INTERCEPT Blood System for RBCs Study in Regions at Potential Risk for Zika Virus Transfusion-Transmitted Infections (RedeS)

• ClinicalTrials.gov Identifier: NCT03037164
• Recruitment Status: Recruiting
• First Posted: January 31, 2017
• Last Update Posted: April 2, 2021
• Sponsor: Cerus Corporation
• Information provided by (Responsible Party): Cerus Corporation

Study Description

Brief Summary:

Stage A: To evaluate the safety and efficacy of red blood cells (RBCs) prepared with the INTERCEPT Blood System for Red Blood Cells Pathogen Reduction Treatment (PRT) in comparison to conventional RBCs in patients who require RBC transfusion support.

Stage B: To provide early access to the INTERCEPT pathogen reduction system for RBC in regions where a substantial proportion of the population has been infected or is at risk of a transfusion-transmissible infection, and the risk of asymptomatic infection among qualified blood donors is recognized. Besides the reduction of risk of transfusion transmitted ZIKV, the intent of the study is also to reduce the risk of transfusion-transmitted infections (TTI) in general, including transfusion related sepsis and other emerging or concurrent endemic pathogens (e.g., SARS-CoV-2, Dengue and Chikungunya), and to potentially reduce the risk of TA-GVHD.

As part of this treatment use study, additional data will be provided on the safety of INTERCEPT-treated RBCs (IBS RBCs) supplied for routine clinical transfusion practice.

Condition or disease	Intervention/treatment	Phase
Anemia	Device: INTERCEPT Blood System for Red Blood Cells; Device: Conventional (Control)	Phase 3

Detailed Description:

Stage A

Eligible patients will be randomized and transfused with study RBCs (Test or Control with 1:1 ratio) according to local practices for up to 28 days of transfusion support. Following the 28-day acute transfusion support period, patients will be transfused with conventional RBC components as indicated by their treating physician unless they are enrolled in the optional follow-up extension study.

Non-bleeding patients at baseline requiring repeated RBC transfusion for congenital or acquired chronic anemia (e.g., sickle anemia, thalassemia, other hemoglobinopathies, myelodysplastic syndrome, aplastic anemia, chemotherapy or stem cell transplant etc.) will be eligible to participate in an extension option for up to 6 months to evaluate patients requiring repeated transfusion for chronic anemia. Subjects will receive the same study article (Test or Control RBC) as assigned in the initial 28-day study period. Following participation in the optional 6-month extended transfusion support period, patients will be transfused with conventional RBC components as indicated by their treating physician.

Screening/Recruitment

All potentially eligible patients at participating institutions will be approached for study consent. Subjects <18 years of age will require subject assent and parental consent. For subjects eligible for enrollment into the 6-month extension period option, consent/assent for the extension period should be obtained at initial enrollment.

Patients who consent to the study will be assigned a study ID number and undergo screening. Screening data collection and procedures will include:

Demographics (age, sex), vital signs, height, weight, indication for anticipated transfusion, type of scheduled surgery (if applicable), medical and surgical history, transfusion history, physical examination, comorbid conditions, concomitant medications, hematology panel (including complete blood count), blood type and Rh, Indirect Antiglobulin Test (IAT), blood chemistry, coagulation panel, Direct Antiglobulin Test (DAT), immune reactivity to IBS RBCs, pregnancy test (when applicable). Once all screening assessments are completed and eligibility is confirmed, the subject may be randomized.

If results from the following assessments are available in the medical record within 30 days prior to randomization, those data may serve as the screening data and the assessments do not need to be repeated unless the subject has an RBC transfusion in the 30-day period:

• hematology panel (complete blood count), blood chemistry and coagulation panel
• blood type and Rh
• IAT, DAT, and immune reactivity to IBS RBCs
• physical examination

If a RBC transfusion occurs after the study specific blood draws and assessments to determine eligibility are taken but prior to randomization, the subject may be randomized and the tests listed above should repeated prior to the first study transfusion.

A pregnancy test (when applicable) must be performed within 7 days of randomization.

Randomization and Blinding

For Stage A, potentially eligible patients will be consented and begin screening in the study in order to be considered for randomization. An Interactive Web Response System (IWRS) will be used for electronic randomization of eligible patients.

