Subcutaneous ALXN1830 in Adult Participants With Warm Autoimmune Hemolytic Anemia

Study Overview
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Brief Summary
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This is a Phase 2, multiple ascending, dose-finding, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, health-related quality of life, tolerability, pharmacokinetic, pharmacodynamic, and immunogenicity, of up to 3 dose regimens of ALXN1830 administered subcutaneous(ly) (SC) in the treatment of WAIHA. This study will include 2 randomized, double-blind, placebo-controlled cohorts (Cohorts 1 and 2) to evaluate an 8-week treatment regimen, and an optional third open-label cohort (Cohort 3) to evaluate an alternative 12-week dosing regimen. Participants may continue participation in this study at the participant's and investigator's discretion in an open-label extension (OLE) period, consisting of monthly visits to observe participants for relapse, which will require going back on active treatment.

Official Title
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A Phase 2, Multiple Ascending Dose, Randomized, Double-Blind, Placebo-Controlled Study of ALXN1830 Administered Subcutaneously 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
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosed with primary or secondary WAIHA at least 6 weeks prior to Screening. Failed or have not tolerated at least one prior WAIHA treatment regimen, for example, corticosteroids, rituximab, azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil, danazol, or vincristine. Hemoglobin < 10 g/dL and ≥ 6 g/dL at Screening. Positive direct antiglobulin test (Coombs) (IgG positive who are positive or negative for the presence of complement C3) at Screening. Evidence of active hemolysis including any one of the below: LDH > upper limit of normal (ULN) or Haptoglobin < lower limit of normal or Indirect bilirubin > ULN Total IgG > 500 mg/dL at Screening Platelet count ≥ 75 x 10^9/liter (L) Absolute neutrophil count greater than 1.0 x 10^9/L Key Exclusion Criteria: Participants with Evan's syndrome. Human immunodeficiency virus (HIV) infection (positive HIV 1 or HIV 2 antibody test). Positive hepatitis B surface antigen or hepatitis C antibody test. Inability to travel to the clinic for specified visits during the Primary Treatment Period or fulfill the logistical requirements of study intervention administration.

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: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: ALXN1830/Placebo<br>Participants will be randomized 3:1 to receive ALXN1830 or placebo. Treatment will be received for 8 weeks followed by a follow-up period (no treatment) for 8 weeks. Once complete, participants may continue participation in the study at the participant's and investigator's discretion during the OLE period for up to 2 years inclusive of primary treatment period. | Drug: ALXN1830<br>* Administered as an SC infusion.<br>* Other names: SYNT001 (formerly);Drug: Placebo<br>* Administered as an SC infusion.<br>|
| Experimental: Cohort 2: ALXN1830/Placebo<br>Participants will be randomized 3:1 to receive ALXN1830 or placebo. Treatment will be received for 8 weeks followed by a follow-up period (no treatment) for 8 weeks. Once complete, participants may continue participation in the study at the participant's and investigator's discretion during the OLE period for up to 2 years inclusive of primary treatment period. | Drug: ALXN1830<br>* Administered as an SC infusion.<br>* Other names: SYNT001 (formerly);Drug: Placebo<br>* Administered as an SC infusion.<br>|
| Experimental: Cohort 3: ALXN1830<br>If initiated, participants will receive ALXN1830. Treatment will be received for 12 weeks followed by a follow-up period (no treatment) for 8 weeks. Once complete, participants may continue participation in the study at the participant's and investigator's discretion during the OLE period for up to 2 years inclusive of primary treatment period. | Drug: ALXN1830<br>* Administered as an SC infusion.<br>* Other names: SYNT001 (formerly);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion Of Participants Achieving A ≥ 2 Grams/Deciliter (g/dL) Increase In Hemoglobin (Hgb) From Baseline To The End Of Primary Treatment | Participants will have to achieve this increase without requiring any increase in the dose of an existing WAIHA medication after Day 1 (baseline) and without packed red blood cells (pRBC) transfusions after Day 14. | Baseline through Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number Of Units Of pRBCs Transfused |  | Baseline through Week 12 | 
| Number Of Hgb Measurements ≥ 2 g/dL From Baseline To The End Of Primary Treatment |  | Baseline, Week 12 | 
| Time To Hgb Increase By ≥ 2 g/dL From Baseline |  | Baseline through Week 12 | 
| Proportion Of Participants Who Require New WAIHA Rescue Medication Or Any Increase In The Dose Of An Existing WAIHA Medication Or pRBC Transfusions For The Treatment Of Anemia |  | Day 15 through Week 12 | 
| Proportion Of Participants Achieving A ≥ 2 g/dL Increase In Hgb From Baseline Through Week 4 | Participants need to achieve this increase without requiring any increase in the dose of an existing WAIHA medication after Day 1 and without pRBC transfusions after Day 14. | Baseline through Week 4 | 
| Change From Baseline To The End Of Primary Treatment In Serum Lactate Dehydrogenase (LDH) Levels |  | Baseline, Week 12 | 
| Change From Baseline To The End Of Primary Treatment In Absolute Reticulocyte Count |  | Baseline, Week 12 | 
| Change From Baseline To The End Of Primary Treatment In Serum Indirect Bilirubin |  | Baseline, Week 12 | 
| Change From Baseline To The End Of Primary Treatment In Serum Haptoglobin |  | Baseline, Week 12 | 
| Total Corticosteroid Usage From Baseline To The End Of Primary Treatment |  | Baseline, Week 12 | 
| Proportion Of Participants Who Require Any Increase In Corticosteroid Dose From Baseline To The End Of Follow Up After Primary Treatment |  | Baseline through Week 20 | 
| Change In Corticosteroid Dose From The End Of Primary Treatment To The End Of Follow Up |  | Week 12, Week 20 | 
| Number Of Days To Beginning Of Corticosteroid Taper During Follow Up After Primary Treatment | Taper is defined as the first day that a lower dose of corticosteroids is prescribed/taken. | Baseline through Week 20 | 
| Number Of Days To Corticosteroid Maintenance Dose During Follow Up After Primary Treatment | Maintenance dose will be defined as < 10 milligrams (mg)/day of prednisone or equivalent. | Baseline through Week 20 | 
| Number Of Days To Reach Corticosteroid Discontinuation From The End Of Primary Treatment To The End Of Follow Up After Primary Treatment |  | Week 12 through Week 20 | 
| Incidence And Titers Of Anti-drug Antibodies Against ALXN1830 Over Time |  | Up to 2 years | 
| Incidence And Titers Of Neutralizing Antibodies Against ALXN1830 Over Time |  | Up to 2 years | 
| Serum Trough Concentrations Of ALXN1830 Over Time |  | Up to 2 years | 
| Change In Serum Total Immunoglobulin G (IgG) Levels By Dose Group And Time Point |  | Up to 2 years | 
| Change From Baseline Of IgG Subtypes (IgG1 4) By Dose Group And Time Point |  | Up to 2 years | 
| Change From Baseline Of IgA By Dose Group And Time Point |  | Up to 2 years | 
| Change From Baseline Of IgM By Dose Group And Time Point |  | Up to 2 years | 
| Change From Baseline Of Albumin By Dose Group And Time Point |  | Up to 2 years | 
| Change From Baseline Of Circulating Immune Complexes By Dose Group And Time Point |  | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Warm autoimmune hemolytic anemia, WAIHA, Immunoglobulin G-mediated autoimmune disorder, Pathogenesis, Anti-neonatal Fc receptor, ALXN1830