Efficacy, Safety, Tolerability and Pharmacokinetic (PK) Study of GSK1070806 for the Prevention of Delayed Graft Function (DGF) in Adult Subjects After Renal Transplantation
Condition: Kidney Transplantation (Status Post)
MeSH terms: Delayed Graft Function
Intervention: GSK1070806; 1) basiliximab 2) mycophenolate mofetil (MMF) OR azathioprine 3) tacrolimus 4) corticosteroids
Intervention description: Injectable solution of 100 milligram/millilitre (mg/mL), administered as a single dose of 3 milligram/kilogram (mg/kg) (maximum of 10 mg/kg) diluted in 100 mL sterile IV infusion bag of 0.9% Sodium Chloride.; This immunosuppressant regimen may be revised based on the clinical judgment of the investigator including titration of tacrolimus levels.
Intervention MeSH terms: Mycophenolic Acid; Azathioprine; Tacrolimus; Basiliximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Delayed Graft Function; Renal Transplantation; Prevention; GSK1070806

Summary:

      This is a phase 2 study to evaluate the efficacy, safety, tolerability and pharmacokinetics
      of GSK1070806 in subjects undergoing renal transplantation. GSK1070806 is an anti-interleukin
      18 (IL18) monoclonal antibody, which binds to IL-18 and inhibits signaling through the IL-18
      receptor. Recipients of donor kidneys, retrieved after circulatory death of the donor, will
      be administered a single intravenous infusion of GSK1070806 to test whether inhibition of
      IL-18 can reduce the rate of Delayed Graft Function (DGF) and graft rejection. Subjects will
      be followed for 12 months post dose/transplant. Up to 40 adult subjects will be enrolled in
      this study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Recipient age range: Between 18 and 75 years of age inclusive, at the time of signing
             the informed consent.

          -  Dialysis-dependent recipient of first time, single kidney-only, Donation after
             Circulatory Death (DCD) transplant.

          -  Eligible for kidney transplantation: Considered eligible after undergoing
             multidisciplinary evaluation at the institution at which the transplantation will be
             performed.

          -  Immunosuppressants (at the time of transplantation): planned to receive a combination
             of immunosuppressants including basiliximab, mycophenolate mofetil or azathioprine,
             tacrolimus, and corticosteroids.

          -  Male and Female:

               1. Males: Male subjects with female partners of child bearing potential must utilize
                  a condom and female partners must comply with use of highly effective
                  contraceptive methods for 180 days post-dose of study medication.

               2. Females:

                    -  Non-reproductive potential defined as in the protocol. Reproductive
                       potential: Must not be pregnant or lactating, and agrees to follow one of
                       the options listed in the Modified List of Highly Effective Methods for
                       Avoiding Pregnancy in Females of Reproductive Potential (FRP) for 180 days
                       post dose as defined in the protocol.

          -  Capable of providing signed informed consent which includes compliance with the
             requirements and restrictions listed in the consent form and in the protocol.

        Exclusion Criteria:

          -  Liver function: Alanine Aminotransferase (ALT) >2xUpper Limit of Normal (ULN) and
             bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is
             fractionated and direct bilirubin <35%).

          -  QT interval: single or average Corrected QT Interval (QTc)>480 milliseconds (msec) or
             in subjects with bundle branch block QTc>500 msec (these criteria do not apply to
             subjects with predominately paced rhythms).

          -  Concurrent medication: Subjects who receive treatment that is prohibited for safety
             reasons (e.g. live vaccines, cyclophosphamide or other biologic immunosuppressants)
             should not receive investigational product without the explicit approval of the
             Medical Monitor (Sponsor).

          -  Investigational product: Any within 5 half-lives or twice the duration of the
             biological effect whichever is longer (investigational product refers to any drug not
             approved for sale in the country in which it is being used).

          -  Immunosuppression: Are being considered for steroid-free, anti-thymocyte globulin
             (ATG) or alemtuzumab induction, which have a much more profound and prolonged
             immunosuppressive effect than basiliximab.

          -  Prior biologic immunosuppressives: The subject has received an agent within the
             following time period prior to the day of dosing in the current study: 30 days, 5
             half-lives or twice the duration of the biological effect, whichever is longer.

