Not provided
Not provided
Not provided
Not provided
Not provided
Study objectives achieved
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: ALXN1830 | Experimental | Participants received 5 doses of ALXN1830 10 mg/kg administered weekly. |
|
| Cohort 2: ALXN1830 | Experimental | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ALXN1830 | Drug | Administered via IV infusion. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1 (after first dose) through Day 112 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline through Day 112 |
| Maximum Percent Reduction In Mean Pemphigus Disease Area Index (PDAI) Total Activity Score From Baseline |
Not provided
Inclusion Criteria:
Participants must have meet the following criteria to be included:
Exclusion Criteria:
Participants meeting any of the following criteria were excluded:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alexion Study Site | Chapel Hill | North Carolina | 27516 | United States | ||
| Alexion Study Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34126109 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: ALXN1830 | Participants received 5 doses of ALXN1830 10 mg/kg administered weekly. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All participants who were enrolled in the study.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: ALXN1830 | Participants received 5 doses of ALXN1830 10 mg/kg administered weekly. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | All participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Day 1 (after first dose) through Day 112 |
Baseline through Day 112
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: ALXN1830 | Participants received 5 doses of ALXN1830 10 mg/kg administered weekly. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Disease progression | General disorders | MedDRA 19.1 | Systematic Assessment | Resolved and was considered to be not related to the study drug by the Investigator. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dry eye | Eye disorders | MedDRA 19.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alexion Pharmaceuticals, Inc. | Alexion Pharmaceuticals, Inc. | 855-752-2356 | clinicaltrials@alexion.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 25, 2019 | Jan 15, 2020 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Sep 18, 2018 | Jan 16, 2020 | Prot_001.pdf |
Not provided
| ID | Term |
|---|---|
| D010392 | Pemphigus |
| ID | Term |
|---|---|
| D012872 | Skin Diseases, Vesiculobullous |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000708950 | orilanolimab |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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. |
| Baseline through Day 112 |
| 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. | Baseline through Day 112 |
| 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. | Baseline through Day 112 |
| Durham |
| North Carolina |
| 27710 |
| United States |
| Alexion Study Site | Philadelphia | Pennsylvania | 19104 | United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type of Pemphigus | Count of Participants | Participants |
|
| Age at Diagnosis of Pemphigus | Mean | Standard Deviation | years |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Cohort 1: ALXN1830 | Participants received 5 doses of ALXN1830 10 mg/kg administered weekly. |
|
|
| Secondary | 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. | All participants who received at least 1 dose of study drug and had postdose pharmacodynamic data available. | Posted | Number | percentage of reduction | Baseline through Day 112 |
|
|
|
| Secondary | 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. | All participants who received at least 1 dose of study drug and had postdose pharmacodynamic data available. | Posted | Number | percentage of reduction | Baseline through Day 112 |
|
|
|
| Secondary | 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. | All participants who received at least 1 dose of study drug and had postdose pharmacodynamic data available. | Posted | Number | percentage of reduction | Baseline through Day 112 |
|
|
|
| Secondary | 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. | All participants who received at least 1 dose of study drug and had postdose pharmacodynamic data available. | Posted | Number | percentage of reduction | Baseline through Day 112 |
|
|
|
| 0 |
| 8 |
| 1 |
| 8 |
| 7 |
| 8 |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 19.1 | Systematic Assessment | Resolved and was considered to be not related to the study drug by the Investigator. |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 19.1 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 19.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 19.1 | Systematic Assessment |
|
| Hepatic cyst | Hepatobiliary disorders | MedDRA 19.1 | Systematic Assessment |
|
| Herpes simplex | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
|
| Staphylococcal infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
|
| Tinea barbae | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
|
| Urine analysis abnormal | Investigations | MedDRA 19.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
|
| Sinus headache | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 19.1 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
|
| Pallor | Vascular disorders | MedDRA 19.1 | Systematic Assessment |
|
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.
| D007154 | Immune System Diseases |