A Safety Study of SYNT001 in Participants With Warm Autoimmune Hemolytic Anemia (WAIHA)
Study Details
Study Description
Brief Summary
This main study objective was to evaluate the safety and tolerability of intravenous (IV) SYNT001 (ALXN1830) in participants with WAIHA.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Cohort 1: ALXN1830 SYNT001 Dose 1 |
Drug: ALXN1830
Administered via IV infusion.
Other Names:
|
Experimental: Cohort 2: ALXN1830 SYNT001 Dose 2 |
Drug: ALXN1830
Administered via IV infusion.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Alexion Study Site | Los Angeles | California | United States | 90033 |
2 | Alexion Study Site | San Francisco | California | United States | 94143 |
3 | Alexion Study Site | Boston | Massachusetts | United States | 02114 |
4 | Alexion Study Site | Pittsfield | Massachusetts | United States | 01201 |
5 | Alexion Study Site | Rochester | Minnesota | United States | 55905 |
6 | Alexion Study Site | Cleveland | Ohio | United States | 44106 |
7 | Alexion Study Site | Philadelphia | Pennsylvania | United States | 19104 |
8 | Alexion Study Site | Pittsburgh | Pennsylvania | United States | 15232 |
9 | Alexion Study Site | Seattle | Washington | United States | 98195 |
10 | Alexion Study Site | Amman | Jordan | 11941 |
Sponsors and Collaborators
- Alexion Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- SYNT001-102
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | 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. |
Arm/Group Title | Cohort 1: ALXN1830 |
---|---|
Arm/Group Description | SYNT001 Dose 1: Participants received ALXN1830. |
Period Title: Overall Study | |
STARTED | 8 |
Received at Least 1 Dose of Study Drug | 8 |
COMPLETED | 7 |
NOT COMPLETED | 1 |
Baseline Characteristics
Arm/Group Title | Cohort 1: ALXN1830 |
---|---|
Arm/Group Description | SYNT001 Dose 1: Participants received ALXN1830. |
Overall Participants | 8 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
54.9
(16.82)
|
Sex: Female, Male (Count of Participants) | |
Female |
6
75%
|
Male |
2
25%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
2
25%
|
Not Hispanic or Latino |
6
75%
|
Unknown or Not Reported |
0
0%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
1
12.5%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
1
12.5%
|
White |
6
75%
|
More than one race |
0
0%
|
Unknown or Not Reported |
0
0%
|
Age at Warm Autoimmune Hemolytic Anemia Diagnosis (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
48.4
(16.85)
|
Outcome Measures
Title | Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population: All participants who received at least 1 dose of study drug. |
Arm/Group Title | Cohort 1: ALXN1830 |
---|---|
Arm/Group Description | SYNT001 Dose 1: Participants received ALXN1830. |
Measure Participants | 8 |
TEAEs |
8
100%
|
Serious TEAEs |
2
25%
|
Discontinuations due to TEAEs |
0
0%
|
Deaths |
0
0%
|
Title | Maximum Serum Concentration (Cmax) On Day 0 And Day 28 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
PK Population: All participants who received at least 1 dose of study drug and had postdose PK data available at the specified timepoint. |
Arm/Group Title | Cohort 1: ALXN1830 |
---|---|
Arm/Group Description | SYNT001 Dose 1: Participants received ALXN1830. |
Measure Participants | 8 |
Day 0 |
249.6
(35.76)
|
Day 28 |
245.8
(41.55)
|
Title | Change From Baseline In Reticulocyte Count At Day 33 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
PD Population: All participants who received at least 1 dose of study drug and had postdose PD data available at the specified timepoint. |
Arm/Group Title | Cohort 1: ALXN1830 |
---|---|
Arm/Group Description | SYNT001 Dose 1: Participants received ALXN1830. |
Measure Participants | 7 |
Mean (Standard Deviation) [cells*10^12/L] |
-0.044
(0.0948)
|
Title | Change From Baseline In Hemoglobin At Day 33 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
