Safety and Efficacy Study of Thymoglobulin Versus IL2 Receptor Antagonists

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT00859131
• Collaborator: Genzyme, a Sanofi Company (Industry)
• Enrollment: 200
• Location: 1
• Arms: 2
• Duration (Months): 64
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of induction therapy with Thymoglobulin in comparison with IL2 receptor antagonists (daclizumab or basiliximab).

Condition or Disease	Intervention/Treatment	Phase
End Stage Renal Disease	Drug: Rabbit Antithymocyte globulin; Drug: Daclizumab	N/A

Detailed Description

A 12 month, prospective, randomized, single center, open-label study to evaluate the safety and efficacy of Rabbit anti-thymocyte globulin versus IL2 receptor antagonists in combination with tacrolimus, corticosteroids and mycophenolate mofetil in a predominantly high risk kidney transplant population.

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Official Title: Rabbit Anti-thymocyte Globulin Versus IL2 Receptor Antagonists in Combination With Tacrolimus, Corticosteroids and Mycophenolate Mofetil in a Predominantly High Risk Kidney Transplant Population.
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Thymoglobulin Subjects receiving Thymoglobulin as induction agent in renal transplantation	Drug: Rabbit Antithymocyte globulin; 1.5 mg/kg IV pre-op, day 1, day 2, day 3, day 4; Other Names: Thymoglobulin
Active Comparator: Zenapax subject who will receive daclizumab or basiliximab as induction agent in renal transplantation	Drug: Daclizumab; 1.0 mg/kg pre-op and 1.0 mg/kg on Day 7; Other Names: daclizumab, zenapax

Outcome Measures

Primary Outcome Measures

1. Treatment Efficacy Will be Defined as the Number of Patients With Biopsy Proven Acute Rejection at One Year Post-transplant. [One year]

Secondary Outcome Measures

1. Number of Patients Requiring Antilymphocyte Therapy for Acute Rejection. [One year]

2. Graft Survival at One Year Post-transplant [One year]

3. Incidence of Post-transplant Infections, Including, But Not Limited to, CMV Infection and Disease, BK Infection and Nephropathy, Other Opportunistic Infections, Urinary Tract Infections, Pneumonia, and Sepsis [one year]

4. Incidence of Post-transplant Malignancies, Including Post-transplant Lymphoproliferative Disease (PTLD) and Skin Cancers. [One year]

5. Incidence of Leukopenia, Defined as a Total White Blood Cell Count of Less Than 2,000 Cells/mm3 [One year]

6. Incidence of Thrombocytopenia, Defined as a Platelet Count of Less Than 100,000 Cells/mm3 [One year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female patients between 18 and 75 years of age

• Male or female patients who are primary or repeat cadaveric, living unrelated or non- Human leukocyte antigen (HLA) identical living related donor renal transplant recipients

• Female patients of child bearing potential must have a negative urine or serum pregnancy test within the past 48 hours prior to study inclusion.

• The patient has given written informed consent to participate in the study

Exclusion Criteria:

• Patient has previously received or is receiving an organ transplant other than a kidney.

• Patients who are recipients of a multiple organ transplant.

• Patient has received a primary or re-transplant from an HLA-identical living donor.

• Any positive cross-match.

• Patient is the recipient of a pediatric donor kidney from a pediatric donor aged 8 years or less.

• Patient has received an ABO incompatible donor kidney.

• Recipient or donor is known to be seropositive for hepatitis C virus (HCV) or B virus (HBV) except for hepatitis B surface antibody positive.

• Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV).

• Patient has uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives.

• Patients with thrombocytopenia (<75,000/mm3 ), with an absolute neutrophil count of < 1,000/mm3); and/or leucopoenia (< 2,000/mm3), or anemia (hemoglobin < 6 g/dL) prior to study inclusion.

• Patient is taking or has been taking an investigational drug in the 30 days prior to transplant.

• Patient has a known hypersensitivity to tacrolimus, mycophenolate mofetil, rabbit anti-thymocyte globulin, daclizumab or corticosteroids.

• Patients with severe diarrhea or other gastrointestinal disorders that might interfere with their ability to absorb oral medication.

