Kidney FailurePhase 1NCT02435732
CINRYZE as a Donor Pre-treatment Strategy in Kidney Recipients of KDPI>60%
A Phase 1 study testing Heparin and CINRYZE in people with Kidney Failure, run by University of Wisconsin, Madison.
Trial summary
Limiting brain death-induced organ injury through a systemic anti- inflammatory medical management should allow for improvement in the quality of transplanted organs, and as a result, clinical improvement in post-transplant outcomes represented by a decrease in the incidence of delayed graft function (DGF) after… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Kidney Failure
- What is being tested?
- Heparin and CINRYZE
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- No sites listed yet
- Study dates
- Dec 2020to May 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients receiving a kidney from a donor with KDPI>60%
- Provide written informed consent.
- Accepted for renal transplantation due to end stage renal disease (Chronic Kidney Disease Stage V).
- Recipient of a first or second renal transplant.
- For second renal transplantation, minimum 3 months since the loss of the first transplanted kidney.
- At least 18 years of age:
Show all 28Show fewer
- If female, patient must be/have:
- Post-menopausal, defined as the absence of menses for at least one year (serum FSH ≥20I U/L can also be measured according to local practice), OR Surgically sterile, defined as a bilateral tubal ligation at least 6 months prior to administration of study drug, bilateral oophorectomy, or complete hysterectomy, OR Using an effective means of contraception (per Appendix 1) that is planned to continue for the duration of the study (one year), AND negative urine pregnancy test if the patient is capable of providing a urine sample. If not capable to provide urine sample, serological pregnancy test will be perform.
- Female patients of childbearing potential who are anuric must have a serum pregnancy test.
- If male, patient must:
- Agree to use an effective means of contraception (per site-specific guidelines) that is planned to continue for the duration of the study (6 months).
- Agree not to donate sperm until 6 months after dosing.
- Patients must be willing to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations.
- Provide written informed consent.
- Accepted for liver transplantation
- Recipient of a first liver transplant.
- At least 18 years of age:
- If female, patient must be/have:
- Post-menopausal, defined as the absence of menses for at least one year (serum FSH ≥20I U/L can also be measured according to local practice), OR
- Surgically sterile, defined as a bilateral tubal ligation at least 6 months prior to administration of study drug, bilateral oophorectomy, or complete hysterectomy, OR
- Using an effective means of contraception (per Appendix 1) that is planned to continue for the duration of the study (one year), AND negative urine pregnancy test if the patient is capable of providing a urine sample. If not capable to provide urine sample, serological pregnancy test will be perform.
- Female patients of childbearing potential who are anuric must have a serum pregnancy test.
- If male, patient must:
- Agree to use an effective means of contraception (per site-specific guidelines) that is planned to continue for the duration of the study (one year).
- Agree not to donate sperm until 6 months after dosing.
- Willingness to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations.
- The criteria for enrollment in the study was originally limited to kidney donors with KDPI >85%. Over the last five years however, we have only transplanted a handful of those patients If we further restrict our patient pool to those who are not liver donors, our pool of possible donors will become even smaller, making the study very difficult, if not impossible, to complete. Furthermore, our knowledge of the pathophysiology of the complement system suggests that use of C1Inhibitor will improve liver outcomes by blunting the inflammatory response which can cause liver fibrosis and reperfusion injury. Since we have seen no negative effects on the liver in our preliminary non-human primate data, there is no need to exclude possible liver donors from our treatment.
- Therefore, in order to increase feasibility of the study, we have now expanded the trial to include donors with a KDPI above 60% (rather than > 85%), since the rate of DGF in recipients of kidneys from KDPI between 60% and 85% is similar to the group >85%. In addition, we are now including liver recipients in the study, and will consent them if the donor has a viable liver in addition to the kidney(s). If we were to only include patients with KDPI above 85%, and kidney only donors, this trial would not be feasible.
Who cannot join
- Use of an investigational drug in the 30 days before surgery.
- Participation in any other research study (drug or non-drug) without prior approval from the Medical Monitor.
- Known hypersensitivity to human monoclonal antibodies or any of the study drug excipients.
- Previous hypersensitivity to basiliximab, Campath-1H or antithymocyte globulin (ATG)
- History of or known HIV, HBV (surface antigen), or HCV positivity
- History of malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin, or cervical intraepithelial neoplasia.
Show all 20Show fewer
- Scheduled to undergo multi-organ transplantation.
- Presence of clinically significant infections requiring continued therapy.
- Positive screening for active tuberculosis.
