Ischemia Reperfusion InjuryPhase 2YSPSLNCT00876902
YSPSL for Prevention of Ischemic Reperfusion Injury in Patients Undergoing Cadaveric Orthotopic Liver Transplantation
A Phase 2 study testing recombinant P-selectin glycoprotein ligand Ig fusion protein and Viaspan® and saline in people with Ischemia Reperfusion Injury, run by Y's Therapeutics, Inc. at 1 site in United States.
Trial summary
The study is designed to assess the feasibility of evaluating YSPSL for the amelioration of ischemia reperfusion injury following liver transplantation by administering YSPSL into the liver graft directly ex vivo via the portal vein and to the recipient intravenously prior to reperfusion. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemia Reperfusion Injury
- What is being tested?
- recombinant P-selectin glycoprotein ligand Ig fusion protein and Viaspan® and saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to Oct 2009
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient will be a recipient of a primary (first) ABO compatible cadaveric liver allograft
- Patient's age is less than 18 years
- Patient is not a recipient of a multivisceral transplant or simultaneous kidney transplant
- Patient has not undergone prior organ or cellular transplant of any type
- Patient has a Model for End Stage Liver Disease (MELD) score of ≤38
- Cold ischemia time (CIT) anticipated to be less than 14 hours
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- Donor liver procured by UCLA liver team
- Veno-veno bypass is not planned to be used for the patient (e.g. no prior surgery or other factor that indicates a risk for excessive blood loss and therefore a need for veno-veno bypass +/- autologous recovery during surgery)
- For patients who are women of childbearing potential, patient has a negative pregnancy test (either urine or serum) within 48 hours prior to transplant
- Patient (male and female) is willing to use an acceptable form of birth control for at least 3 months post-treatment
- Patient is willing and able to sign informed consent.
Who cannot join
- Patient has a prior organ transplant of any type
- Patient has known allergic or intolerance reactions to human immune globulins, antibodies, or components of the formulation or known contraindication to administration of YSPSL
- Patient has an uncontrolled active infection (on antibiotics with controlled infection is not an exclusion)
- Patient has active Hepatitis B virus (HBV)/transplant for HBV related cirrhosis
- Patient has previously participated in this study or another study with YSPSL
- Patient has received investigational therapy within 90 days prior to the transplant procedure
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- Patient has current drug or alcohol abuse or, in the opinion of the investigator, is at risk for poor compliance with the visits in this protocol (no drug testing required)
- Patient is a pregnant or nursing female, a female of childbearing potential planning to become pregnant within the duration of this study, or is not practicing birth control
- Patient is planned to receive a living donor liver transplant
- Patient lives >200 miles away or otherwise is not able to participate in study follow-up visits
- Donor body mass index >40
- Donor liver biopsy >40% macrosteatotic fat
- Donor age >70.
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA School of Medicine
Los Angeles, California, 90095
About this study
Official title: A Controlled, Prospective, Blinded, Randomized, Single-Center, Study of YSPSL for Prevention of Ischemic Reperfusion Injury in Patients Undergoing Cadaveric Orthotopic Liver Transplantation
The study is designed to assess the feasibility of evaluating YSPSL for the amelioration of ischemia reperfusion injury following liver transplantation by administering YSPSL into the liver graft directly ex vivo via the portal vein and to the recipient intravenously prior to reperfusion. This study is an extension of the recent pilot study YSPSL-0002 with an almost identical study protocol. The rationale of this and the previous study is based on the recent observation that P-selectin expression has been associated in liver grafts with prolonged cold storage times and rejection. By examining biomarkers of IRI including P-selectin by immunohistochemistry and/or quantitative PCR, liver histology and hepatic blood flow using established techniques, the goal of this study is to evaluate the feasibility of using these modalities for future studies of safety and efficacy.
