Warm Autoimmune Hemolytic Anemia
Conditions
Brief summary
This main study objective was to evaluate the safety and tolerability of intravenous (IV) SYNT001 (ALXN1830) in participants with WAIHA.
Detailed description
This study planned to evaluate 2 cohorts: Cohort 1, up to 8 participants to receive IV doses of ALXN1830 (SYNT001 Dose 1); Cohort 2, up to 12 participants to receive IV doses of ALXN1830 (SYNT001 Dose 2). This study was terminated after the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy were characterized in participants with WAIHA in Cohort 1 (SYNT001 Dose 1), before any participants were enrolled in Cohort 2.
Interventions
DRUGALXN1830
Administered via IV infusion.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants had to meet the following criteria to be included: * Willing and able to read, understand, and sign an informed consent form * Confirmed diagnosis of WAIHA by enrolling physician * Must have used medically acceptable contraception
Exclusion criteria
Participants who met any of the following criteria were excluded: * Participant 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 or hepatitis C antibody * Positive for hepatitis B surface antigen * Any exposure to an investigational drug or device within the 30 days prior to screening * Intravenous immunoglobulin treatment within 30 days of 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, precluded successful conduct of the study, or interfered with interpretation of the results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Day 0 (after first dose) through Day 112 | A TEAE was defined as any adverse event 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 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 serious TEAEs were not considered related to the study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) On Day 0 And Day 28 | Predose, 5 minutes, 2, 4, 6, 24, and 48 hours, and 5 days postdose | The Cmax was determined directly from the concentration-time profile. Starting on Days 0 and 28, serum samples were collected just prior to the start of study drug infusion (predose), at 5 minutes, at 2, 4, 6, 24, and 48 hours, and at 5 days postdose after the end-of-study drug infusion. Results are reported in micrograms/milliliter (ug/mL). |
| Change From Baseline In Reticulocyte Count At Day 33 | Baseline, Day 33 | Reticulocyte count was measured as a PD biomarker. Pharmacodynamic samples were collected for analyses throughout the study prior to infusion of study drug for Cohort 1. Measurements for PD biomarkers were derived from the laboratory results. Results are reported in cells/liter (cells\*10\^12/L). A decrease in reticulocyte count indicated a potential improvement in condition. |
| Change From Baseline In Hemoglobin At Day 33 | Baseline, Day 33 | Hemoglobin was measured as a PD biomarker. Pharmacodynamic samples were collected for analyses throughout the study prior to infusion of study drug for Cohort 1. Measurements for PD biomarkers were derived from the laboratory results. Results are reported in grams/deciliter (g/dL). An increase in hemoglobin indicated a potential improvement in condition. |
| Immunogenicity Of ALXN1830 At Day 112, As Assessed By Anti-ALXN1830 Antibody Level | Day 112 | Immunogenicity analyses are reported for Day 112. Testing was carried out to detect binding antidrug antibodies by anti-ALXN1830 antibody level. Results are reported as the reciprocal of the titer where they cross the study cut point. |
Countries
Jordan, United States
Participant flow
Pre-assignment details
This study was terminated after the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy were characterized in Cohort 1 (SYNT001 Dose 1), before any participants were enrolled in Cohort 2 (SYNT001 Dose 2). This results disclosure is for Cohort 1 only.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: ALXN1830 SYNT001 Dose 1: Participants received ALXN1830. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Cohort 1: ALXN1830 |
|---|---|
| Age at Warm Autoimmune Hemolytic Anemia Diagnosis | 48.4 years STANDARD_DEVIATION 16.85 |
| Age, Continuous | 54.9 years STANDARD_DEVIATION 16.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 2 / 8 |
Outcome results
Primary
Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs)
A TEAE was defined as any adverse event 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 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 serious TEAEs were not considered related to the study drug.
Time frame: Day 0 (after first dose) through Day 112
Population: Safety Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: ALXN1830 | Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | TEAEs | 8 Participants |
| Cohort 1: ALXN1830 | Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Serious TEAEs | 2 Participants |
| Cohort 1: ALXN1830 | Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Discontinuations due to TEAEs | 0 Participants |
| Cohort 1: ALXN1830 | Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Deaths | 0 Participants |
Secondary
Change From Baseline In Hemoglobin At Day 33
Hemoglobin was measured as a PD biomarker. Pharmacodynamic samples were collected for analyses throughout the study prior to infusion of study drug for Cohort 1. Measurements for PD biomarkers were derived from the laboratory results. Results are reported in grams/deciliter (g/dL). An increase in hemoglobin indicated a potential improvement in condition.
Time frame: Baseline, Day 33
Population: PD Population: All participants who received at least 1dose of study drug and had postdose PD data available at the specified timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: ALXN1830 | Change From Baseline In Hemoglobin At Day 33 | 0.66 g/dL | Standard Deviation 1.581 |
Secondary
Change From Baseline In Reticulocyte Count At Day 33
Reticulocyte count was measured as a PD biomarker. Pharmacodynamic samples were collected for analyses throughout the study prior to infusion of study drug for Cohort 1. Measurements for PD biomarkers were derived from the laboratory results. Results are reported in cells/liter (cells\*10\^12/L). A decrease in reticulocyte count indicated a potential improvement in condition.
Time frame: Baseline, Day 33
Population: PD Population: All participants who received at least 1 dose of study drug and had postdose PD data available at the specified timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: ALXN1830 | Change From Baseline In Reticulocyte Count At Day 33 | -0.044 cells*10^12/L | Standard Deviation 0.0948 |
Secondary
Immunogenicity Of ALXN1830 At Day 112, As Assessed By Anti-ALXN1830 Antibody Level
Immunogenicity analyses are reported for Day 112. Testing was carried out to detect binding antidrug antibodies by anti-ALXN1830 antibody level. Results are reported as the reciprocal of the titer where they cross the study cut point.
Time frame: Day 112
Population: Safety Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: ALXN1830 | Immunogenicity Of ALXN1830 At Day 112, As Assessed By Anti-ALXN1830 Antibody Level | 99.220 reciprocal of the titer | Standard Deviation 165.8149 |
Secondary
Maximum Serum Concentration (Cmax) On Day 0 And Day 28
The Cmax was determined directly from the concentration-time profile. Starting on Days 0 and 28, serum samples were collected just prior to the start of study drug infusion (predose), at 5 minutes, at 2, 4, 6, 24, and 48 hours, and at 5 days postdose after the end-of-study drug infusion. Results are reported in micrograms/milliliter (ug/mL).
Time frame: Predose, 5 minutes, 2, 4, 6, 24, and 48 hours, and 5 days postdose
Population: PK Population: All participants who received at least 1 dose of study drug and had postdose PK data available at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: ALXN1830 | Maximum Serum Concentration (Cmax) On Day 0 And Day 28 | Day 0 | 249.6 ug/mL | Standard Deviation 35.76 |
| Cohort 1: ALXN1830 | Maximum Serum Concentration (Cmax) On Day 0 And Day 28 | Day 28 | 245.8 ug/mL | Standard Deviation 41.55 |