A Safety Study of Tocilizumab to Improve Transplant Rates in Highly Sensitized Patients Awaiting Kidney Transplantation

NCT01594424 | Completed Phase 1 Results DMC

• 1 other identifier: Actemra + IVIG
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

In this Phase I/II trial, 10 highly sensitized patients will be entered after informed consent and will receive Intravenous Immunoglobulin (IVIG) at 2 gm/kg + Tocilizumab 8 mg/kg x 5 doses on days 15, 45, 75, 105, 119, 135, and 149. If robust reductions in anti-HLA antibody are seen, patients will progress to kidney transplantation when an "acceptable" crossmatch is achieved with a living donor (LD) or deceased donor (DD). Those receiving transplants will also receive Tocilizumab infusion monthly X7 doses post-transplant. All subjects will have intensive monitoring of Donor Specific Antibodies (DSA), viral PCRs, and routine post-transplant labs. At 6 months post-transplant, those who have retained their transplanted kidney will have a protocol biopsy.

Conditions

End Stage Renal Disease (ESRD)

Keywords

Donor-Specific Anti-HLA Antibodies; Kidney Transplantation

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Serious Infectious Complications Following Transplantation

  patients will be in the study for up to 2 years

  24 months

Study Arms (1)

IVIG + Tocilizumab

EXPERIMENTAL

Drug: Tocilizumab; Drug: Intravenous Immunoglobulin

Interventions

Tocilizumab DRUG

Tocilizumab 8mg/kg on Days 0, 15, 30, 45, 75, 105, 119, 135, 149, and 180

Also known as: Actemra®

IVIG + Tocilizumab

Intravenous Immunoglobulin DRUG

All HS who meet criteria for desensitization will receive IVIG 10% (2.0 g/kg \[maximum 140 g per dose\] on days 1 and 30).

Also known as: IVIG

IVIG + Tocilizumab

Eligibility Criteria

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

You may qualify if:

• End-stage renal disease.
• No known contraindications for therapy with IVIG 10%/Actemra®.
• Age 18-65 years at the time of screening.
• CPRA \> 50% demonstrated on 3 consecutive samples, UNOS wait time sufficient to allow DD offers, history of sensitizing events, positive crossmatch with the intended donor. LDs with DSA and Crossmatch positivity.
• Subject/Parent/Guardian must be able to understand and provide informed consent.

You may not qualify if:

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
• 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 within 6 months of baseline.
• Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline
• Immunization with a live/attenuated vaccine within 2 months 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, (within 1 year) or with total lymphoid irradiation.
• 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), hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated 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). These are limited to non-access related infections.
• Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening.
• Active TB requiring treatment within the previous 3 years. Patients should be screened for latent TB and, if positive, treated following local practice guidelines prior to initiating TCZ. Patients treated for tuberculosis with no recurrence in 3 years are permitted.
• Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation.
• Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including hematological malignancies and solid tumors, except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 20 years unless related to primary disease under investigation.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Related Publications (1)

• Vo AA, Choi J, Kim I, Louie S, Cisneros K, Kahwaji J, Toyoda M, Ge S, Haas M, Puliyanda D, Reinsmoen N, Peng A, Villicana R, Jordan SC. A Phase I/II Trial of the Interleukin-6 Receptor-Specific Humanized Monoclonal (Tocilizumab) + Intravenous Immunoglobulin in Difficult to Desensitize Patients. Transplantation. 2015 Nov;99(11):2356-63. doi: 10.1097/TP.0000000000000741.

  PMID: 26018350 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

tocilizumab; Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jua Choi, PharmD
• Organization: Cedars-Sinai Medical Center, Comprehensive Transplant Center

jua.choi@cshs.org

310-248-8186

Study Officials

• Stanley Jordan, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Medical Director, Renal Transplantation & Transplant Immunotherpay

Study Record Dates

• First Submitted: May 4, 2012
• First Posted: May 9, 2012
• Study Start: June 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: May 1, 2015
• Last Updated: August 25, 2016
• Results First Posted: August 5, 2015

Record last verified: 2016-07

Locations

US (1)