• Patients with a history of malignancy within the last five years, except for successfully excised squamous or basal cell carcinoma of the skin.

• Patient is pregnant or lactating, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by positive human Chorionic Gonadotropin (hCG) laboratory test.

• Women of childbearing potential must use two reliable forms of contraception simultaneously, unless they are status post bilateral tubal ligation, bilateral oophorectomy, or hysterectomy. Effective contraception must be used before beginning study drug therapy, for the duration of the study and for 6 weeks following completion of the study.

• Patient has any form of substance abuse, psychiatric disorder or a condition that, in the opinion of the investigator, may invalidate communication with the investigator.

• Inability to cooperate or communicate with the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina
• Genzyme, a Sanofi Company

Investigators

• Study Chair: Kenneth D Chavin, MD,PhD, Medical University of South Carolina
• Study Chair: Nicole Pilch, PharmD, Medical University of South Carolina
• Study Chair: David Taber, PharmD, Medical University of South Carolina
• Principal Investigator: Prabhakar Baliga, MD, Medical University of South Carolina

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT00859131
• Other Study ID Numbers: thymo vs IL2
• First Posted: Mar 10, 2009
• Last Update Posted: Apr 26, 2016
• Last Verified: Feb 1, 2014

• Additional relevant MeSH terms: Kidney Failure, Chronic; Thymoglobulin; Antilymphocyte Serum; Daclizumab

Study Results

Participant Flow

Arm/Group Title	Thymoglobulin	Zenapax
Arm/Group Description	Subjects receiving Thymoglobulin as induction agent in renal transplantation Rabbit Antithymocyte globulin: 1.5 mg/kg IV pre-op, day 1, day 2, day 3, day 4	subject who will receive daclizumab or basiliximab as induction agent in renal transplantation Daclizumab: 1.0 mg/kg pre-op and 1.0 mg/kg on Day 7
Period Title: Overall Study
STARTED	102	98
COMPLETED	102	98
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Thymoglobulin	Zenapax	Total
Arm/Group Description	Subjects receiving Thymoglobulin as induction agent in renal transplantation Rabbit Antithymocyte globulin: 1.5 mg/kg IV pre-op, day 1, day 2, day 3, day 4	subject who will receive daclizumab or basiliximab as induction agent in renal transplantation Daclizumab: 1.0 mg/kg pre-op and 1.0 mg/kg on Day 7	Total of all reporting groups
Overall Participants	102	98	200
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52 (13)	49 (14)	50.2 (13.5)
Sex: Female, Male (Count of Participants)
Female	43 42.2%	36 36.7%	79 39.5%
Male	59 57.8%	62 63.3%	121 60.5%

Outcome Measures

1. Primary Outcome

Title	Treatment Efficacy Will be Defined as the Number of Patients With Biopsy Proven Acute Rejection at One Year Post-transplant.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymoglobulin	Zenapax
Arm/Group Description	Subjects receiving Thymoglobulin as induction agent in renal transplantation Rabbit Antithymocyte globulin: 1.5 mg/kg IV pre-op, day 1, day 2, day 3, day 4	subject who will receive daclizumab or basiliximab as induction agent in renal transplantation Daclizumab: 1.0 mg/kg pre-op and 1.0 mg/kg on Day 7
Measure Participants	102	98
Number [participants]	6 5.9%	10 10.2%

2. Secondary Outcome

Title	Number of Patients Requiring Antilymphocyte Therapy for Acute Rejection.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymoglobulin	Zenapax
Arm/Group Description	Subjects receiving Thymoglobulin as induction agent in renal transplantation Rabbit Antithymocyte globulin: 1.5 mg/kg IV pre-op, day 1, day 2, day 3, day 4	subject who will receive daclizumab or basiliximab as induction agent in renal transplantation Daclizumab: 1.0 mg/kg pre-op and 1.0 mg/kg on Day 7
Measure Participants	102	98
Number [Patients]	3	8