- Existence of any surgical or medical condition, other than the current transplantation which, in the opinion of the investigator, might significantly alter the distribution, metabolism or excretion of study medication.
- History or presence of a medical condition or disease that in the investigator's assessment would place the patient at an unacceptable risk for study participation.
- Lactating or pregnant woman.
- Patient institutionalized by administrative or court order.
- HLA or ABO incompatible kidney defined as a positive cytotoxic crossmatch, positive mean fluorescent intensity beyond the acceptable parameters by the institution, or flow crossmatch-based assay that is positive (for kidney recipients only)
- Donor who is known to have received an investigational drug for I-R injury or graft rejection (immunosuppressant) in the 48H prior to organ recovery
- Participation in any other research study (drug or non-drug) without prior approval from the PI
- Donor institutionalized by administrative or court order
- Donors whose organs are allocated for transplantation to other transplant programs outside UW
- Donors for which any of the intended organ recipients has not provided consent for the study
- Donors that are donating other organs outside the scope of the study (i.e. heart, lungs, intestine) will be excluded.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Phase I, Single Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Tolerability of C1 Inhibitor (CINRYZE) as a Donor Pre-treatment Strategy in Brain Dead Donors Who Meet a Kidney Donor Risk Index (KDRI) Above 60%
Limiting brain death-induced organ injury through a systemic anti- inflammatory medical management should allow for improvement in the quality of transplanted organs, and as a result, clinical improvement in post-transplant outcomes represented by a decrease in the incidence of delayed graft function (DGF) after transplantation.
The specific aim is to evaluate the effect of C1INH (CINRYZE) as a donor pre-treatment strategy to decrease systemic inflammation and decrease the incidence of DGF in Expanded Criteria Donors (ECD), currently identified as donors with Kidney Donor Profile Index (KDPI) greater than or equal to 60%.
Read the detailed description
This is a randomized, single-center double-blinded study.
Donor Pre-treatment Strategy:
The main objective is to identify the lowest dose that will allow an at least 80% decrease in the activity of classic pathway and Mannose-Binding Lectin (MBL) pathway of complement. The main objectives parallel observations in non-human primates in which animals receiving kidneys from donors in which activity of both classic and MBL pathways of complement were reduced by at least 50% with the use of C1 inhibitors displayed very mild or no delayed graft function after transplantation.
This trial has specifically been designed to evaluate the beneficial effect of C1INH in kidneys from deceased donors which have a high rate of delayed graft function. The selection of potential donors to be part of this study will be limited to the population of donors with a KDPI over 60%.
A total of 36 brain dead donors and 72 kidney recipients will be included in the study.
Most of the donors with a Kidney Donor Profile Index (KDPI) >60%, due to the fact that they are considered "extreme" donors, are not likely to be able to donate organs other than kidneys. They would certainly not be pancreas donors, and it is unlikely they would be lung donors. There is a small possibility that donors with a KDPI >60% could be potential liver donors. In the event that a donor liver is available for transplant, we will obtain written consent from the liver recipient, as we will from the kidney recipient(s) before the donor is dosed with the CINRYZE/placebo.
For this study:
All donors will come from within our service area. All kidney and livers will be allocated to be transplanted at the UW.
Stage 1: Collection of initial safety data prior to expanding the study to a broad cohort of patients.
3 non-randomized donors: Step 1: Two kidney only donors treated with 200 units/kg C1INH and heparin at 20 units/kg/h IV maintenance until organ recovery Step 2: Two donors of both liver and kidneys, treated with 200 units/kg C1INH and heparin at 20 units/kg/h IV maintenance until organ recovery The 8 kidneys and 2 livers in Stage 1 will be allocated to be transplanted only at UW.
Stage 2: PK Study, Safety and Outcome Data
36 donors will be randomized into 3 groups:
Group 1: Control group: standard donor management + vehicle treatment (n=12) Group 2: Standard donor management + C1INH at a dose of 200 U/Kg IV single dose (n=12) Group 3: Standard donor management + C1INH at a dose of 200 units/kg IV single dose and heparin at 20 units/kg/h IV maintenance until organ recovery (n=12)
- Conditions
- Kidney Failure
- Being tested
- Placebo saline solution, Heparin, CINRYZE
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo saline solutionDrug
saline solution
HeparinDrug
Added to the one of the arms receiving 200U/kg dose of CINRYZE
CINRYZEDrug
Also called C1INH
200U/kg IV dose with or without heparin, or 500U/kg IV dose
| Study group | Role | What they receive |
|---|---|---|
| Control group | Placebo comparator | Standard donor management + vehicle treatment (n=9)- placebo saline solution Receives: Drug: Placebo saline solution |
| CINRYZE 200 U/Kg IV | Experimental | Intervention is CINRYZE 200 U/Kg IV single dose Receives: Drug: Placebo saline solution; Drug: CINRYZE |
| 200 units/kg IV CINRYZE with Heparin 20 U/kg/h IV | Experimental | CINRYZE 200 units/kg IV single dose with Heparin at 20 units/kg/h IV maintenance until organ recovery Receives: Drug: Placebo saline solution; Drug: Heparin; Drug: CINRYZE |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lowest dose that will allow at least an 80% decrease in the activity of classic pathway and MBL pathway of complement in brain death donors with KDPI over 60%, with the purpose of reducing the incidence of delayed graft function.
