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A Pilot Study to Assess the Safety and Efficacy of Alefacept in de Novo Kidney Transplant Recipients

Primary Purpose

Transplant; Failure, Kidney

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Alefacept (ASP0485)

About this trial

This is an interventional treatment trial for Transplant; Failure, Kidney focused on measuring Kidney, Transplant, Northwestern, Calcineurin Inhibitor, Corticosteroids, Steroid avoidance

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Institutional Review Board (IRB) approved written Informed Consent and Health Insurance Portability and Accountability Act (HIPAA) Authorization for U.S. sites, or equivalent privacy language as per national regulations, obtained from the subject or legally authorized representative prior to study-related procedures (including withdrawal of prohibited medication, if applicable)
Recipient of a kidney from a non-HLA identical related living donor, a non- related living donor, or deceased donor
Recipient of a de novo kidney transplant
≥ 18 years of age
Anticipated to receive first oral dose of tacrolimus within 48 hours of transplant procedure
Female subjects of child bearing potential must have a negative urine or serum pregnancy test, and must agree to maintain effective birth control during the study

Healthy donor is eligible for the blood draw if:

Institutional Review Board (IRB) approved written Informed Consent and Health Insurance Portability and Accountability Act (HIPAA) Authorization for U.S. sites, or equivalent privacy language as per national regulations, is obtained from subject prior to any study-related procedures
Subject is a donor to a de novo kidney transplant subject who is enrolled in the study or a self declared healthy volunteer who is not a kidney donor for a subject enrolled in the study
≥ 18 years of age

Exclusion Criteria:

Previously received or is receiving an organ transplant other than a kidney
Sensitivity to iodine
Will receive a transplant from a non-heart beating donor (donation after cardiac death - DCD)
Receives a transplant from an HLA identical related living donor
Will receive a solitary kidney from a deceased donor < 5 years of age
Will receive a kidney with an anticipated cold ischemia time (CIT) of > 30 hours
Will receive an ABO incompatible donor kidney
Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV)
Recipient has a positive T or B cell crossmatch by investigational site's standard method of determination. For recipients where a flow cytometry crossmatch is performed and is positive in either T or B cell testing, recipients are excluded only if donor specific, anti-HLA antibody is detected by flow cytometry based, specific anti-HLA antibody testing.
Current malignancy or a history of malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully
Significant liver disease
Serologically negative for cytomegalovirus (CMV) with serologically positive CMV donor
Serologically negative for Epstein Barr virus
Has received intravenous immunoglobulin (IVIG) therapy in the three months prior to first dose of study drug
Uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives
Concurrently participating in another drug study or has received an investigational drug within 28 days prior to transplant
Known hypersensitivity to alefacept, alemtuzumab, tacrolimus, mycophenolic acid, corticosteroids, or any of their components
Any form of substance abuse, psychiatric disorder, or a condition that in the opinion of the Investigator could invalidate communication with the Investigator
Subject is pregnant or lactating
Subject is unlikely to comply with the visits scheduled in the protocol
Subject will receive a kidney transplant from an expanded criteria donor (ECD)
Will receive a kidney transplant from a CDC high risk donor

Healthy donor subject will be excluded from participation if any of the following apply:

Unable to comprehend the investigational nature of the protocol participation
Complete blood count results determined to be outside the normal ranges

Sites / Locations

Northwestern Memorial Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Alefacept (ASP0485)

Arm Description

Safety and efficacy of alefacept in combination with alemtuzumab induction and calcineurin inhibitor (CNI) and corticosteroid withdrawal.

Outcomes

Primary Outcome Measures

Incidence of first biopsy- proven acute rejection (Banff Grade≥ 1) (BCAR rate) and infections

To assess the safety and efficacy of alefacept in combination with a single dose of alemtuzamab induction and Enteric coated Mycophenolic sodium with calcineurin inhibitor withdrawal and rapid elimination of corticosteroids by examining the incidence of first biopsy-proven acute rejection (Banff Grade≥ 1) (BCAR rate) and the incidence and clinical presentation of infections.

Secondary Outcome Measures

Affect on Immune cells

To assess how alefacept affects T-cell differentiation, memory, and immunoregulatory T-cell homeostasis, B-cells and cytokine/chemokine profile by using various immune monitoring assays.

Assess secondary outcome measures of efficacy and safety

At 12 months: Patient/graft survival rates, BCAR rate, Maximum grade of acute rejection with BCAR, Incidence of clinically-treated acute rejections, Incidence of anti-lymphocyte antibody therapy for treatment of rejection, Incidence of multiple rejection episodes, Incidence of treatment failure (defined as death, graft loss, biopsy-confirmed acute rejection, lost to follow-up or early discontinuation of treatment regimen), Incidence of leucopenia, Incidence of bacterial, fungal, viral, or parasitic infection. At 6 & 12 months: Serum creatinine, GFR by iohexol clearance. Time to first BCAR

Full Information

NCT ID

NCT01163799

First Posted

July 14, 2010

Last Updated

May 1, 2013

Sponsor

Northwestern University

Collaborators

Astellas Pharma Inc

1. Study Identification

Unique Protocol Identification Number

NCT01163799

Brief Title

A Pilot Study to Assess the Safety and Efficacy of Alefacept in de Novo Kidney Transplant Recipients

Official Title

A Pilot Study to Assess the Safety and Efficacy of Alefacept in de Novo Kidney Transplant Recipients

Study Type

Interventional

2. Study Status

Record Verification Date

May 2013

Overall Recruitment Status

Terminated

Why Stopped

Noted increased risks, greater than expected for standard of care therapy.

