Subcutaneous ALXN1830 in Adult Participants With Warm Autoimmune Hemolytic Anemia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1: ALXN1830/Placebo 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
Administered as an SC infusion.
Other Names:
Drug: Placebo
Administered as an SC infusion.
|
| Experimental: Cohort 2: ALXN1830/Placebo 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
Administered as an SC infusion.
Other Names:
Drug: Placebo
Administered as an SC infusion.
|
| Experimental: Cohort 3: ALXN1830 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
Administered as an SC infusion.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 [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]
- 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.
- 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]
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Study Site | Riverside | California | United States | 90602-3171 |
Sponsors and Collaborators
- Alexion Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ALXN1830-WAI-202