Randomization will be at a 1:1 ratio of Test: Control and stratified by site, baseline bleeding status [indication for RBC transfusion due to active bleeding (WHO Grade 3 or 4, APPENDIX 5) or for anemia without active bleeding], and non-bleeding patients' participation of the optional extension period (yes/no). Anticipated surgical bleeding and planned blood loss/replacement through red cell exchange at baseline should be included as active bleeding (Grade ≥3) by definition. Randomized patients who do not receive any study RBC transfusions through 28 days after randomization will be withdrawn from the study and replaced. Additional data will not be collected for these patients. These subjects may be reassessed for eligibility and re-enrollment after withdrawal.

At the end of screening, the patient's eligibility status will be entered into the electronic data capture system (EDC). If eligible, the patient will be randomized. Only appropriate blood bank staff will be able to access the treatment arm assignment. Study RBC unit labels will be indistinguishable for Test and Control products. Medical staff, and others caring for participating patients, as well as the sponsor (and delegates) will be blinded to treatment assignment. Unblinded delegates will monitor the production of the RBC components at designated blood centers.

Stage B has an open-label, single-arm design, hence no randomization or blinding procedures are required

Treatment

Randomized patients will be transfused with Test or Control RBC components for up to 28 days in the initial acute transfusion period and for an additional 6-months if the subject is entered into the optional extension period. Subjects participating in Stage A's optional extended study will continue to receive the same study article (Test or Control RBC) as in their initial 28-day study period. An RBC transfusion episode is defined to include consecutive RBC units transfused with ≤12 hours between transfusions (from the end of a prior component transfused to the start of a subsequent component transfused). A confirmed negative immune reaction to IBS RBC is required prior to the first study transfusion and at every time point a Type/Rh and Screen (IAT) is performed for a patient within the 28-day acute transfusion period or during the extension period. Compatibility for RBC antigens will be confirmed using site's SOPs prior to transfusion of study RBCs. In case of confirmed physiologically active antibodies to IBS RBC or any presumed or documented antibodies to IBS RBC that preclude further transfusion with study RBCs, patients will be withdrawn from the study treatment and supported with conventional RBC components and followed for safety. Patients with antibodies to IBS RBC will be investigated for evidence of hemolysis and continue with all planned visits and safety monitoring.

Study Assessments: Monitoring and Follow-up

Acute Transfusion Support Period (First study transfusion through Day 28 or death) and the optional extension period (if applicable).

The acute transfusion support period will comprise 28 days from the day of the first study transfusion (Day 1) through Day 28, or death of a patient, plus an additional optional 6-month transfusion period for those patients entered into the extension period. During these periods, patients will receive as many study RBCs as deemed appropriate by the treating physician. All AEs, SAEs, TRs and unanticipated adverse device effects will be collected starting from the initiation of the first study transfusion through 28 days after the last study transfusion. The Investigators will assess each AE/SAE/TR and unanticipated adverse device effects for relation to the transfused study RBCs. Transfusion reactions will be classified by the definitions in the CDC NHSN Hemovigilance Module Surveillance Protocol (APPENDIX 1) and will be captured in the eCRF and, if in routine use, in the CDC NHSN Biovigilance Component/Hemovigilance Module (www.cdc.gov/nhsn).

Most proximate vital signs in the medical record will be collected prior to and following each study transfusion. The subject's hemoglobin value will be collected from the medical record, or if not available, a study sample will be submitted for testing, prior to and following each study transfusion episode within 15 minutes to 24 hours after the end of the transfusion episode and before the next RBC transfusion.

Relevant concomitant medications taken during the study and blood products transfused will be recorded with indication, total daily dose, and dates of drug administration.

During the acute transfusion support period, patients will undergo the following assessments prior to each transfusion episode: vital signs, AEs, TRs, SAEs and unanticipated adverse device effects, comorbid conditions, blood samples for safety labs (complete blood count, blood chemistry panel), IAT and immune reactivity to IBS RBCs. Samples may be used for additional in vitro research tests as required to confirm transfusion-transmitted pathogen mediated infections.

An immune reactivity to IBS RBCs test will be performed and resulted each time an IAT is performed within the 28-day acute and 6-month extension transfusion support period.

Follow-Up Period (28 and 75 days after last study transfusion)

For the purposes of the Day 28 (± 7 days) and Day 75 (± 15 days) follow-up visits, Day 1 of the follow-up period is the day after the last study transfusion, either in the initial 28 day acute transfusion period or, if the subject is entered, in the optional extension period.