PD Population: All participants who received at least 1dose of study drug and had postdose PD data available at the specified timepoint. |
Arm/Group Title | Cohort 1: ALXN1830 |
---|---|
Arm/Group Description | SYNT001 Dose 1: Participants received ALXN1830. |
Measure Participants | 8 |
Mean (Standard Deviation) [g/dL] |
0.66
(1.581)
|
Title | Immunogenicity Of ALXN1830 At Day 112, As Assessed By Anti-ALXN1830 Antibody Level |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population: All participants who received at least 1 dose of study drug. |
Arm/Group Title | Cohort 1: ALXN1830 |
---|---|
Arm/Group Description | SYNT001 Dose 1: Participants received ALXN1830. |
Measure Participants | 4 |
Mean (Standard Deviation) [reciprocal of the titer] |
99.220
(165.8149)
|
Adverse Events
Time Frame | Baseline through Day 112 | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Cohort 1: ALXN1830 | |
Arm/Group Description | SYNT001 Dose 1: Participants received ALXN1830. | |
All Cause Mortality |
||
Cohort 1: ALXN1830 | ||
Affected / at Risk (%) | # Events | |
Total | 0/8 (0%) | |
Serious Adverse Events |
||
Cohort 1: ALXN1830 | ||
Affected / at Risk (%) | # Events | |
Total | 2/8 (25%) | |
Blood and lymphatic system disorders | ||
Anaemia | 1/8 (12.5%) | |
Gastrointestinal disorders | ||
Gastritis | 1/8 (12.5%) | |
Other (Not Including Serious) Adverse Events |
||
Cohort 1: ALXN1830 | ||
Affected / at Risk (%) | # Events | |
Total | 8/8 (100%) | |
Blood and lymphatic system disorders | ||
Anaemia | 1/8 (12.5%) | |
Thrombocytopenia | 1/8 (12.5%) | |
Cardiac disorders | ||
Sinus tachycardia | 2/8 (25%) | |
Eye disorders | ||
Blepharospasm | 1/8 (12.5%) | |
Gastrointestinal disorders | ||
Constipation | 2/8 (25%) | |
Nausea | 2/8 (25%) | |
Abdominal pain | 1/8 (12.5%) | |
General disorders | ||
Fatigue | 2/8 (25%) | |
Chills | 1/8 (12.5%) | |
Face oedema | 1/8 (12.5%) | |
Influenza like illness | 1/8 (12.5%) | |
Oedema peripheral | 1/8 (12.5%) | |
Pyrexia | 1/8 (12.5%) | |
Infections and infestations | ||
Pneumonia | 1/8 (12.5%) | |
Rhinitis | 1/8 (12.5%) | |
Upper respiratory tract infection | 1/8 (12.5%) | |
Urinary tract infection | 1/8 (12.5%) | |
Injury, poisoning and procedural complications | ||
Fall | 1/8 (12.5%) | |
Infusion-related reaction | 1/8 (12.5%) | |
Limb injury | 1/8 (12.5%) | |
Post-traumatic pain | 1/8 (12.5%) | |
Investigations | ||
Haematocrit decreased | 1/8 (12.5%) | |
Haemoglobin decreased | 1/8 (12.5%) | |
Metabolism and nutrition disorders | ||
Increased appetite | 1/8 (12.5%) | |
Musculoskeletal and connective tissue disorders | ||
Back pain | 1/8 (12.5%) | |
Muscle spasms | 1/8 (12.5%) | |
Nervous system disorders | ||
Headache | 4/8 (50%) | |
Dizziness | 2/8 (25%) | |
Dizziness postural | 1/8 (12.5%) | |
Hypersomnia | 1/8 (12.5%) | |
Syncope | 1/8 (12.5%) | |
Psychiatric disorders | ||
Restlessness | 1/8 (12.5%) | |
Respiratory, thoracic and mediastinal disorders | ||
Dyspnoea | 2/8 (25%) | |
Cough | 1/8 (12.5%) | |
Dyspnoea exertional | 1/8 (12.5%) | |
Skin and subcutaneous tissue disorders | ||
Dermatitis contact | 1/8 (12.5%) | |
Hyperhidrosis | 1/8 (12.5%) | |
Rash maculo-papular | 1/8 (12.5%) | |
Rash pruritic | 1/8 (12.5%) | |
Vascular disorders | ||
Flushing | 1/8 (12.5%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor can review results communications at least 60 days prior to public release. Within 30 days of receipt, Sponsor shall advise of any information which is Confidential Information (other than Study Data) or which may impair the availability of patent protection for Inventions. Sponsor can require removal of specifically identified Confidential Information (other than Study Data) and/or delay the communication an additional 60 days to enable Sponsor to seek patent protection for Inventions.
Results Point of Contact
Name/Title | Alexion Pharmaceuticals, Inc. |
---|---|
Organization | Alexion Pharmaceuticals, Inc. |
Phone | 855-752-2356 |
clinicaltrials@alexion.com |
- SYNT001-102