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A Prospective, Open Label, Phase 1 Safety Study of Passive Immune Therapy During Acute Ebola Virus Disease Using Transfusion of INTERCEPT Plasma Prepared From Volunteer Donors Who Have Recovered From Ebola Virus Disease

Primary Purpose

Acute Ebola Virus Disease

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

INTERCEPT Plasma

About this trial

This is an interventional treatment trial for Acute Ebola Virus Disease focused on measuring Pathogen inactivation, ebola, convalescent plasma, EBOV, amotosalen, Provide access to the potential therapeutic benefit of EBOV convalescent plasma containing antibodies to EBOV.

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

EBOV Convalescent Donor Inclusion Criteria:

Recovered from Ebola Virus Disease (EVD) by clinical criteria and declared clinically asymptomatic of active EVD.
Twenty-eight (28) days from hospital discharge.
Two negative test results for EBOV nucleic acid by a sensitive nucleic acid test method with blood samples drawn at least 48 hours apart.
Plasma/serum tested for HIV, HTLV, HCV, HBV, syphilis, and other pathogens (per institutional practice) using licensed test methods. Inclusion of donors with positive test results for these pathogens will be at the discretion of treating physicians, with respect to the relative benefit of donor subject convalescent plasma treated with INTERCEPT pathogen inactivation, compared to the risk to recipients of not receiving EBOV convalescent plasma transfusion therapy.
ABO blood group and RhD typing performed and donor anti-A and anti-B titers performed.
Plasma/serum tested for human leukocyte antigen (HLA) antibodies for female donors with history of pregnancy and for donors with a history of transfusions (per institutional practice) using licensed test methods for transfusion-related acute lung injury (TRALI) risk mitigation. Inclusion of donors with positive test results will be at the discretion of treating physicians, with respect to the relative benefit of donor subject convalescent plasma compared to the risk to recipients of not receiving EBOV convalescent plasma transfusion therapy.
Measurement of antibodies to EBOV, when feasible and ultimately measurement of neutralizing antibodies to EBOV, when available.
Conformity to age and weight standards for blood donors for plasma donation. Variance from standards may be acceptable with evaluation by treating physician(s) and with donor or legal guardian consent for non-conforming donors when collection of reduced volumes of plasma may be of therapeutic value.
Cleared by treating physician for apheresis plasma donation.
Written signed informed consent to donate 650-1300 mL plasma by apheresis at frequencies of twice per week, at the discretion of the treating physician.

Recipient Subject Inclusion Criteria:

Acute EVD diagnosed by nucleic acid testing and meeting established case definitions (World Health Organization 2014).
Subject or legal guardian provides written informed consent to receive INTERCEPT plasma.

Exclusion Criteria:

EBOV Convalescent Donor Exclusion Criteria:

• Active EVD

Recipient Subject Exclusion Criteria:

• Documented food allergy to psoralens

Sites / Locations

Emory University
University of Nebraska Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

EBOV convalescent donors

Arm Description

EBOV convalescent donors for passive immune therapy in subjects with acute EVD

Outcomes

Primary Outcome Measures

Proportion of subjects who survive EVD

Proportion of subjects with adverse events

Proportion of subjects with Serious Adverse Events

Secondary Outcome Measures

Time from diagnosis of acute EVD to death due to acute EVD

Proportion of subjects with clinical remission, where clinical remission is defined as absence of clinical symptoms indicative of EVD and at least two negative EBOV nucleic acid tests at least 48 hours apart prior to hospital discharge.

Time from diagnosis of acute EVD to clinical remission.

Reduction of EBOV viral load titers by nucleic acid testing prior to hospital discharge.

Subject hemostatic function pre INTERCEPT plasma and post last INTERCEPT plasma transfusion (prior to discharge), as available: o Prothrombin time o International Normalized Ratio (INR) o Activated partial thromboplastin time o Fibrinogen activity

Full Information

NCT ID

NCT02295501

First Posted

November 4, 2014

Last Updated

March 26, 2021

Sponsor

Cerus Corporation

1. Study Identification

Unique Protocol Identification Number

NCT02295501

Brief Title

A Prospective, Open Label, Phase 1 Safety Study of Passive Immune Therapy During Acute Ebola Virus Disease Using Transfusion of INTERCEPT Plasma Prepared From Volunteer Donors Who Have Recovered From Ebola Virus Disease

Official Title

A Prospective, Open Label Observational, Phase 1 Safety Study of Passive Immune Therapy During Acute Ebola Virus Disease Using Transfusion of INTERCEPT Plasma Prepared From Volunteer Donors Who Have Recovered From Ebola Virus Disease

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Terminated

Why Stopped

The study was terminated on expiry of the frozen and stored plasma components.