Assessment of graft function
Measured: over a 12 month period
Secondary outcomes (5)
Donor Pharmacokinetics: plasma concentrations and Area under the Curve (AUC) for CINRYZE
pharmacokinetics
Measured: At various timepoints within first 24 hours
Rate of of DGF in kidney transplantation from ECD brain death donors
DGF rate
Measured: Within 6 hours of brain death
Level of suppression of the classical and MBL pathways
classical and MBL pathways
Measured: Within 6 hours of brain death
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Safety and tolerability
Measured: Day of Transplant: first 24 hours, days 2-7, weeks 2,3,8, month 3, 6, 12
Levels of complement activation after brain death in donors treated with C1INH
Complement activation
Measured: Within 6 hours of brain death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2015 (estimated)
- Study startDec 2020 (estimated)
- Primary completionMay 2021 (estimated)
- Study completionMay 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney FailureStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Shire
- Responsible party
- Sponsor
- Investigators
- Luis Fernandez, MD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02435732
- Sponsor's protocol ID
- 2015-0195
- Other IDs
- A539742, SMPH/SURGERY/TRANSPLANT, Protocol Version 5/28/2018
- Status last verified
- Oct 2020
- First submitted
- 21 Apr 2015
- Last updated
- 22 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Single Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Tolerability of C1 Inhibitor (CINRYZE) as a Donor Pre-treatment Strategy in Brain Dead Donors Who Meet a Kidney Donor Risk Index (KDRI) Above 60%
- ClinicalTrials.gov ID
- NCT02435732
- Acronym / sponsor ID
- 2015-0195
- Conditions
- Kidney Failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Shire
- Study start
- Dec 2020 (estimated)
- Primary completion
- May 2021 (estimated)
- Study completion
- May 2022 (estimated)
- First posted
- 6 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Limiting brain death-induced organ injury through a systemic anti- inflammatory medical management should allow for improvement in the quality of transplanted organs, and as a result, clinical improvement in post-transplant outcomes represented by a decrease in the incidence of delayed graft function (DGF) after transplantation.
The specific aim is to evaluate the effect of C1INH (CINRYZE) as a donor pre-treatment strategy to decrease systemic inflammation and decrease the incidence of DGF in Expanded Criteria Donors (ECD), currently identified as donors with Kidney Donor Profile Index (KDPI) greater than or equal to 60%.
Detailed description
This is a randomized, single-center double-blinded study.
Donor Pre-treatment Strategy:
The main objective is to identify the lowest dose that will allow an at least 80% decrease in the activity of classic pathway and Mannose-Binding Lectin (MBL) pathway of complement. The main objectives parallel observations in non-human primates in which animals receiving kidneys from donors in which activity of both classic and MBL pathways of complement were reduced by at least 50% with the use of C1 inhibitors displayed very mild or no delayed graft function after transplantation.
This trial has specifically been designed to evaluate the beneficial effect of C1INH in kidneys from deceased donors which have a high rate of delayed graft function. The selection of potential donors to be part of this study will be limited to the population of donors with a KDPI over 60%.
A total of 36 brain dead donors and 72 kidney recipients will be included in the study.
Most of the donors with a Kidney Donor Profile Index (KDPI) >60%, due to the fact that they are considered "extreme" donors, are not likely to be able to donate organs other than kidneys. They would certainly not be pancreas donors, and it is unlikely they would be lung donors. There is a small possibility that donors with a KDPI >60% could be potential liver donors. In the event that a donor liver is available for transplant, we will obtain written consent from the liver recipient, as we will from the kidney recipient(s) before the donor is dosed with the CINRYZE/placebo.
For this study:
All donors will come from within our service area. All kidney and livers will be allocated to be transplanted at the UW.
Stage 1: Collection of initial safety data prior to expanding the study to a broad cohort of patients.