Day 28 (± 7 days) After the Last Study Transfusion

Vital signs will be collected, and blood samples will be collected for:

1. Routine safety labs (complete blood count, blood chemistry panel, hematology panel, and coagulation panel)
2. DAT and IAT
3. Immune reactivity test for IBS RBC

All AEs, SAEs, TRs and unanticipated adverse device effects will be reviewed and recorded for the period from the first study transfusion through 28 days after the last study transfusion.

End of Study Visit (Day 75 ±15 days)

Day 75 (± 15 days) after the last study transfusion either in the initial 28 day acute transfusion period or after the extension period, a blood sample will be collected for a DAT and immune reactivity test for IBS RBC.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-Blind, Controlled, Parallel Group Study With the INTERCEPT Blood System for RBCs in Regions at Potential Risk for Zika Virus Transfusion-Transmitted Infections and Treatment Use Open-Label Extension Study
• Actual Study Start Date: May 11, 2017
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: January 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: INTERCEPT (Test); Red blood cell components treated with the INTERCEPT Blood System for Red Blood Cells ordered and administered to study patients by their treating physicians according to the local standards of care	Device: INTERCEPT Blood System for Red Blood Cells; The pathogen reduction process begins with a unit of RBCs derived from whole blood that is separated according to local regulations and standard operating procedures at the Blood Centers. RBCs are suspended in AS-5. Leukocyte-reduction of whole blood or RBCs will be performed per manufacturer's instructions. The INTERCEPT Blood System process is performed on a single unit of leukocyte-depleted RBC in AS-5.
Active Comparator: Conventional (Control); Conventional RBC components ordered and administered to study patients by their treating physicians according to the local standards of care	Device: Conventional (Control); Conventional RBC components ordered and administered to study patients by their treating physicians according to the local standards of care

Outcome Measures

Primary Outcome Measures :

1. Adjusted hemoglobin increment [ Time Frame: 15 minutes - 24 hours post transfusion ]
   The difference between the pre-transfusion and post transfusion episode hemoglobin values divided by the total hemoglobin content transfused, averaged over multiple transfusion episodes in patients without active bleeding at baseline (active bleeding is defined as WHO Grade 3 or 4 bleeding)
2. Adverse Events [ Time Frame: 28 days ]
   Proportion of patients with any treatment-emergent adverse events (AEs) possibly, probably, or definitely related to study RBC transfusion through 28 days after the last study transfusion.
3. Treatment emergent antibodies [ Time Frame: 75 days ]
   The proportion of patients with treatment emergent antibodies with confirmed specificity to IBS RBCs

Secondary Outcome Measures :

1. Adjusted hemoglobin consumption [ Time Frame: 28 Days ]
   defined as total hemoglobin mass transfused in grams divided by body weight in kg at baseline and duration of the study transfusion period in days (g/kg/day), in patients without active bleeding at baseline.
2. Adverse Events [ Time Frame: 28 Days after last study transfusion ]
   Treatment-emergent AEs
3. Transfusion reactions related to study RBCs (test or control) [ Time Frame: 28 Days after last study transfusion ]
   Defined by the CDC National Healthcare Safety Network [NHSN] Hemovigilance Module protocol
4. RBC allo-antigens [ Time Frame: 28 days ]
   Treatment-emergent immunization to RBC allo-antigens
5. Mortality [ Time Frame: 28 Days after last study transfusion ]
   All-cause mortality

Eligibility Criteria

• Ages Eligible for Study: 4 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Stage A: Inclusion Criteria:

• Age ≥ 4 years
• Patients who require or are expected to require a transfusion of RBC component(s), including red cell exchange transfusion.
• Signed and dated informed consent

• Female patients of child-bearing potential must:

  • Have negative serum or urine pregnancy tests prior to study treatment to rule out pregnancy, and
  • Use at least one method of birth control that results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner for the duration of study participation and an additional 28 days

Stage A: Exclusion Criteria

• Confirmed positive baseline serum/plasma antibody specific to IBS RBC (S-303 treated RBC) as determined by INTERCEPT antibody screening panel prior to receiving the first study transfusion
• Pregnant or breast feeding.
• Presence of a RBC warm autoantibody

• Positive DAT as defined below:

  • A polyspecific-DAT reaction strength > 2+, or
  • A polyspecific-DAT (any strength) in conjunction with pan-reactivity with a commercial IAT antibody screening panel that precludes the identification of underlying alloantibodies or indicates the presence of autoantibody
• Have had an RBC transfusion within 14 days prior to S-303 antibody screen for eligibility
• Have received investigational products, including investigational blood products, pharmacologic agents or imaging materials, within the prior 28 days to randomization. Prior receipt of conventional blood products tested with an investigational NAT test are not considered grounds for exclusion.
• Patients presenting with or expected to have massive hemorrhage (≥10 RBC units within 24 hours) or expected to require massive transfusion protocols. Planned red cell exchange does not apply.
• Patients who require neonatal transfusions and intrauterine transfusions.
• Pre-existing antibody to RBC antigens that may make the provision of compatible study RBC components difficult.
• History of transfusion reactions requiring washed RBCs, volume reduced RBC, or RBCs with additive solution removed.
• Patients with documented IgA deficiency or a history of severe allergic reactions to blood products
• Subjects on regular long-term red cell exchange protocols will not be enrolled into the 6-month extension option

Stage B: Inclusion Criteria

• Age ≥ 4 years
• Patients expected to require or requiring a transfusion of RBC component(s), including red cell exchange transfusion.
• Signed and dated informed consent and assent (if applicable)

• Female patients of child-bearing potential must:

  • Have negative serum or urine pregnancy tests prior to study treatment to rule out pregnancy, and
  • Use at least one method of birth control that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner for the duration of study participation and an additional 28 days

Stage B: Exclusion Criteria

• Confirmed positive baseline serum/plasma antibody specific to IBS RBC as determined by antibody screening panel to S-303 treated RBC prior to receiving their first study transfusion.
• Pregnant or breast feeding.
• Patients who require neonatal transfusions and intrauterine transfusions.
• Patients with documented IgA deficiency or a history of severe allergic reactions to blood products.
• Pre-existing antibody to RBC antigens that may make the provision of compatible study RBC components difficult.
• History of transfusion reactions requiring washed RBCs, volume reduced RBC, or RBCs with additive solution removed

Contacts and Locations

Contacts

Contact: Chris Marston; 1-949-275-8702; cmarston@cerus.com

Contact: Nell Shimasaki; 1-925-288-6116; nshimasaki@cerus.com

Locations

United States, Connecticut

Yale University; Recruiting

New Haven, Connecticut, United States, 06520

Contact: Edward Snyder, MD 203-688-2443

Principal Investigator: Edward Snyder, MD

United States, Florida

Mayo Clinic Jacksonville; Active, not recruiting

Jacksonville, Florida, United States, 32224

United States, Georgia

Grady Health System; Recruiting

Atlanta, Georgia, United States, 30303

Contact: Ross Fasano, MD scdresearch@emory.edu

Contact: Hailly Butler, BSN

United States, Texas

UT Southwestern Medical Center; Recruiting

Dallas, Texas, United States, 75390

Contact: Ravi Sarode, MD Ravi.Sarode@UTSouthwestern.edu

Baylor St. Luke's Medical Center; Recruiting

Houston, Texas, United States, 77303

Contact: Elizabeth Hartwell, MD hartwell@bcm.edu

United States, Virginia

Virginia Commonwealth University; Recruiting

Richmond, Virginia, United States, 23298

Contact: Jeffrey A Green, Dr jeffrey.green@vcuhealth.org

Puerto Rico

Menonita General Hospital; Recruiting

Aibonito, Puerto Rico, 00705

Contact: Lumen Vera, Dr. lvera@mghpr.org

HIMA San Pablo Hospital; Recruiting

Caguas, Puerto Rico, 00725

Contact: Bolivar Arboleda, Dr. 787-653-3434

San Juan Bautista School of Medicine Clinical Research Unit; Recruiting

Caguas, Puerto Rico, 00725

Contact: Edgardo Cartagena, Dr. ecartagena@sanjuanbautista.edu

Sponsors and Collaborators

Cerus Corporation

More Information

• Responsible Party: Cerus Corporation
• ClinicalTrials.gov Identifier: NCT03037164
• Other Study ID Numbers: CLI 00126
• First Posted: January 31, 2017
• Last Update Posted: April 2, 2021
• Last Verified: March 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Cerus Corporation:

INTERCEPT; Red Blood Cells; RBC; Pathogen Inactivation; Zika; Cerus; Pathogen Reduction

Additional relevant MeSH terms:

Transfusion Reaction; Hematologic Diseases; Immune System Diseases