Study to Evaluate Efficacy and Safety of S303 Treated Red Blood Cells (RBCs)in Subjects With Thalassemia Major Requiring Chronic RBC Transfusion

A Randomized Controlled Study to Evaluate Efficacy and Safety of S 303 Treated Red Blood Cells (RBC) in Subjects With Thalassemia Major Requiring Chronic RBC Transfusion

To evaluate the efficacy and safety of S 303 treated red blood cells (RBCs) in subjects who require chronic transfusion support due to thalassemia major.

Study Overview

• Status: Completed
• Conditions: Thalassemia Major
• Intervention / Treatment: Biological: S-303 Treated Red Blood Cells (RBCs); Biological: Conventional, untreated Red Blood Cells

Detailed Description

To evaluate the efficacy and safety of S 303 treated red blood cells (RBCs) in subjects who require chronic transfusion support due to thalassemia major.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Cagliari, Italy
    • Ospedale Regionale per le Microcitemie Azienda
  • Torino, Italy
    • University of Torino
• Turkey
  • Izmir, Turkey
    • Ege University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥10 years, of either gender
• Diagnosed with thalassemia major and currently participating in a chronic transfusion program
• At least a one year history of chronic RBC transfusion support with a stable transfusion requirement (per treating physician)
• Intervals of at least 14 days between RBC transfusions
• All RBC components are given on one day for each transfusion episode
• Negative direct antiglobulin tests (DAT)
• Stable iron chelation regimen
• Available for measurement of hemoglobin level at one hour post transfusion
• Signed and dated informed consent form

Exclusion Criteria:

• Baseline antibody specific to S 303 treated RBC (positive test, as defined in Section 8.4.1)
• Evidence of splenic hyper function defined as a transfusion requirement >180 cc/kg/year (at 100% hematocrit)
• Splenic enlargement: spleen palpable ≥4 cm below costal margin OR ≥18 cm in longitudinal diameter by ultrasound (chosen at the Investigator's discretion according to the data available with ultrasound data being preferable)
• Any subject for whom a transition in the number of RBC units transfused is anticipated within 12 months of study entry due to growth of the subject (e.g. a transition from 1 RBC component per transfusion cycle to 2 OR a transition from 2 to 3 is anticipated based on weight change alone)
• Alloimmunization to high frequency blood group antigens to the extent that the ready provision of compatible blood may not be feasible for the study (alloimmunization alone is not an automatic exclusion)
• Current specialized treatment with washed or frozen RBC
• Requirement for gamma irradiated RBC components (would present blinding difficulty due to blood component labeling regulations
• Treatment with any medication that is known to adversely affect RBC viability
• HIV infection (defined as RNA positive)
• HCV (hepatitis C)infection (defined as RNA positive) if treated with concomitant medications known to suppress the bone marrow
• Pregnant or breast feeding female, or female of child bearing potential not using a medically approved form of contraception
• Acute or chronic medical disorder other than thalassemia that, in the opinion of the Investigator or medical monitor, may prevent the subject from completing participation in the study
• Participation in another clinical study, either concurrently or within the previous 28 days, in which the study drug or device may influence red blood cell viability

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S-303 Treated Red Blood Cells (RBC); Patients will be randomly assigned to the sequence of administration of Test and Control RBCs; eligible patients are randomly assigned to receive Test RBCs followed by Control RBCs or Control RBCs followed by Test RBCs. Each patient will complete both treatment periods.	Biological: S-303 Treated Red Blood Cells (RBCs)
Active Comparator: Conventional, untreated Red Blood Cells; Patients will be randomly assigned to the sequence of administration of Test and Control RBCs; eligible patients are randomly assigned to receive Test RBCs followed by Control RBCs or Control RBCs followed by Test RBCs. Each patient will complete both treatment periods.	Biological: Conventional, untreated Red Blood Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Efficacy Endpoint - Hemoglobin consumption	Hemoglobin consumption measured as total hemoglobin mass transfused per subject adjusted for average body weight and the number of days during the efficacy evaluation period (adjusted hemoglobin (Hgb) consumption units are g Hgb/kg body weight/day).	12 months
Primary Safety Endpoint-Incidence of a treatment-emergent antibody with confirmed specificity to S 303 treated red blood cells (RBC)	Incidence of a treatment-emergent antibody with confirmed specificity to S 303 treated red blood cells (RBC) associated with clinically significant hemolysis	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Efficacy Endpoint-Hemoglobin increment	Hemoglobin increment one hour post-transfusion	12 months
Secondary Efficacy Endpoint-Proportional decline in post transfusion hemoglobin level per day (%/day)	Proportional decline in post transfusion hemoglobin level per day (%/day)	12 months
Secondary Safety Endpoint-Adverse Events	Subjects will be actively monitored for adverse events during the transfusion episode and until discharge from the transfusion clinic.	12 months
Secondary Safety Endpoint-Transfusion reactions within 24 hours	Transfusion reactions within 24 hours of a study transfusion with the assigned study product.	12 Months
Secondary Safety Endpoint-Frequency of allo immunization to red blood cell (RBC) allo-antigens	Frequency of allo immunization to red blood cell (RBC) allo-antigens	12 months

Collaborators and Investigators

• Sponsor: Cerus Corporation
• Investigators: Principal Investigator: Raffaella Origa, MD, Ospedale Regionale per le Microcitemie Azienda; Principal Investigator: Antonio Piga, MD, University of Torino; Principal Investigator: Yesim Aydinok, MD, Ege University, Izmir, Turkey

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2012
• Primary Completion (Actual): December 21, 2017
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: November 21, 2012
• First Submitted That Met QC Criteria: November 30, 2012
• First Posted (Estimate): December 4, 2012

Study Record Updates

• Last Update Posted (Actual): July 18, 2018
• Last Update Submitted That Met QC Criteria: July 16, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: S303 treated RBCs
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: CLI 00076