Hypoxic Red Blood Cells in Sickle Cell Anemia

A Multi-Center, Randomized, Controlled, Cross-Over Study to Evaluate the Effectiveness of Hypoxic Red Blood Cells Processed With the Hemanext ONE® System Versus Conventional Red Blood Cells in Patients With Transfusion Dependent Sickle Cell Anemia

The overall objective of this study is to evaluate the effectiveness and safety of transfusing hypoxic red blood cells manufactured with the Hemanext ONE system in patients with sickle cell anemia. The Hemanext ONE device was cleared through the De Novo process in September 2023.

Study Overview

• Status: Not yet recruiting
• Conditions: Sickle Cell Anemia in Children; Sickle Cell Anaemia; Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0); Sickle Cell Anemia Crisis
• Intervention / Treatment: Device: Hemanext ONE System; Device: Conventional RBCs

Detailed Description

In this Direct-to-Phase II study, Hemanext Inc. will carry out a prospective, multi-center, single-blind, randomized, cross-over study in patients with Sickle Cell Anemia, comparing the efficacy of transfusion of hypoxic red blood cells (HRBCs) to transfusions with conventional RBCs. The primary efficacy objective is to demonstrate an increase in %HbA between red cell exchange transfusions (RCE) of HRBCs compared to conventional RBCs. The increases in %HbA (normal Hb) from RCE will be accompanied by a concomitant decrease in sickle Hb (%HbS). The persistence of %HbA will allow for a decrease in the volume of RBCs transfused with an overall decrease in the number of units consumed, which in turn can result in an increase in time (number of days) between transfusions.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jill Bagdasarian; Phone Number: (781) 301-7474; Email: jill.bagdasarian@hemanext.com

Study Locations

• United States
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • New England Sickle Cell Institute, University of Connecticut
      • Principal Investigator: Biree Andemariam, MD
      • Contact: Biree Andemariam, MD; Phone Number: 860-679-2100; Email: andemariam@uchc.edu
  • Florida
    • St. Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital
      • Principal Investigator: Cassandra Josephson, MD
      • Contact: Cassandra Josephson, MD; Phone Number: 727-767-8884; Email: cjosep22@jhmi.edu
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
      • Contact: Ross Fasano, MD; Phone Number: 404-727-5910; Email: ross.fasano@emory.edu
      • Principal Investigator: Ross Fasano, MD
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins University School of Medicine
      • Contact: Elizabeth Crowe, MD, PhD; Phone Number: 443-287-6854; Email: ecrowe3@jhmi.edu
      • Principal Investigator: Elizabeth Crowe, MD, PhD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
      • Contact: Alesia Kaplan, MD; Phone Number: 412-209-7238; Email: kaplana@upmc.edu
      • Principal Investigator: Alesia Kaplan, MD
    • Pittsburgh, Pennsylvania, United States, 15260
      • University of Pittsburgh Medical Center
      • Contact: Enrico Novelli, MD, MS; Phone Number: 412-624-2591; Email: novellie@upmc.edu
      • Principal Investigator: Enrico Novelli, MD, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female at least 7 years of age;
2. Are able to provide informed consent, and assent as applicable, to participate in the study;
3. Diagnosis of Sickle Cell Anemia (SCA) (HbSS, HbSβ0 thalassemia) with participation in a chronic transfusion program and have undergone regular transfusions during at least 6 months prior to Screening;
4. Have had an average interval of at least 14 days between RBC transfusions over the past 6 months;
5. If on iron chelation therapy, have been on a stable dose for ≥3 months prior to screening;

Exclusion Criteria:

1. Are not exclusively transfused at the site;
2. Have a diagnosis of HbSC disease, HbSβ+ thalassemia or another SCD variant (excluding HbSS and HbSβ0 thalassemia)
3. Are routinely transfused with washed, packed RBC units;
4. Have received hemoglobin inducers (e.g. erythropoietin) in the 30 days prior to Screening;
5. Are currently being evaluated for gene therapy;
6. Have any clinically significant pulmonary, cardiovascular, endocrine, hepatic, gastrointestinal, renal, infectious, immunological (including significant allo- or auto-immunization) disease, considered not adequately controlled prior to the study;
7. Are a female of child-bearing potential who is pregnant or planning to become pregnant in the next 14 months;
8. Have a history of allo-immunization that cannot be managed by the local blood bank;
9. Patients who, in the opinion of the Investigator, would not be able or willing to comply with the protocol;
10. Is a ward of the state, prisoner, or transient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A (Hypoxic RBCs); Transfusion of hypoxic red blood cells manufactured with Hemanext ONE system	Device: Hemanext ONE System; Hypoxic red blood cells
Active Comparator: Treatment B (Conventional RBCs); Transfusion of conventional red blood cells	Device: Conventional RBCs; Conventional red blood cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
%HbA Rate of Decline	The primary objective is to evaluate the decreased rate of decline of %HbA between post-transfusion RCE and the subsequent pre-transfusion RCE over 6 transfusion cycles in the hypoxic RBC group compared to the conventional group.	Through study completion, an average of 14 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volume of blood transfused	The mean volume of blood per patient transfused with hypoxic RBCs and with standard RBC units will be analyzed and compared	Through study completion, an average of 14 months
HgbS Rate of Increase	Average rate of increase of the HgbS measurement between automated red cell exchange (RCE) of hypoxic RBCs compared to conventional RBCs.	Through study completion, an average of 14 months
Incidence rate of vaso-occlusive crisis.	Incidence rate of vaso-occlusive crisis events through the duration of the study	Through study completion, an average of 14 months
Incidence rate of acute chest syndrome	Incidence rate of acute chest syndrome events accompanied by fever and/or respiratory symptoms through the duration of the study	Through study completion, an average of 14 months
Duration (days) of any hospitalization for vaso-occlusive crisis	Mean duration (days) of any hospitalization for vaso-occlusive crisis	Through study completion, an average of 14 months
Intravascular hemolysis	Level of intravascular hemolysis (measured with free plasma hemoglobin) between each procedure, before and after each Red Cell Exchange.	Through study completion, an average of 14 months
Serum ferritin	Mean change from baseline in serum ferritin	Through study completion, an average of 14 months
Changes in hepatic iron content	Mean changes in hepatic iron content	Through study completion, an average of 14 months
Change in QoL	Mean change in QoL, as measured by validated QoL questionnaires	Through study completion, an average of 14 months
Total hemoglobin before and after RCE	Mean change before and after transfusions of hypoxically stored RBCs compared to that with conventionally stored RBCs.	Through study completion, an average of 14 months
Total hematocrit before and after RCE	Mean change before and after transfusions of hypoxically stored RBCs compared to that with conventionally stored RBCs.	Through study completion, an average of 14 months
Red Cell Exchange events	Mean number of RCE events over the course of the study	Through study completion, an average of 14 months
Safety assessment	Frequency of adverse event reactions and device deficiencies over the course of the study	Through study completion, an average of 14 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin increment from each transfusion	The hemoglobin increment from each transfusion will be determined by calculating the difference between the patient's post-transfusion and pre-transfusion hemoglobin. It will then be corrected for estimated patient blood volume and the amount of Hb transfused	Through study completion, an average of 14 months

Collaborators and Investigators

• Sponsor: Hemanext
• Collaborators: Johns Hopkins University; Emory University; University of Connecticut; Johns Hopkins All Children's Hospital; University of Pittsburgh Medical Center
• Investigators: Principal Investigator: Enrico Novelli, MD, MS, University of Pittsburgh Medical Center; Principal Investigator: Biree Andemariam, MD, New England Sickle Cell Institute, University of Connecticut; Principal Investigator: Laurel Omert, MD, FACS, Hemanext Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: December 12, 2024
• First Submitted That Met QC Criteria: December 16, 2024
• First Posted (Actual): December 19, 2024

Study Record Updates

• Last Update Posted (Actual): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Vaso-Occlusive Crises
• Other Study ID Numbers: PRO-CLIN-0017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No