Read the detailed description
YSPSL-0003 is an extension into 36 patients of the previous 12 patient pilot study YSPSL-0002 under an almost identical study protocol with extended inclusion criteria. Like YSPSL-0002, YSPSL-0003 is a single-center (UCLA), randomized, placebo-controlled, double-blind study. Patients are randomly assigned to either active study drug (Active group) or placebo (Control group) prior to transplantation. The active study drug dose includes both a 1 mg/kg IV infusion for the recipient and a 20 mg [approximately 0.27 mg/kg] as an ex vivo flush. The doses are administered via 2 separate infusions of study agent: one 20 mg dose into the portal vein of the liver prior to implantation as an ex vivo flush with Viaspan®; and the second infusion of 1 mg/kg intravenously into the recipient, when technically feasible, prior to the hepatic artery anastomosis. Placebo of a volume equivalent to active study drug is prepared for administration to the control group to help maintain the blind. Those patients that experience an intraoperative blood loss of >10 units, receive an additional 1 mg/kg IV infusion of study agent (or placebo equivalent) at the end of the transplant surgery. The Investigator/Sponsor is blinded to the treatment assignment for each patient. Randomization assignment is maintained by UCLA's clinical pharmacist.
- Conditions
- Ischemia Reperfusion Injury
- Being tested
- recombinant P-selectin glycoprotein ligand Ig fusion protein, Viaspan® and saline
- Keywords
- liver transplantation, cadaveric liver transplantation, ischemic reperfusion injury, primary non-function, delayed non-Function, poor early graft function, YSPSL, recombinant PSGL-Ig
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant P-selectin glycoprotein ligand Ig fusion proteinDrug
Also called rPSGL-Ig, Torapsel
The active study drug dose includes both a 1 mg/kg IV infusion for the recipient and a 20 mg [approximately 0.27 mg/kg] as an ex vivo flush. The doses will be administered via 2 separate infusions of study agent: one 20 mg dose into the portal vein of the liver prior to implantation as an ex vivo flush with Viaspan®; and the second infusion of 1 mg/kg intravenously into the recipient, when technically feasible, prior to the hepatic artery anastomosis. Those patients that experience an intraoperative blood loss of >10 units, will receive an additional 1 mg/kg IV infusion of study agent at the end of the transplant surgery.
Viaspan® and salineDrug
Also called Placebo
Placebo of a volume equivalent to active study drug will be prepared for administration to the control group to help maintain the blind. Those patients that experience an intraoperative blood loss of >10 units, will receive an additional 1 mg/kg IV infusion of placebo equivalent at the end of the transplant surgery.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Active Group: (18 subjects) YSPSL administered as an ex vivo flush (20 mg YSPSL in Viaspan® 200 mL total volume) into the portal vein prior to transplant at the back table; YSPSL 1 mg/kg administered IV to the transplant recipient PRIOR to arterial reperfusion of the liver. One extra IV dose of 1 mg/kg will be given at the end of the procedure only to patients that have experienced an intraoperative blood loss of greater than 10 units. Receives: Drug: recombinant P-selectin glycoprotein ligand Ig fusion protein |
| 2 | Placebo comparator | Placebo Control: (18 subjects) Ex vivo flush of placebo control (200 mL Viaspan®) into the portal vein prior to transplant and 0.1 mL/kg placebo control (saline) IV to the transplant recipient PRIOR to arterial reperfusion of the liver. One additional infusion of 0.1 mL/kg placebo control (saline) will be given at the end of the procedure to patients that have experienced an intraoperative blood loss of greater than 10 units. Receives: Drug: Viaspan® and saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety will be evaluated by clinical and laboratory assessments, an abbreviated pharmacokinetic (PK) profile of the administered dose of YSPSL, and graft function and patient and graft survival through 6 months post-transplant.
Measured: 6 months post trasplant
Secondary outcomes (1)
To evaluate the potential efficacy of prophylaxis with YSPSL on ischemia reperfusion injury (IRI) as assessed by proposed efficacy evaluations of IRI in liver transplants, in patients who meet eligibility criteria for the trial.
Measured: 6 months post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2009 (estimated)
- Study startMay 2008
- Primary completionMar 2009
- Study completionOct 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ischemia Reperfusion InjuryStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Y's Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Stefan Hemmerich, PhD, Study director, Y's Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00876902
- Sponsor's protocol ID
- YSPSL-0003-PF.3
- Other IDs
- IND 101,040
- Acronym
- YSPSL
- Status last verified
- Apr 2009
- First submitted
- 3 Apr 2009
- Last updated
- 7 Apr 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Amersi F, Farmer DG, Shaw GD, Kato H, Coito AJ, Kaldas F, Zhao D, Lassman CR, Melinek J, Ma J, Volk HD, Kupiec-Weglinski JW, Busuttil RW. P-selectin glycoprotein ligand-1 (rPSGL-Ig)-mediated blockade of CD62 selectin molecules protects rat steatotic liver grafts from ischemia/reperfusion injury. Am J Transplant. 2002 Aug;2(7):600-8. doi: 10.1034/j.1600-6143.2002.20704.x.
