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Subcutaneous ALXN1830 in Adult Participants With Warm Autoimmune Hemolytic Anemia

Primary Purpose

Warm Autoimmune Hemolytic Anemia

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ALXN1830
Placebo
Sponsored by
Alexion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Warm Autoimmune Hemolytic Anemia focused on measuring Warm autoimmune hemolytic anemia, WAIHA, Immunoglobulin G-mediated autoimmune disorder, Pathogenesis, Anti-neonatal Fc receptor, ALXN1830

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Clinical Study Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort 1: ALXN1830/Placebo

Cohort 2: ALXN1830/Placebo

Cohort 3: ALXN1830

Arm Description

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.

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.

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.

Outcomes

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
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
Number Of Hgb Measurements ≥ 2 g/dL From Baseline To The End Of Primary Treatment
Time To Hgb Increase By ≥ 2 g/dL From Baseline
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
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.
Change From Baseline To The End Of Primary Treatment In Serum Lactate Dehydrogenase (LDH) Levels
Change From Baseline To The End Of Primary Treatment In Absolute Reticulocyte Count
Change From Baseline To The End Of Primary Treatment In Serum Indirect Bilirubin
Change From Baseline To The End Of Primary Treatment In Serum Haptoglobin
Total Corticosteroid Usage From Baseline To The End Of Primary Treatment
Proportion Of Participants Who Require Any Increase In Corticosteroid Dose From Baseline To The End Of Follow Up After Primary Treatment
Change In Corticosteroid Dose From The End Of Primary Treatment To The End Of Follow Up
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.
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.
Number Of Days To Reach Corticosteroid Discontinuation From The End Of Primary Treatment To The End Of Follow Up After Primary Treatment
Incidence And Titers Of Anti-drug Antibodies Against ALXN1830 Over Time
Incidence And Titers Of Neutralizing Antibodies Against ALXN1830 Over Time
Serum Trough Concentrations Of ALXN1830 Over Time
Change In Serum Total Immunoglobulin G (IgG) Levels By Dose Group And Time Point
Change From Baseline Of IgG Subtypes (IgG1 4) By Dose Group And Time Point
Change From Baseline Of IgA By Dose Group And Time Point
Change From Baseline Of IgM By Dose Group And Time Point
Change From Baseline Of Albumin By Dose Group And Time Point
Change From Baseline Of Circulating Immune Complexes By Dose Group And Time Point

Full Information

First Posted
June 30, 2021
Last Updated
February 2, 2022
Sponsor
Alexion
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1. Study Identification

Unique Protocol Identification Number
NCT04956276
Brief Title
Subcutaneous ALXN1830 in Adult Participants With Warm Autoimmune Hemolytic Anemia
Official Title
A Phase 2, Multiple Ascending Dose, Randomized, Double-Blind, Placebo-Controlled Study of ALXN1830 Administered Subcutaneously in Patients With Warm Autoimmune Hemolytic Anemia (WAIHA)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Sponsor decision to terminate program
Study Start Date
January 1, 2022 (Anticipated)
Primary Completion Date
July 31, 2022 (Anticipated)
Study Completion Date
July 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Warm Autoimmune Hemolytic Anemia
Keywords
Warm autoimmune hemolytic anemia, WAIHA, Immunoglobulin G-mediated autoimmune disorder, Pathogenesis, Anti-neonatal Fc receptor, ALXN1830

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Masking Description
Cohorts 1 and 2 will be participant and investigator blinded, Cohort 3 will be open label (if initiated).
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: ALXN1830/Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2: ALXN1830/Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 3: ALXN1830
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ALXN1830
Other Intervention Name(s)
SYNT001 (formerly)
Intervention Description
Administered as an SC infusion.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered as an SC infusion.
Primary Outcome Measure Information:
Title
Proportion Of Participants Achieving A ≥ 2 Grams/Deciliter (g/dL) Increase In Hemoglobin (Hgb) From Baseline To The End Of Primary Treatment
Description
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.
Time Frame
Baseline through Week 12
Secondary Outcome Measure Information:
Title
Total Number Of Units Of pRBCs Transfused
Time Frame
Baseline through Week 12
Title
Number Of Hgb Measurements ≥ 2 g/dL From Baseline To The End Of Primary Treatment
Time Frame
Baseline, Week 12
Title
Time To Hgb Increase By ≥ 2 g/dL From Baseline
Time Frame
Baseline through Week 12
Title
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
Time Frame
Day 15 through Week 12
Title
Proportion Of Participants Achieving A ≥ 2 g/dL Increase In Hgb From Baseline Through Week 4
Description
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.
Time Frame
Baseline through Week 4
Title
Change From Baseline To The End Of Primary Treatment In Serum Lactate Dehydrogenase (LDH) Levels
Time Frame
Baseline, Week 12
Title
Change From Baseline To The End Of Primary Treatment In Absolute Reticulocyte Count
Time Frame
Baseline, Week 12
Title
Change From Baseline To The End Of Primary Treatment In Serum Indirect Bilirubin
Time Frame
Baseline, Week 12
Title
Change From Baseline To The End Of Primary Treatment In Serum Haptoglobin
Time Frame
Baseline, Week 12
Title
Total Corticosteroid Usage From Baseline To The End Of Primary Treatment
Time Frame
Baseline, Week 12
Title
Proportion Of Participants Who Require Any Increase In Corticosteroid Dose From Baseline To The End Of Follow Up After Primary Treatment
Time Frame
Baseline through Week 20
Title
Change In Corticosteroid Dose From The End Of Primary Treatment To The End Of Follow Up
Time Frame
Week 12, Week 20
Title
Number Of Days To Beginning Of Corticosteroid Taper During Follow Up After Primary Treatment
Description
Taper is defined as the first day that a lower dose of corticosteroids is prescribed/taken.
Time Frame
Baseline through Week 20
Title
Number Of Days To Corticosteroid Maintenance Dose During Follow Up After Primary Treatment
Description
Maintenance dose will be defined as < 10 milligrams (mg)/day of prednisone or equivalent.
Time Frame
Baseline through Week 20
Title
Number Of Days To Reach Corticosteroid Discontinuation From The End Of Primary Treatment To The End Of Follow Up After Primary Treatment
Time Frame
Week 12 through Week 20
Title
Incidence And Titers Of Anti-drug Antibodies Against ALXN1830 Over Time
Time Frame
Up to 2 years
Title
Incidence And Titers Of Neutralizing Antibodies Against ALXN1830 Over Time
Time Frame
Up to 2 years
Title
Serum Trough Concentrations Of ALXN1830 Over Time
Time Frame
Up to 2 years
Title
Change In Serum Total Immunoglobulin G (IgG) Levels By Dose Group And Time Point
Time Frame
Up to 2 years
Title
Change From Baseline Of IgG Subtypes (IgG1 4) By Dose Group And Time Point
Time Frame
Up to 2 years
Title
Change From Baseline Of IgA By Dose Group And Time Point
Time Frame
Up to 2 years
Title
Change From Baseline Of IgM By Dose Group And Time Point
Time Frame
Up to 2 years
Title
Change From Baseline Of Albumin By Dose Group And Time Point
Time Frame
Up to 2 years
Title
Change From Baseline Of Circulating Immune Complexes By Dose Group And Time Point
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Clinical Study Site
City
Riverside
State/Province
California
ZIP/Postal Code
90602-3171
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

Subcutaneous ALXN1830 in Adult Participants With Warm Autoimmune Hemolytic Anemia

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