Study Start Date

December 2014 (undefined)

Primary Completion Date

December 2020 (Actual)

Study Completion Date

December 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cerus Corporation

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Detailed Description

The objective of this Phase 1 safety study is to provide access to the potential therapeutic benefit of EBOV convalescent plasma containing antibodies to EBOV. The risk of exposure to plasma from donors who may be infected with other transfusion-transmitted pathogens, not detectable by current licensed donor testing procedures, will be mitigated by using pathogen inactivation to minimize the risk of the TTI from these donors, who would otherwise be deferred and ineligible for blood donation. The study is designed as a prospective, open label, multi-center, single arm study to evaluate the safety and efficacy of INTERCEPT plasma prepared from EBOV convalescent donors for passive immune therapy in subjects with acute EVD. Data will be collected to assess the safety of this intervention by monitoring adverse events in the immediate 24-hour post transfusion period. Efficacy will be assessed by monitoring the clinical status of treated subjects with respect to clearance of EBOV by using nucleic acid assays to measure pre and post treatment viral titers. A number of clinical parameters indicative of end-organ damage during acute EVD will be monitored to determine if passive immune therapy affects the onset and duration of renal failure and acute lung injury. In addition, blood samples will be collected pre and post transfusion of convalescent EBOV INTERCEPT plasma to determine if biomarkers of endothelial injury are impacted, and if they can be used to guide plasma transfusion therapy to establish a dosing regimen and duration of treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Ebola Virus Disease

Keywords

Pathogen inactivation, ebola, convalescent plasma, EBOV, amotosalen, Provide access to the potential therapeutic benefit of EBOV convalescent plasma containing antibodies to EBOV.

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

EBOV convalescent donors

Arm Type

Experimental

Arm Description

EBOV convalescent donors for passive immune therapy in subjects with acute EVD

Intervention Type

Biological

Intervention Name(s)

INTERCEPT Plasma

Other Intervention Name(s)

INTERCEPT Blood System for Plasma

Intervention Description

Plasma will be collected from eligible volunteer donors who have recovered from acute EVD (see EBOV convalescent donor inclusion criteria). This donor plasma will be collected by apheresis donation (approximately 650-1300 mL per donation at physician discretion) and treated with the IBS for plasma.

Primary Outcome Measure Information:

Title

Proportion of subjects who survive EVD

Time Frame

through hospital discharge up to 1 year

Title

Proportion of subjects with adverse events

Time Frame

Up to 24 hours post transfusion

Title

Proportion of subjects with Serious Adverse Events

Time Frame

Up to 7 days post-transfusion

Secondary Outcome Measure Information:

Title

Time from diagnosis of acute EVD to death due to acute EVD

Time Frame

censored at hospital discharge up to 1 year

Title

Time Frame

through hospital discharge up to 1 year

Title

Time from diagnosis of acute EVD to clinical remission.

Time Frame

through hospital discharge up to 1 year

Title

Reduction of EBOV viral load titers by nucleic acid testing prior to hospital discharge.

Time Frame

through hospital discharge up to 1 year

Title

Time Frame

pre and post transfusion up to 1 year

10. Eligibility

Sex

All

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: EBOV Convalescent Donor Inclusion Criteria: Recovered from Ebola Virus Disease (EVD) by clinical criteria and declared clinically asymptomatic of active EVD. Twenty-eight (28) days from hospital discharge. Two negative test results for EBOV nucleic acid by a sensitive nucleic acid test method with blood samples drawn at least 48 hours apart. Plasma/serum tested for HIV, HTLV, HCV, HBV, syphilis, and other pathogens (per institutional practice) using licensed test methods. Inclusion of donors with positive test results for these pathogens will be at the discretion of treating physicians, with respect to the relative benefit of donor subject convalescent plasma treated with INTERCEPT pathogen inactivation, compared to the risk to recipients of not receiving EBOV convalescent plasma transfusion therapy. ABO blood group and RhD typing performed and donor anti-A and anti-B titers performed. Plasma/serum tested for human leukocyte antigen (HLA) antibodies for female donors with history of pregnancy and for donors with a history of transfusions (per institutional practice) using licensed test methods for transfusion-related acute lung injury (TRALI) risk mitigation. Inclusion of donors with positive test results will be at the discretion of treating physicians, with respect to the relative benefit of donor subject convalescent plasma compared to the risk to recipients of not receiving EBOV convalescent plasma transfusion therapy. Measurement of antibodies to EBOV, when feasible and ultimately measurement of neutralizing antibodies to EBOV, when available. Conformity to age and weight standards for blood donors for plasma donation. Variance from standards may be acceptable with evaluation by treating physician(s) and with donor or legal guardian consent for non-conforming donors when collection of reduced volumes of plasma may be of therapeutic value. Cleared by treating physician for apheresis plasma donation. Written signed informed consent to donate 650-1300 mL plasma by apheresis at frequencies of twice per week, at the discretion of the treating physician. Recipient Subject Inclusion Criteria: Acute EVD diagnosed by nucleic acid testing and meeting established case definitions (World Health Organization 2014). Subject or legal guardian provides written informed consent to receive INTERCEPT plasma. Exclusion Criteria: EBOV Convalescent Donor Exclusion Criteria: • Active EVD Recipient Subject Exclusion Criteria: • Documented food allergy to psoralens

Facility Information:

Facility Name

Emory University

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

University of Nebraska Medical Center

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68198

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

32129478

Citation

Dean CL, Hooper JW, Dye JM, Zak SE, Koepsell SA, Corash L, Benjamin RJ, Kwilas S, Bonds S, Winkler AM, Kraft CS. Characterization of Ebola convalescent plasma donor immune response and psoralen treated plasma in the United States. Transfusion. 2020 May;60(5):1024-1031. doi: 10.1111/trf.15739. Epub 2020 Mar 4.

Results Reference

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