3. Secondary Outcome

Title	Graft Survival at One Year Post-transplant
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymoglobulin	Zenapax
Arm/Group Description	Subjects receiving Thymoglobulin as induction agent in renal transplantation Rabbit Antithymocyte globulin: 1.5 mg/kg IV pre-op, day 1, day 2, day 3, day 4	subject who will receive daclizumab or basiliximab as induction agent in renal transplantation Daclizumab: 1.0 mg/kg pre-op and 1.0 mg/kg on Day 7
Measure Participants	102	98
Number [participants]	101 99%	95 96.9%

4. Secondary Outcome

Title	Incidence of Post-transplant Infections, Including, But Not Limited to, CMV Infection and Disease, BK Infection and Nephropathy, Other Opportunistic Infections, Urinary Tract Infections, Pneumonia, and Sepsis
Time Frame	one year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymoglobulin	Zenapax
Arm/Group Description	Subjects receiving Thymoglobulin as induction agent in renal transplantation Rabbit Antithymocyte globulin: 1.5 mg/kg IV pre-op, day 1, day 2, day 3, day 4	subject who will receive daclizumab or basiliximab as induction agent in renal transplantation Daclizumab: 1.0 mg/kg pre-op and 1.0 mg/kg on Day 7
Measure Participants	102	98
Number [participants]	52 51%	58 59.2%

5. Secondary Outcome

Title	Incidence of Post-transplant Malignancies, Including Post-transplant Lymphoproliferative Disease (PTLD) and Skin Cancers.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymoglobulin	Zenapax
Arm/Group Description	Subjects receiving Thymoglobulin as induction agent in renal transplantation Rabbit Antithymocyte globulin: 1.5 mg/kg IV pre-op, day 1, day 2, day 3, day 4	subject who will receive daclizumab or basiliximab as induction agent in renal transplantation Daclizumab: 1.0 mg/kg pre-op and 1.0 mg/kg on Day 7
Measure Participants	102	98
Number [participants]	3 2.9%	0 0%

6. Secondary Outcome

Title	Incidence of Leukopenia, Defined as a Total White Blood Cell Count of Less Than 2,000 Cells/mm3
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymoglobulin	Zenapax
Arm/Group Description	Subjects receiving Thymoglobulin as induction agent in renal transplantation Rabbit Antithymocyte globulin: 1.5 mg/kg IV pre-op, day 1, day 2, day 3, day 4	subject who will receive daclizumab or basiliximab as induction agent in renal transplantation Daclizumab: 1.0 mg/kg pre-op and 1.0 mg/kg on Day 7
Measure Participants	102	98
Number [participants]	21 20.6%	4 4.1%

7. Secondary Outcome

Title	Incidence of Thrombocytopenia, Defined as a Platelet Count of Less Than 100,000 Cells/mm3
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymoglobulin	Zenapax
Arm/Group Description	Subjects receiving Thymoglobulin as induction agent in renal transplantation Rabbit Antithymocyte globulin: 1.5 mg/kg IV pre-op, day 1, day 2, day 3, day 4	subject who will receive daclizumab or basiliximab as induction agent in renal transplantation Daclizumab: 1.0 mg/kg pre-op and 1.0 mg/kg on Day 7
Measure Participants	102	98
Number [participants]	43 42.2%	13 13.3%

Adverse Events

Arm/Group Title	Thymoglobulin		Zenapax
Arm/Group Description	Subjects receiving Thymoglobulin as induction agent in renal transplantation Rabbit Antithymocyte globulin: 1.5 mg/kg IV pre-op, day 1, day 2, day 3, day 4		subject who will receive daclizumab or basiliximab as induction agent in renal transplantation Daclizumab: 1.0 mg/kg pre-op and 1.0 mg/kg on Day 7
All Cause Mortality
	Thymoglobulin		Zenapax
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Thymoglobulin		Zenapax
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/102 (0%)		0/98 (0%)
Other (Not Including Serious) Adverse Events
	Thymoglobulin		Zenapax
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/102 (36.3%)		44/98 (44.9%)
Blood and lymphatic system disorders
BK Viremia	13/102 (12.7%)		19/98 (19.4%)
Immune system disorders
CMV	29/102 (28.4%)		18/98 (18.4%)
Infections and infestations
Bacterial Infection	10/102 (9.8%)		21/98 (21.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.