Diarrhoea † 1	1/8 (12.50%)
Nausea † 1	2/8 (25.00%)
Vomiting † 1	1/8 (12.50%)
General disorders
Fatigue † 1	2/8 (25.00%)
Malaise † 1	1/8 (12.50%)
Pyrexia † 1	1/8 (12.50%)
Hepatobiliary disorders
Hepatic cyst † 1	1/8 (12.50%)
Infections and infestations
Herpes simplex † 1	1/8 (12.50%)
Staphylococcal infection † 1	1/8 (12.50%)
Tinea barbae † 1	1/8 (12.50%)
Injury, poisoning and procedural complications
Infusion related reaction † 1	1/8 (12.50%)
Investigations
Urine analysis abnormal † 1	1/8 (12.50%)
Nervous system disorders
Headache † 1	6/8 (75.00%)
Sinus headache † 1	1/8 (12.50%)
Renal and urinary disorders
Acute kidney injury † 1	1/8 (12.50%)
Skin and subcutaneous tissue disorders
Hyperhidrosis † 1	1/8 (12.50%)
Rash † 1	1/8 (12.50%)
Vascular disorders
Pallor † 1	1/8 (12.50%)
1 Term from vocabulary, MedDRA 19.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Alexion Pharmaceuticals, Inc.
• Organization: Alexion Pharmaceuticals, Inc.
• Phone: 855-752-2356
• EMail: clinicaltrials@alexion.com

• Responsible Party: Alexion Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03075904
• Other Study ID Numbers: SYNT001-103
• First Submitted: March 6, 2017
• First Posted: March 9, 2017
• Results First Submitted: January 16, 2020
• Results First Posted: February 5, 2020
• Last Update Posted: February 5, 2020