          -  Vaccines: A live vaccine within 30 days prior to GSK1070806 administration

          -  Receiving a DCD kidney allograft from a donor with any of the following
             characteristics: cold ischemic time >36 hours, age <5 years old, age >75 years old,
             ABO blood type incompatible against the recipient, T- and/or B-cell positive
             cross-match by complement dependent cytotoxicity or flow cytometry against the
             recipient (where positive cross-match is unavailable, virtual cross-match is allowed),
             serology positive for hepatitis B (except hepatitis B surface antibody and prior
             vaccination), hepatitis C or human immunodeficiency virus (HIV), Epstein Barr Virus
             (EBV) positive donor allograft with an EBV negative recipient, donor had acute or
             chronic bacterial, viral or fungal infection that according to the investigator causes
             a risk to recipient, particularly if the infection was resistant or systemic,
             normothermic regional machine perfusion organ retrieval techniques were utilized,
             surgical damage to donor allograft during organ procurement

          -  Previous organ transplantation: has previously undergone any other organ
             transplantation (with the exception of corneal transplantation).

          -  Malignancy: has a history of malignancy in the past 5 years except for adequately
             treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the
             uterine cervix.

          -  Acute or chronic infection: has required management of acute or chronic infections
             (excludes prophylaxis of infections), as follows: currently being treated for a
             chronic infection, which in the opinion of the investigator, could put the subject at
             undue risk; hospitalized for treatment of infection, or treated for an infection with
             parenteral antibiotics (includes antibacterials, antivirals, anti-fungals, or
             anti-parasitic agents) within 30 days before Day 0, which in the opinion of the
             investigator, could put the subject at undue risk; current evidence, or history within
             the last 14 days, of an influenza-like illness as defined by fever (>38 degree
             Celsius) and two or more of the following symptoms: cough, sore throat, runny nose,
             sneezing, limb / joint pain, headache, vomiting / diarrhoea; subjects with any history
             of active tuberculosis, recent tuberculosis exposure, or judged by investigators to be
             at risk of tuberculosis will be excluded from the study.

          -  Other disease/conditions. Has any of the following: clinical evidence of significant
             unstable or uncontrolled acute or chronic diseases, which in the opinion of the
             investigator, could confound the results of the study or put the subject at undue
             risk; a surgical procedure planned in the 12 months after Day 0, other than kidney
             transplantation or related procedure; a known history of any other medical disease
             (e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous
             access) that, in the opinion of the investigator, makes the subject unsuitable for the
             study

          -  Hepatitis B: subjects will be excluded with any evidence of acute or chronic
             infection, or if interpretation of their results is unclear. This includes: Hepatitis
             B surface Antigen (HBsAg)+, Anti- Hepatitis B core (Anti-HBc)+, Hepatitis B
             Deoxyribose Nucleic Acid (HB DNA)+. It is permissible to enroll subjects who are
             anti-Hepatitis B (HB)s+ only, when this is attributable to vaccination and there is no
             history of previous infection.

          -  Hepatitis C: subjects will be excluded if there is any evidence of past or current
             hepatitis C infection, including hepatitis C antibody, hepatitis C Recombinant
             ImmunoBlot Assay (RIBA) or Polymerase Chain Reaction (PCR).

          -  HIV: known to have a historically positive HIV test.

          -  Immunodeficiency: recipient with a history of, or laboratory evidence of
             immunodeficiency.

          -  Drug Sensitivity: has a history of sensitivity to any of the study medications
             including: GSK1070806; background immunosuppressive regimen; designated prophylactic
             anti-infective therapies or components thereof, or a history of drug or other allergy
             including a previous anaphylactic reaction to parenteral administration or biologic
             therapy (ie monoclonal antibody) that, in the opinion of the Investigator or Medical
             Monitor, contraindicates their participation.

          -  Substance abuse: has clinical evidence of current drug or alcohol abuse or dependence.

          -  Co enrollment: participating in another interventional study (participation in purely
             observational or cohort studies is acceptable provided they do not impair feasibility,
             or involve excessive additional sampling).

          -  Compliance: is unlikely to comply with scheduled study visits based on investigator
             judgment or has a history of a psychiatric disorder or condition that may compromise
             communication with the investigator.