End Stage Renal Disease (ESRD)Phase 1/2NCT01594424
A Safety Study of Tocilizumab to Improve Transplant Rates in Highly Sensitized Patients Awaiting Kidney Transplantation
A Phase 1/2 study testing Tocilizumab and Intravenous Immunoglobulin in people with End Stage Renal Disease (ESRD), run by Cedars-Sinai Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- End Stage Renal Disease (ESRD)
- What is being tested?
- Tocilizumab and Intravenous Immunoglobulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to May 2015
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- Any previous treatment with alkylating agents such as chlorambucil, (within 1 year) or with total lymphoid irradiation.
- Exclusions for General Safety:
- 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.
- Pregnant women or nursing (breast feeding) mothers.
- Patients with reproductive potential not willing to use an effective method of contraception.
- History of alcohol, drug or chemical abuse within 1 year prior to screening.
- Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation.
- Patients with lack of peripheral venous access.
- Body weight of > 150 kg.
- Laboratory Exclusion criteria (at screening):
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times upper limit of normal (ULN)
- Total Bilirubin > ULN
- Platelet count < 100 x 109/L (100,000/mm3)
- Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)
- White Blood Cells < 3.0 x 109/L (3000/mm3)
- Absolute Neutrophil Count < 2.0 x 109/L (2000/mm3)
- Absolute Lymphocyte Count < 0.5 x 109/L (500/mm3)
- Positive Hepatitis BsAg, or Hepatitis C antibody
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Medical Center
Los Angeles, California, 90048
About this study
Official title: A Phase I/II Trial of Tocilizumab + Intravenous Immunoglobulin (IVIG) as Agents to Reduce Donor-Specific Anti-HLA Antibodies (DSA) and Improve Transplant Rates in Highly-HLA Sensitized Patients Awaiting Kidney Transplantation
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)
- Being tested
- Tocilizumab, Intravenous Immunoglobulin
- Keywords
- Donor-Specific Anti-HLA Antibodies, Kidney Transplantation
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Also called Actemra®
Tocilizumab 8mg/kg on Days 0, 15, 30, 45, 75, 105, 119, 135, 149, and 180
Intravenous ImmunoglobulinDrug
Also called IVIG
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).
| Study group | Role | What they receive |
|---|---|---|
| IVIG + Tocilizumab | Experimental | Not described Receives: Drug: Tocilizumab; Drug: Intravenous Immunoglobulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Serious Infectious Complications Following Transplantation
patients will be in the study for up to 2 years
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2012 (estimated)
- Study startJun 2012
- Primary completionNov 2014
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for End Stage Renal Disease (ESRD)Studies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stanley Jordan, MD, Cedars-Sinai Medical Center
- Investigators
- Stanley Jordan, MD, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01594424
- Sponsor's protocol ID
- Actemra + IVIG
- Status last verified
- Jul 2016
- First submitted
- 4 May 2012
- Last updated
- 25 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 26018350
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of Tocilizumab + Intravenous Immunoglobulin (IVIG) as Agents to Reduce Donor-Specific Anti-HLA Antibodies (DSA) and Improve Transplant Rates in Highly-HLA Sensitized Patients Awaiting Kidney Transplantation
- ClinicalTrials.gov ID
- NCT01594424
- Acronym / sponsor ID
- Actemra + IVIG
- Conditions
- End Stage Renal Disease (ESRD)
- Keywords
- Donor-Specific Anti-HLA Antibodies, Kidney Transplantation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- Nov 2014 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 9 May 2012 (estimated)
- Results
- Posted 5 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IVIG + Tocilizumab | Experimental | Drug: Tocilizumab, Drug: Intravenous Immunoglobulin |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (31 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TocilizumabAlso: Actemra®Tocilizumab 8mg/kg on Days 0, 15, 30, 45, 75, 105, 119, 135, 149, and 180 | Drug | IVIG + Tocilizumab |
| Intravenous ImmunoglobulinAlso: IVIGAll HS who meet criteria for desensitization will receive IVIG 10% (2.0 g/kg [maximum 140 g per dose] on days 1 and 30). | Drug | IVIG + Tocilizumab |
Primary outcome
Number of Participants With Serious Infectious Complications Following Transplantation
Time frame: 24 months
patients will be in the study for up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26018350Vo 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stanley Jordan, MD principal investigator
Cedars-Sinai Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tocilizumab and Intravenous Immunoglobulin in people with End Stage Renal Disease (ESRD), run by Cedars-Sinai Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Serious Infectious Complications Following Transplantation (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01594424, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2016.