PubMed 12201360Busuttil RW, Lipshutz GS, Kupiec-Weglinski JW, Ponthieux S, Gjertson DW, Cheadle C, Watkins T, Ehrlich E, Katz E, Squiers EC, Rabb H, Hemmerich S. rPSGL-Ig for improvement of early liver allograft function: a double-blind, placebo-controlled, single-center phase II study. Am J Transplant. 2011 Apr;11(4):786-97. doi: 10.1111/j.1600-6143.2011.03441.x. Epub 2011 Mar 14.
PubMed 21401865
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Controlled, Prospective, Blinded, Randomized, Single-Center, Study of YSPSL for Prevention of Ischemic Reperfusion Injury in Patients Undergoing Cadaveric Orthotopic Liver Transplantation
- ClinicalTrials.gov ID
- NCT00876902
- Acronym / sponsor ID
- YSPSL / YSPSL-0003-PF.3
- Conditions
- Ischemia Reperfusion Injury
- Keywords
- liver transplantation, cadaveric liver transplantation, ischemic reperfusion injury, primary non-function, delayed non-Function, poor early graft function, YSPSL, recombinant PSGL-Ig
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Y's Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- May 2008
- Primary completion
- Mar 2009 (actual)
- Study completion
- Oct 2009 (estimated)
- First posted
- 7 Apr 2009 (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.
The study is designed to assess the feasibility of evaluating YSPSL for the amelioration of ischemia reperfusion injury following liver transplantation by administering YSPSL into the liver graft directly ex vivo via the portal vein and to the recipient intravenously prior to reperfusion. This study is an extension of the recent pilot study YSPSL-0002 with an almost identical study protocol. The rationale of this and the previous study is based on the recent observation that P-selectin expression has been associated in liver grafts with prolonged cold storage times and rejection. By examining biomarkers of IRI including P-selectin by immunohistochemistry and/or quantitative PCR, liver histology and hepatic blood flow using established techniques, the goal of this study is to evaluate the feasibility of using these modalities for future studies of safety and efficacy.
Detailed description
YSPSL-0003 is an extension into 36 patients of the previous 12 patient pilot study YSPSL-0002 under an almost identical study protocol with extended inclusion criteria. Like YSPSL-0002, YSPSL-0003 is a single-center (UCLA), randomized, placebo-controlled, double-blind study. Patients are randomly assigned to either active study drug (Active group) or placebo (Control group) prior to transplantation. The active study drug dose includes both a 1 mg/kg IV infusion for the recipient and a 20 mg [approximately 0.27 mg/kg] as an ex vivo flush. The doses are administered via 2 separate infusions of study agent: one 20 mg dose into the portal vein of the liver prior to implantation as an ex vivo flush with Viaspan®; and the second infusion of 1 mg/kg intravenously into the recipient, when technically feasible, prior to the hepatic artery anastomosis. Placebo of a volume equivalent to active study drug is prepared for administration to the control group to help maintain the blind. Those patients that experience an intraoperative blood loss of >10 units, receive an additional 1 mg/kg IV infusion of study agent (or placebo equivalent) at the end of the transplant surgery. The Investigator/Sponsor is blinded to the treatment assignment for each patient. Randomization assignment is maintained by UCLA's clinical pharmacist.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: recombinant P-selectin glycoprotein ligand Ig fusion proteinActive Group: (18 subjects) YSPSL administered as an ex vivo flush (20 mg YSPSL in Viaspan® 200 mL total volume) into the portal vein prior to transplant at the back table; YSPSL 1 mg/kg administered IV to the transplant recipient PRIOR to arterial reperfusion of the liver. One extra IV dose of 1 mg/kg will be given at the end of the procedure only to patients that have experienced an intraoperative blood loss of greater than 10 units. |
| 2 | Placebo comparator | Drug: Viaspan® and salinePlacebo Control: (18 subjects) Ex vivo flush of placebo control (200 mL Viaspan®) into the portal vein prior to transplant and 0.1 mL/kg placebo control (saline) IV to the transplant recipient PRIOR to arterial reperfusion of the liver. One additional infusion of 0.1 mL/kg placebo control (saline) will be given at the end of the procedure to patients that have experienced an intraoperative blood loss of greater than 10 units. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patient will be a recipient of a primary (first) ABO compatible cadaveric liver allograft
- Patient's age is less than 18 years
