Efficacy and Safety of Human Plasma-derived C1-esterase Inhibitor as add-on to Standard of Care for the Treatment of Refractory Antibody Mediated Rejection (AMR) in Adult Renal Transplant Recipients

Overview

  • Study type

    Interventional
  • Study phase

    III
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Scottsdale/Phoenix, Arizona: 18-005462
    • Rochester, Minnesota: 18-005462
    NCT ID: NCT03221842
    Sponsor Protocol Number: CSL842_3001

About this study

The purpose of this double-blind, randomized-withdrawal, placebo-controlled study in kidney transplant patients with AMR is to evaluate the efficacy and safety of human plasma-derived C1-esterase inhibitor as add-on to standard of care (IVIG).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • Provide written informed consent and willing and able to adhere to all protocol requirements.
  • At least 18 years of age at the time of providing written informed consent.
  • Evidence of at least one DSA (to HLA class I and/or class II)
  • Recipient of a kidney transplant from an ABO compatible or ABO incompatible donor, living or deceased.
  • At least one of the following:
    • Achieved a steady-state, post-transplant eGFR ≥ 40 mL/min/1.73 m2 (as determined by local practice) within 60 days post-transplant; OR
    • A 50% increase in urine output with a 50% decrease in serum creatinine over the first 7 days post-transplant in subjects with slow or delayed graft function.
  • Acute AMR on pre-enrollment kidney biopsy, defined per Banff 2015 criteria [Loupy et al, 2017] as the following:
    • Histologic evidence of acute tissue inflammation with presence of neutrophils and/or monocytes (g > 0, v > 0, and/or ptc > 0); AND
    • C4d positive or, if C4d negative, then g + ptc ≥ 2.
    • NOTE: Subjects who have mixed cellular rejection with AMR are eligible for participation.
  • Acute AMR that is unresponsive (ie, no improvement in renal function as determined by the treating physician) after standard of care treatment, where standard of care treatment is 1 of the following:
    • ≥ 7 days since the current AMR diagnosis, if standard of care treatment is ≥ 100 mg/kg IVIg and plasmapheresis, with or without rituximab, at the Day 1 Visit; OR
    • ≤ 45 days since the current AMR diagnosis, if standard of care treatment is > 1 gram/kg IVIg without plasmapheresis, with or without rituximab, at the Day 1 Visit.
  • Subject must be willing and able to comply with the requirements of the study protocol.
  • Investigator believes that the subject understands the nature, scope and possible consequences of the study.

Exclusion Criteria: 

  • Recipient of an en bloc kidney transplant.
  • Ongoing dialysis > 2 weeks at Screening.
  • Hepatobiliary disease as indicated by 1 of the following:
    • Viral hepatitis ie, positive for HCV or HBV confirmed by nucleic acid testing (if positive, subjects must be receiving or have received antiviral therapy and have no history of cirrhosis);OR
    • Alanine aminotransferase > 3 times upper limit of normal; OR
    • Total bilirubin > 1.5 times upper limit of normal.
  • History of human immunodeficiency virus with acquired immunodeficiency syndrome at Screening.
  • Active bacterial or fungal infection that is clinically significant in the opinion of the investigator.
  • Not otherwise explained thrombotic microangiopathy on pre-enrollment kidney biopsy.
  • Known congenital bleeding or coagulopathy disorder.
  • Evidence of non-catheter related deep vein thrombosis, stroke, myocardial infarction, or arterial embolus within the 3 months before the Day 1 Visit; catheter-related thrombosis or history of clotting a dialysis access is NOT exclusionary, in the absence of an established hereditary coagulopathy.
  • Treatment with a complement inhibitor (e.g., Soliris [eculizumab], Berinert [C1-INH], Cinryze [C1-INH]), or experimental therapies for the treatment of AMR other than IVIg or rituximab (eg, bortezomib) within 14 days before administration of C1-INH at the Day 1 Visit.
  • Current cancer or a history of cancer within 2 years before providing informed consent, with the exception of successfully treated non-metastatic basal or squamous cell carcinoma of the skin, in situ breast or other in situ lesions considered cured by therapy.
  • Any medical condition that, in the opinion of the investigator, might interfere with the subject participation in the study, poses an added risk to the subject, or confounds the assessment of the subject.
  • Female subjects who are pregnant (as evidenced by a positive serum pregnancy test for choriogonadotropin beta at Screening) or breast feeding.
  • Female subject of childbearing potential or male subject not using or not willing to use a medically reliable method of contraception from the first dose of investigational product in any treatment period until 1 month after the last dose of investigational product in the same treatment period.
  • Participation in another interventional clinical study for AMR at Screening; subject may have been withdrawn from an AMR study at any time before Screening.
  • Known or suspected hypersensitivity to the investigational product (ie, C1-INH or placebo), to any excipients of the investigational product, or to any other C1-esterase inhibitor preparation (eg, Berinert) or albumin preparation.
  • Involved in the planning and/or conduct of the study (applies to CSL staff, staff at the study site, and third-party vendors).

 

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Hasan Khamash, M.D.

Open for enrollment

Contact information:

Neena Abraham M.D., M.S.

7916990

Abraham.Neena@mayo.edu

Rochester, Minn.

Mayo Clinic principal investigator

Hasan Khamash, M.D.

Contact us for the latest status

Contact information:

Leah Majerus

127or7753940

Majerus.Leah@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20441689

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