A Safety Study of SYNT001 in Participants With Warm Autoimmune Hemolytic Anemia (WAIHA)

Study Overview
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Brief Summary
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This main study objective was to evaluate the safety and tolerability of intravenous (IV) SYNT001 (ALXN1830) in participants with WAIHA.

Detailed Description
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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.

Official Title
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A Phase 1B/2, Multicenter, Open-Label, Safety, Tolerability, and Activity Study of SYNT001 in Patients With Warm Autoimmune Hemolytic Anemia (WAIHA)

Conditions
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Warm Autoimmune Hemolytic Anemia

Intervention / Treatment
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* Drug: ALXN1830


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: ALXN1830<br>SYNT001 Dose 1 | Drug: ALXN1830<br>* Administered via IV infusion.<br>* Other names: SYNT001;|
| Experimental: Cohort 2: ALXN1830<br>SYNT001 Dose 2 | Drug: ALXN1830<br>* Administered via IV infusion.<br>* Other names: SYNT001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 0 (after first dose) through Day 112 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Predose, 5 minutes, 2, 4, 6, 24, and 48 hours, and 5 days postdose | 
| 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. | Baseline, Day 33 | 
| 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. | Baseline, Day 33 | 
| 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. | Day 112 |