Warm Autoimmune Hemolytic Anemia
Conditions
Keywords
Warm autoimmune hemolytic anemia, WAIHA, Immunoglobulin G-mediated autoimmune disorder, Pathogenesis, Anti-neonatal Fc receptor, ALXN1830
Brief summary
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.
Interventions
DRUGALXN1830
Administered as an SC infusion.
DRUGPlacebo
Administered as an SC infusion.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Cohorts 1 and 2 will be participant and investigator blinded, Cohort 3 will be open label (if initiated).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion Of Participants Achieving A ≥ 2 Grams/Deciliter (g/dL) Increase In Hemoglobin (Hgb) From Baseline To The End Of Primary Treatment | Baseline through Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | — |
| Total Number Of Units Of pRBCs Transfused | Baseline through Week 12 | — |
| Number Of Days To Corticosteroid Maintenance Dose During Follow Up After Primary Treatment | Baseline through Week 20 | Maintenance dose will be defined as \< 10 milligrams (mg)/day of prednisone or equivalent. |
| 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 | — |
| Number Of Days To Beginning Of Corticosteroid Taper During Follow Up After Primary Treatment | Baseline through Week 20 | Taper is defined as the first day that a lower dose of corticosteroids is prescribed/taken. |
Countries
United States
Outcome results
None listed