Subcutaneous ALXN1830 in Adult Participants With Warm Autoimmune Hemolytic Anemia

NCT04956276 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: ALXN1830-WAI-202
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Warm Autoimmune Hemolytic Anemia

Keywords

Warm autoimmune hemolytic anemia; WAIHA; Immunoglobulin G-mediated autoimmune disorder; Pathogenesis; Anti-neonatal Fc receptor; ALXN1830

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (24)

• 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

Study Arms (3)

Cohort 1: ALXN1830/Placebo

EXPERIMENTAL

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; Drug: Placebo

Cohort 2: ALXN1830/Placebo

EXPERIMENTAL

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; Drug: Placebo

Cohort 3: ALXN1830

EXPERIMENTAL

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

Interventions

ALXN1830 DRUG

Administered as an SC infusion.

Also known as: SYNT001 (formerly)

Cohort 1: ALXN1830/Placebo; Cohort 2: ALXN1830/Placebo; Cohort 3: ALXN1830

Placebo DRUG

Administered as an SC infusion.

Cohort 1: ALXN1830/Placebo; Cohort 2: ALXN1830/Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (1)

Clinical Study Site

Riverside, California, 90602-3171, United States

Location

MeSH Terms

Interventions

orilanolimab; rhoA GTP-Binding Protein

Intervention Hierarchy (Ancestors)

rho GTP-Binding Proteins; Monomeric GTP-Binding Proteins; GTP-Binding Proteins; GTP Phosphohydrolases; Acid Anhydride Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Intracellular Signaling Peptides and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Cohorts 1 and 2 will be participant and investigator blinded, Cohort 3 will be open label (if initiated).
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2021
• First Posted: July 9, 2021
• Study Start: January 1, 2022
• Primary Completion: July 31, 2022
• Study Completion: July 31, 2024
• Last Updated: February 11, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)