Tocilizumab for Renal Graft Inflammation

NCT02108600 | Completed Phase 2 Results DMC

• 1 other identifier: ML29092
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized open label clinical trial in which 48 renal transplant recipients with inflammation in the 6 month allograft biopsy will either continue usual immunosuppression or receive monthly Actemra (Tocilizumab) infusions for 6 months in addition to usual immunosuppression.

Conditions

Late Complication From Kidney Transplant

Keywords

Kidney transplantation; Inflammation

Outcome Measures

Primary Outcomes (1)

• Change in Inflammation on Renal Allograft Biopsy From Baseline to 6 Months

  Proportion of participants in each group who had a 1 point decrease in inflammation based on Banff scoring on renal allograft biopsy at 6 months compared to baseline. The Banff ti- score can be 0, 1, 2 or 3.

  Baseline and 6 months

Secondary Outcomes (3)

• Change in Urinary Cytokines

  Baseline and 6 months

• Development of Donor Specific Anti-HLA Antibodies

  From baseline to 6 months

• Incidence of Acute Rejection

  In the interval between baseline and 6 Months

Study Arms (2)

Standard of Care

NO INTERVENTION

Will continue usual immunosuppression and not receive any specific intervention.

Tocilizumab (TCZ) Group

EXPERIMENTAL

Will receive tocilizumab 8 mg/kg intravenously at four-week intervals for a total of 6 doses. In addition, will continue usual immunosuppressive regimen.

Drug: Tocilizumab

Interventions

Tocilizumab DRUG

Will receive tocilizumab 8 mg/kg intravenously at four-week intervals for a total of 6 doses. In addition, will continue usual immunosuppressive regimen.

Tocilizumab (TCZ) Group

Eligibility Criteria

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

You may qualify if:

• All kidney transplant recipients with SCI on 6-month surveillance biopsy.
• Maintenance immunosuppression regimens containing tacrolimus and MMF with or without prednisone.
• Ability to provide written informed consent for the study.
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.

You may not qualify if:

• General:
• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
• Excluded Previous or Concomitant Therapy:
• Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening.
• Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20, except Thymoglobulin.
• Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline.
• Immunization with a live/attenuated vaccine within 4 weeks prior to baseline.
• Previous treatment with TCZ (an exception to this criterion may be granted for single dose exposure upon application to the sponsor on a case-by-case basis).
• Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
• Presence of acute cellular (Banff Type 1-3) or antibody-mediated rejection on 6-month surveillance biopsy or on biopsies for-cause in the previous 6 months.
• History of positive urine or serum screening for BK virus (defined as a quantitative BK virus PCR in urine \> 0.5 million copies/ml or any detectable BK viremia) within the first 6 months post-transplant.
• History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.
• Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including diverticulitis, ulcerative colitis, or Crohn's disease.)
• Current liver disease as determined by principal investigator unless related to primary disease under investigation.
• Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds).

Sponsors & Collaborators

• Flavio Vincenti: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (5)

• Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant. 2004 Mar;4(3):378-83. doi: 10.1111/j.1600-6143.2004.00332.x.

  PMID: 14961990 BACKGROUND

• Nankivell BJ, Fenton-Lee CA, Kuypers DR, Cheung E, Allen RD, O'Connell PJ, Chapman JR. Effect of histological damage on long-term kidney transplant outcome. Transplantation. 2001 Feb 27;71(4):515-23. doi: 10.1097/00007890-200102270-00006.

  PMID: 11258430 BACKGROUND

• Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med. 2003 Dec 11;349(24):2326-33. doi: 10.1056/NEJMoa020009.

  PMID: 14668458 BACKGROUND

• Cosio FG, Grande JP, Larson TS, Gloor JM, Velosa JA, Textor SC, Griffin MD, Stegall MD. Kidney allograft fibrosis and atrophy early after living donor transplantation. Am J Transplant. 2005 May;5(5):1130-6. doi: 10.1111/j.1600-6143.2005.00811.x.

  PMID: 15816896 BACKGROUND

• Chandran S, Leung J, Hu C, Laszik ZG, Tang Q, Vincenti FG. Interleukin-6 blockade with tocilizumab increases Tregs and reduces T effector cytokines in renal graft inflammation: A randomized controlled trial. Am J Transplant. 2021 Jul;21(7):2543-2554. doi: 10.1111/ajt.16459. Epub 2021 Jan 21.

  PMID: 33331082 RESULT

MeSH Terms

Conditions

Inflammation

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The study could not meet its recruitment target of 48 subjects, and consequently, is underpowered statistically. Additionally, the urine samples were inadequate, leading to inability to perform urine cytokine measurements.

Results Point of Contact

• Title: Sindhu Chandran
• Organization: University of California, San Francisco

sindhu.chandran@ucsf.edu

4153538374

Study Officials

• Flavio Vincenti, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: March 27, 2014
• First Posted: April 9, 2014
• Study Start: June 1, 2014
• Primary Completion: December 16, 2018
• Study Completion: December 16, 2018
• Last Updated: March 9, 2021
• Results First Posted: January 27, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)