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Sponsor decision to terminate program
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: ALXN1830/Placebo | Experimental | 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. |
|
| Cohort 2: ALXN1830/Placebo | Experimental | 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. |
|
| Cohort 3: ALXN1830 | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ALXN1830 | Drug | Administered as an SC infusion. |
|
| 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 |
| 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 | |
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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:
Key Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Study Site | Riverside | California | 90602-3171 | United States |
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| ID | Term |
|---|---|
| C000708950 | orilanolimab |
| D020742 | rhoA GTP-Binding Protein |
| ID | Term |
|---|---|
| D020741 | rho GTP-Binding Proteins |
| D020559 | Monomeric GTP-Binding Proteins |
| D019204 | GTP-Binding Proteins |
| D020558 | GTP Phosphohydrolases |
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Cohorts 1 and 2 will be participant and investigator blinded, Cohort 3 will be open label (if initiated).
| Placebo | Drug | Administered as an SC infusion. |
|
| 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 |
| D017766 | Acid Anhydride Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D002352 | Carrier Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D047908 | Intracellular Signaling Peptides and Proteins |