3 non-randomized donors: Step 1: Two kidney only donors treated with 200 units/kg C1INH and heparin at 20 units/kg/h IV maintenance until organ recovery Step 2: Two donors of both liver and kidneys, treated with 200 units/kg C1INH and heparin at 20 units/kg/h IV maintenance until organ recovery The 8 kidneys and 2 livers in Stage 1 will be allocated to be transplanted only at UW.
Stage 2: PK Study, Safety and Outcome Data
36 donors will be randomized into 3 groups:
Group 1: Control group: standard donor management + vehicle treatment (n=12) Group 2: Standard donor management + C1INH at a dose of 200 U/Kg IV single dose (n=12) Group 3: Standard donor management + C1INH at a dose of 200 units/kg IV single dose and heparin at 20 units/kg/h IV maintenance until organ recovery (n=12)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control group | Placebo comparator | Drug: Placebo saline solutionStandard donor management + vehicle treatment (n=9)- placebo saline solution |
| CINRYZE 200 U/Kg IV | Experimental | Drug: Placebo saline solution, Drug: CINRYZEIntervention is CINRYZE 200 U/Kg IV single dose |
| 200 units/kg IV CINRYZE with Heparin 20 U/kg/h IV | Experimental | Drug: Placebo saline solution, Drug: Heparin, Drug: CINRYZECINRYZE 200 units/kg IV single dose with Heparin at 20 units/kg/h IV maintenance until organ recovery |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Adult patients receiving a kidney from a donor with KDPI>60%
- Provide written informed consent.
- Accepted for renal transplantation due to end stage renal disease (Chronic Kidney Disease Stage V).
- Recipient of a first or second renal transplant.
- For second renal transplantation, minimum 3 months since the loss of the first transplanted kidney.
Key exclusion criteria (20 listed)
- Use of an investigational drug in the 30 days before surgery.
- Participation in any other research study (drug or non-drug) without prior approval from the Medical Monitor.
- Known hypersensitivity to human monoclonal antibodies or any of the study drug excipients.
- Previous hypersensitivity to basiliximab, Campath-1H or antithymocyte globulin (ATG)
- History of or known HIV, HBV (surface antigen), or HCV positivity
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 |
|---|---|---|
| Placebo saline solutionsaline solution | Drug | 200 units/kg IV CINRYZE with Heparin 20 U/kg/h IV, CINRYZE 200 U/Kg IV, Control group |
| HeparinAdded to the one of the arms receiving 200U/kg dose of CINRYZE | Drug | 200 units/kg IV CINRYZE with Heparin 20 U/kg/h IV |
| CINRYZEAlso: C1INH200U/kg IV dose with or without heparin, or 500U/kg IV dose | Drug | 200 units/kg IV CINRYZE with Heparin 20 U/kg/h IV, CINRYZE 200 U/Kg IV |
Primary outcome
Lowest dose that will allow at least an 80% decrease in the activity of classic pathway and MBL pathway of complement in brain death donors with KDPI over 60%, with the purpose of reducing the incidence of delayed graft function.
Time frame: over a 12 month period
Assessment of graft function
5 secondary outcomes
Donor Pharmacokinetics: plasma concentrations and Area under the Curve (AUC) for CINRYZE
Time frame: At various timepoints within first 24 hours
Rate of of DGF in kidney transplantation from ECD brain death donors
Time frame: Within 6 hours of brain death
Level of suppression of the classical and MBL pathways
Time frame: Within 6 hours of brain death
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: Day of Transplant: first 24 hours, days 2-7, weeks 2,3,8, month 3, 6, 12
Levels of complement activation after brain death in donors treated with C1INH
Time frame: Within 6 hours of brain death
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2020.
- Individual participant dataSharing planned: No
Related trials for Kidney Failure
Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
RecruitingPhase 1
Serial Amnioinfusions as Regenerative Therapy for Pulmonary Hypoplasia
Renal Failure Congenital, Congenital Renal Anomaly Nos
Recruiting
NightWare and Cardiovascular Health in Women With PTSD
Post Traumatic Stress Disorder, Cardiovascular Diseases
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
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.
Luis Fernandez, MD principal investigator
University of Wisconsin, Madison
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Heparin and CINRYZE in people with Kidney Failure, run by University of Wisconsin, Madison.
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 28 inclusion and 20 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: status not confirmed, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Luis Fernandez, MD ((608) 263-9903, luisf@surgery.wisc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lowest dose that will allow at least an 80% decrease in the activity of classic pathway and MBL pathway of complement in brain death donors with KDPI over 60%, with the purpose of reducing the incidence of delayed graft function. (time frame: over a 12 month period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Oct 2020.