- Patient is not a recipient of a multivisceral transplant or simultaneous kidney transplant
- Patient has not undergone prior organ or cellular transplant of any type
- Patient has a Model for End Stage Liver Disease (MELD) score of ≤38
Key exclusion criteria (13 listed)
- Patient has a prior organ transplant of any type
- Patient has known allergic or intolerance reactions to human immune globulins, antibodies, or components of the formulation or known contraindication to administration of YSPSL
- Patient has an uncontrolled active infection (on antibiotics with controlled infection is not an exclusion)
- Patient has active Hepatitis B virus (HBV)/transplant for HBV related cirrhosis
- Patient has previously participated in this study or another study with YSPSL
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 |
|---|---|---|
| recombinant P-selectin glycoprotein ligand Ig fusion proteinAlso: rPSGL-Ig, TorapselThe active study drug dose includes both a 1 mg/kg IV infusion for the recipient and a 20 mg [approximately 0.27 mg/kg] as an ex vivo flush. The doses will be administered via 2 separate infusions of study agent: one 20 mg dose into the portal vein of the liver prior to implantation as an ex vivo flush with Viaspan®; and the second infusion of 1 mg/kg intravenously into the recipient, when technically feasible, prior to the hepatic artery anastomosis. Those patients that experience an intraoperative blood loss of >10 units, will receive an additional 1 mg/kg IV infusion of study agent at the end of the transplant surgery. | Drug | 1 |
| Viaspan® and salineAlso: PlaceboPlacebo of a volume equivalent to active study drug will be prepared for administration to the control group to help maintain the blind. Those patients that experience an intraoperative blood loss of >10 units, will receive an additional 1 mg/kg IV infusion of placebo equivalent at the end of the transplant surgery. | Drug | 2 |
Primary outcome
Safety will be evaluated by clinical and laboratory assessments, an abbreviated pharmacokinetic (PK) profile of the administered dose of YSPSL, and graft function and patient and graft survival through 6 months post-transplant.
Time frame: 6 months post trasplant
1 secondary outcome
To evaluate the potential efficacy of prophylaxis with YSPSL on ischemia reperfusion injury (IRI) as assessed by proposed efficacy evaluations of IRI in liver transplants, in patients who meet eligibility criteria for the trial.
Time frame: 6 months post transplant
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2009.
- Background: PubMed 12201360Amersi F, Farmer DG, Shaw GD, Kato H, Coito AJ, Kaldas F, Zhao D, Lassman CR, Melinek J, Ma J, Volk HD, Kupiec-Weglinski JW, Busuttil RW. P-selectin glycoprotein ligand-1 (rPSGL-Ig)-mediated blockade of CD62 selectin molecules protects rat steatotic liver grafts from ischemia/reperfusion injury. Am J Transplant. 2002 Aug;2(7):600-8. doi: 10.1034/j.1600-6143.2002.20704.x.
- Derived from this study: PubMed 21401865Busuttil RW, Lipshutz GS, Kupiec-Weglinski JW, Ponthieux S, Gjertson DW, Cheadle C, Watkins T, Ehrlich E, Katz E, Squiers EC, Rabb H, Hemmerich S. rPSGL-Ig for improvement of early liver allograft function: a double-blind, placebo-controlled, single-center phase II study. Am J Transplant. 2011 Apr;11(4):786-97. doi: 10.1111/j.1600-6143.2011.03441.x. Epub 2011 Mar 14.
- YSPSL (rPSGL-Ig) treatment affords benefit in animal model of liver transplantationLink provided by the sponsor.
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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.
Stefan Hemmerich, PhD study director
Y's Therapeutics, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing recombinant P-selectin glycoprotein ligand Ig fusion protein and Viaspan® and saline in people with Ischemia Reperfusion Injury, run by Y's Therapeutics, Inc. 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 11 inclusion and 13 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 7 Apr 2009. 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. 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 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?
Results are not available in the source record.
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?
Safety will be evaluated by clinical and laboratory assessments, an abbreviated pharmacokinetic (PK) profile of the administered dose of YSPSL, and graft function and patient and graft survival through 6 months post-transplant. (time frame: 6 months post trasplant). 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 NCT00876902, which also lists 2 linked publications.
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 7 Apr 2009.