Clinical trial NCT04956276: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Warm Autoimmune Hemolytic Anemia
Keywords: Warm autoimmune hemolytic anemia
WAIHA
Immunoglobulin G-mediated autoimmune disorder
Pathogenesis
Anti-neonatal Fc receptor
ALXN1830
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-07-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Proportion Of Participants Achieving A ≥ 2 Grams/Deciliter (g/dL) Increase In Hemoglobin (Hgb) From Baseline To The End Of Primary Treatment
timeFrame: Baseline through Week 12
Secondary outcomes:
measure: Total Number Of Units Of pRBCs Transfused
timeFrame: Baseline through Week 12
measure: Number Of Hgb Measurements ≥ 2 g/dL From Baseline To The End Of Primary Treatment
timeFrame: Baseline, Week 12
measure: Time To Hgb Increase By ≥ 2 g/dL From Baseline
timeFrame: Baseline through Week 12
measure: 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
timeFrame: Day 15 through Week 12
measure: Proportion Of Participants Achieving A ≥ 2 g/dL Increase In Hgb From Baseline Through Week 4
timeFrame: Baseline through Week 4
measure: Change From Baseline To The End Of Primary Treatment In Serum Lactate Dehydrogenase (LDH) Levels
timeFrame: Baseline, Week 12
measure: Change From Baseline To The End Of Primary Treatment In Absolute Reticulocyte Count
timeFrame: Baseline, Week 12
measure: Change From Baseline To The End Of Primary Treatment In Serum Indirect Bilirubin
timeFrame: Baseline, Week 12
measure: Change From Baseline To The End Of Primary Treatment In Serum Haptoglobin
timeFrame: Baseline, Week 12
measure: Total Corticosteroid Usage From Baseline To The End Of Primary Treatment
timeFrame: Baseline, Week 12
measure: Proportion Of Participants Who Require Any Increase In Corticosteroid Dose From Baseline To The End Of Follow Up After Primary Treatment
timeFrame: Baseline through Week 20
measure: Change In Corticosteroid Dose From The End Of Primary Treatment To The End Of Follow Up
timeFrame: Week 12, Week 20
measure: Number Of Days To Beginning Of Corticosteroid Taper During Follow Up After Primary Treatment
timeFrame: Baseline through Week 20
measure: Number Of Days To Corticosteroid Maintenance Dose During Follow Up After Primary Treatment
timeFrame: Baseline through Week 20
measure: Number Of Days To Reach Corticosteroid Discontinuation From The End Of Primary Treatment To The End Of Follow Up After Primary Treatment
timeFrame: Week 12 through Week 20
measure: Incidence And Titers Of Anti-drug Antibodies Against ALXN1830 Over Time
timeFrame: Up to 2 years
measure: Incidence And Titers Of Neutralizing Antibodies Against ALXN1830 Over Time
timeFrame: Up to 2 years
measure: Serum Trough Concentrations Of ALXN1830 Over Time
timeFrame: Up to 2 years
measure: Change In Serum Total Immunoglobulin G (IgG) Levels By Dose Group And Time Point
timeFrame: Up to 2 years
measure: Change From Baseline Of IgG Subtypes (IgG1 4) By Dose Group And Time Point
timeFrame: Up to 2 years
measure: Change From Baseline Of IgA By Dose Group And Time Point
timeFrame: Up to 2 years
measure: Change From Baseline Of IgM By Dose Group And Time Point
timeFrame: Up to 2 years
measure: Change From Baseline Of Albumin By Dose Group And Time Point
timeFrame: Up to 2 years
measure: Change From Baseline Of Circulating Immune Complexes By Dose Group And Time Point
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Riverside
country: United States
facility: Clinical Study Site
state: California
Study officials:
References: