Subcutaneous ALXN1830 in Adult Participants With Warm Autoimmune Hemolytic Anemia

Warm Autoimmune Hemolytic Anemia Clinical Trial

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)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04956276
• Other study ID #: ALXN1830-WAI-202
• Status: Withdrawn
• Phase: Phase 2
• Start date: January 1, 2022
• Est. completion date: July 31, 2024

Study information

• Verified date: February 2022
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 31, 2024
• Est. primary completion date: July 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia, Hemolytic
• Anemia, Hemolytic, Autoimmune
• Hemolysis
• Warm Autoimmune Hemolytic Anemia

Intervention

Drug:
• ALXN1830
Administered as an SC infusion.
• Placebo
Administered as an SC infusion.

Locations

Country	Name	City	State
United States	Clinical Study Site	Riverside	California

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Total Number Of Units Of pRBCs Transfused		Baseline through Week 12
Secondary	Number Of Hgb Measurements = 2 g/dL From Baseline To The End Of Primary Treatment		Baseline, Week 12
Secondary	Time To Hgb Increase By = 2 g/dL From Baseline		Baseline through Week 12
Secondary	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
Secondary	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
Secondary	Change From Baseline To The End Of Primary Treatment In Serum Lactate Dehydrogenase (LDH) Levels		Baseline, Week 12
Secondary	Change From Baseline To The End Of Primary Treatment In Absolute Reticulocyte Count		Baseline, Week 12
Secondary	Change From Baseline To The End Of Primary Treatment In Serum Indirect Bilirubin		Baseline, Week 12
Secondary	Change From Baseline To The End Of Primary Treatment In Serum Haptoglobin		Baseline, Week 12
Secondary	Total Corticosteroid Usage From Baseline To The End Of Primary Treatment		Baseline, Week 12
Secondary	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
Secondary	Change In Corticosteroid Dose From The End Of Primary Treatment To The End Of Follow Up		Week 12, Week 20
Secondary	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
Secondary	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
Secondary	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
Secondary	Incidence And Titers Of Anti-drug Antibodies Against ALXN1830 Over Time		Up to 2 years
Secondary	Incidence And Titers Of Neutralizing Antibodies Against ALXN1830 Over Time		Up to 2 years
Secondary	Serum Trough Concentrations Of ALXN1830 Over Time		Up to 2 years
Secondary	Change In Serum Total Immunoglobulin G (IgG) Levels By Dose Group And Time Point		Up to 2 years
Secondary	Change From Baseline Of IgG Subtypes (IgG1 4) By Dose Group And Time Point		Up to 2 years
Secondary	Change From Baseline Of IgA By Dose Group And Time Point		Up to 2 years
Secondary	Change From Baseline Of IgM By Dose Group And Time Point		Up to 2 years
Secondary	Change From Baseline Of Albumin By Dose Group And Time Point		Up to 2 years
Secondary	Change From Baseline Of Circulating Immune Complexes By Dose Group And Time Point		Up to 2 years