Subcutaneous ALXN1830 in Adult Participants With Warm Autoimmune Hemolytic Anemia

A Phase 2, Multiple Ascending Dose, Randomized, Double-Blind, Placebo-Controlled Study of ALXN1830 Administered Subcutaneously in Patients With Warm Autoimmune Hemolytic Anemia (WAIHA)

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.

Study Overview

• Status: Withdrawn
• Conditions: Warm Autoimmune Hemolytic Anemia
• Intervention / Treatment: Drug: ALXN1830; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Riverside, California, United States, 90602-3171
      • Clinical Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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: SYNT001 (formerly); 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: SYNT001 (formerly); 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: SYNT001 (formerly)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alexion

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): July 31, 2022
• Study Completion (Anticipated): July 31, 2024

Study Registration Dates

• First Submitted: June 30, 2021
• First Submitted That Met QC Criteria: June 30, 2021
• First Posted (Actual): July 9, 2021

Study Record Updates

• Last Update Posted (Actual): February 11, 2022
• Last Update Submitted That Met QC Criteria: February 2, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Pathogenesis; WAIHA; ALXN1830; Warm autoimmune hemolytic anemia; Immunoglobulin G-mediated autoimmune disorder; Anti-neonatal Fc receptor
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: ALXN1830-WAI-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No