The Effect and Safety Profile of Thymoglobulin® in Primary Cardiac Transplant Recipients

NCT03292861 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 1 other identifier: ATG Pilot Study
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

This is a randomized, controlled, single center study to evaluate the efficacy of Thymoglobulin induction therapy in combination with Mycophenolate Mofetil, tacrolimus, and steroids in the prevention of CAV. Approximately half of the patients will be randomized to receive a total of 5 doses of Thymoglobulin during the study. The first dose of Thymoglobulin will be administered at 1.5 mg/kg via intravenous infusion over 6 hours immediately upon arrival to the ICU post-operation (day 1). Subsequent doses of 1.5 mg/kg will be administered on days 2, 3, 4, and 5 via IV infusion over 4 hours. Mechanistic assays (T-reg cells, Lym subsets, B cell subsets, IL-1b, cytokines, TGFb, IL-21 to be drawn at Pre-transplant, 3, 6, 12 months post-transplant) will also be performed. All patients will be followed and monitored according to standard of care protocols for heart transplant recipients at our center.

Conditions

Heart Transplantation

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Composite Efficacy Failure at 12 Months

  Composite efficacy failure is defined as development of de novo donor specific antibodies (measured by standardized alloantibody testing by Luminex and control sera, characterizing kinetics, specificities and relative binding strength) and ischemia on endomyocardial biopsy (characterized on biopsy by myocyte necrosis and/or regions of myocyte dropout) at 12 months post-transplant.

  12 Months

Secondary Outcomes (29)

• Changes in immune cell profiles

  12 months

• Changes in biomarkers

  12 months

• Number of patients who experience rejection

  12 months

• Number of episodes per patient

  12 months

• First rejection by ISHLT biopsy grading scale

  12 months

Study Arms (2)

Thymoglobulin®

ACTIVE COMPARATOR

Thymoglobulin® (Genzyme) \[rabbit anti-thymocyte globulin (ATG)\] is a purified pasteurized, gamma immune globulin, obtained by immunization of rabbits with human thymocytes. This immunosuppressive product contains polyclonal cytotoxic antibodies directed against antigens expressed on human T-lymphocytes. Approximately half of the patients will be randomized to receive a total of 5 doses of Thymoglobulin during the study. The first dose of Thymoglobulin will be administered at 1.5 mg/kg via intravenous infusion over 6 hours immediately upon arrival to the ICU post-operation (day 1). Subsequent doses of 1.5 mg/kg will be administered on days 2, 3, 4, and 5 via IV infusion over 4 hours. In addition, there will be maintenance doses of mycophenolate mofetil, tacrolimus, sirolimus, and cumulative dose of corticosteroids at 12 months post-transplantation

Drug: Thymoglobulin; Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Drug: Sirolimus; Drug: Corticosteroids

No induction therapy

NO INTERVENTION

Patients qualifying for the study will be randomized before the transplantation surgery in a 1:1 ratio to either Thymoglobulin® or no treatment.

Interventions

Thymoglobulin DRUG

Approximately half of the patients will be randomized to receive a total of 5 doses of Thymoglobulin during the study. The first dose of Thymoglobulin will be administered at 1.5 mg/kg via intravenous infusion over 8 hours immediately upon arrival to the ICU post-operation (day 1). Subsequent doses of 1.5 mg/kg will be administered on days 2, 3, 4, and 5 via IV infusion over 4-8 hours.

Thymoglobulin®

Mycophenolate Mofetil DRUG

3.0 grams divided bid begun post-transplant, either IV or po as tolerated by patient. Initial dose must be given within 24 hours post-transplant. Dosing will be titrated based on recipient's body size and any adverse side effects

Thymoglobulin®

Tacrolimus DRUG

Doses of 1-4 mg bid either IV or po will be prescribed to achieve a target trough level of 10-15 ng/mL before post-operative day number 5. Target trough levels are 10-15 ng/mL for post-operative days #1-30, 8-12ng/mL days#31-60 and 5-10 ng/mL thereafter.

Thymoglobulin®

Sirolimus DRUG

Maintenance doses of sirolimus at 12 months post-transplantation

Thymoglobulin®

Corticosteroids DRUG

125 mg IV methylprednisolone immediately post-operatively x 3 doses q12hrs, then switching to oral prednisone at 1.0 mg/kg/day po divided into bid doses that are rounded off to the next higher 5 mg increment. For example, a 76 kg person would should be dosed at 38 mg po bid, which rounded off to the next 5 mg increment would be 40 mg po bid. (Equivalent dosing via an alternative route may be used if pos not tolerated or contraindicated). Prednisone will be tapered by 10 mg qd until the dose of 10 mg po bid is reached.

Thymoglobulin®

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be undergoing their first allograft transplant
• Men and non-pregnant women must be 18 to 70 years old
• Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to transplantation. The sensitivity must be equal to at least 50 mIU/mL. (Urine test is allowed in addition to serum test in patients where serum results are delayed)
• Men with a female partner of child bearing age and women of childbearing potential must use two reliable forms of contraception simultaneously. Effective contraception must be used before beginning study drug therapy, and for 4 months following discontinuation of study drug therapy.
• Subjects must be willing and capable of understanding the purpose and risks of the study, and must sign a statement of informed consent
• Subjects with a Creatinine \< 2.0 mg/dl at time of transplant

You may not qualify if:

• Allergy to Thymoglobulin-Thymoglobulin is contraindicated in patients with history of allergy or anaphylaxis to rabbit proteins or to any product excipients, or who have active acute or chronic infections which contraindicate any additional immunosuppression
• Previous organ transplants
• Patients receiving multiple organs
• Patients with a BMI higher than 35
• Patients with PRA ≥ 25%
• Patients requiring VAD upon completion of transplantation surgery.
• HIV-1, HTLV-1, chronic Hepatitis B, or chronic Hepatitis C infection
• Documented or strong suspicion for pre-operative active infection that has not yet been adequately treated with the recommended course of antimicrobial therapy
• Presence of any chronic myelosuppressive disease or agent that has resulted in either chronic leucopenia or chronic thrombocytopenia
• Active peptic ulcer disease and active GI bleeding
• Patients who have received within the past 30 days or require concomitant treatment with other investigational drugs (except for those listed in section 8.6 "Concomitant treatment")
• Patients with a history of AL amyloidosis (TTR amyloids) are permitted

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (2)

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Interventions

thymoglobulin; Mycophenolic Acid; Tacrolimus; Sirolimus; Adrenal Cortex Hormones

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Jon Kobashigawa, MD

  Director

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Advanced Heart Disease Program

Study Record Dates

• First Submitted: September 12, 2017
• First Posted: September 26, 2017
• Study Start: September 13, 2018
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

US (2)