Study Start Date

July 2010 (undefined)

Primary Completion Date

September 2011 (Actual)

Study Completion Date

August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Northwestern University

Collaborators

Astellas Pharma Inc

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to assess Alefacept in combination with alemtuzumab induction and calcineurin inhibitor and corticosteroid withdrawal.

Detailed Description

This is a single center, investigator initiated, pilot study to assess the safety and efficacy of Alefacept in combination with Alemtuzumab induction and Myfortic with rapid steroid and calcineurin inhibitor withdrawal in de novo Kidney transplant recipients. Induction therapy involves single dose Alemtuzumab and steroids peri-operatively. Tacrolimus will be administered for the first 30 days post-transplantation. Alefacept will be administered IV for the first two doses followed by subcutaneous injections weekly until 12 weeks post-transplant followed by monthly injections for the rest of the duration of the study. The primary outcomes are safety and efficacy outcomes, including biopsy proven acute rejection episodes, infectious complications or other serious adverse events. Secondary outcomes include T-helper differentiation, cytokine production and T regulatory cell generation assessed by immune monitoring assays.

6. Conditions and Keywords

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

Transplant; Failure, Kidney

Keywords

Kidney, Transplant, Northwestern, Calcineurin Inhibitor, Corticosteroids, Steroid avoidance

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Alefacept (ASP0485)

Arm Type

Experimental

Arm Description

Safety and efficacy of alefacept in combination with alemtuzumab induction and calcineurin inhibitor (CNI) and corticosteroid withdrawal.

Intervention Type

Drug

Intervention Name(s)

Alefacept (ASP0485)

Other Intervention Name(s)

ASP0485

Intervention Description

Withdrawal of calcineurin inhibitor at 30 days post-transplant. Administer Alefacept 7.5 mg post-op day 0, post-op day 2 given IV; Alefacept 15 mg SQ X 12 weeks, then monthly until Month 12.

Primary Outcome Measure Information:

Title

Incidence of first biopsy- proven acute rejection (Banff Grade≥ 1) (BCAR rate) and infections

Description

Time Frame

At 12 months post-transplant

Secondary Outcome Measure Information:

Title

Affect on Immune cells

Description

To assess how alefacept affects T-cell differentiation, memory, and immunoregulatory T-cell homeostasis, B-cells and cytokine/chemokine profile by using various immune monitoring assays.

Time Frame

Up to 12 months post-transplant

Title

Assess secondary outcome measures of efficacy and safety

Description

Time Frame

Upto 12 months post-transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Institutional Review Board (IRB) approved written Informed Consent and Health Insurance Portability and Accountability Act (HIPAA) Authorization for U.S. sites, or equivalent privacy language as per national regulations, obtained from the subject or legally authorized representative prior to study-related procedures (including withdrawal of prohibited medication, if applicable) Recipient of a kidney from a non-HLA identical related living donor, a non- related living donor, or deceased donor Recipient of a de novo kidney transplant ≥ 18 years of age Anticipated to receive first oral dose of tacrolimus within 48 hours of transplant procedure Female subjects of child bearing potential must have a negative urine or serum pregnancy test, and must agree to maintain effective birth control during the study Healthy donor is eligible for the blood draw if: Institutional Review Board (IRB) approved written Informed Consent and Health Insurance Portability and Accountability Act (HIPAA) Authorization for U.S. sites, or equivalent privacy language as per national regulations, is obtained from subject prior to any study-related procedures Subject is a donor to a de novo kidney transplant subject who is enrolled in the study or a self declared healthy volunteer who is not a kidney donor for a subject enrolled in the study ≥ 18 years of age Exclusion Criteria: Previously received or is receiving an organ transplant other than a kidney Sensitivity to iodine Will receive a transplant from a non-heart beating donor (donation after cardiac death - DCD) Receives a transplant from an HLA identical related living donor Will receive a solitary kidney from a deceased donor < 5 years of age Will receive a kidney with an anticipated cold ischemia time (CIT) of > 30 hours Will receive an ABO incompatible donor kidney Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV) Recipient has a positive T or B cell crossmatch by investigational site's standard method of determination. For recipients where a flow cytometry crossmatch is performed and is positive in either T or B cell testing, recipients are excluded only if donor specific, anti-HLA antibody is detected by flow cytometry based, specific anti-HLA antibody testing. Current malignancy or a history of malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully Significant liver disease Serologically negative for cytomegalovirus (CMV) with serologically positive CMV donor Serologically negative for Epstein Barr virus Has received intravenous immunoglobulin (IVIG) therapy in the three months prior to first dose of study drug Uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives Concurrently participating in another drug study or has received an investigational drug within 28 days prior to transplant Known hypersensitivity to alefacept, alemtuzumab, tacrolimus, mycophenolic acid, corticosteroids, or any of their components Any form of substance abuse, psychiatric disorder, or a condition that in the opinion of the Investigator could invalidate communication with the Investigator Subject is pregnant or lactating Subject is unlikely to comply with the visits scheduled in the protocol Subject will receive a kidney transplant from an expanded criteria donor (ECD) Will receive a kidney transplant from a CDC high risk donor Healthy donor subject will be excluded from participation if any of the following apply: Unable to comprehend the investigational nature of the protocol participation Complete blood count results determined to be outside the normal ranges

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

M. Javeed Ansari, MD

Organizational Affiliation

Northwestern Universiy, Northwestern Memorial Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Northwestern Memorial Hospital

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

12. IPD Sharing Statement

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A Pilot Study to Assess the Safety and Efficacy of Alefacept in de Novo Kidney Transplant Recipients

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