RUCONEST® as a Therapeutic Strategy to Reduce the Incidence of Delayed Graft Function

NCT03791476 | Unknown Phase 1 DMC FDA Drug

• 4 other identifiers: 2017-1325A539742SMPH/SURGERY/TRANSPLANTProtocol Version 12/26/2019
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

An unmet medical need exists for therapeutic regimens in transplantation that allow immediate postoperative graft function, thereby improving graft survival. Delayed graft function (DGF) after transplantation is the most common complication affecting kidney allographs in the immediate transplant period. The specific aim of this study is to evaluate the effect of recombinant human C1-inhibitor (rhC1INH), as a kidney recipient intra- and post operative treatment strategy to decrease systemic inflammation and decrease the incidence of DGF from donation after cardiac death donors (DCD).

Conditions

Kidney Failure

Keywords

Delayed graft function

Outcome Measures

Primary Outcomes (1)

• Number of patients that do not meet DGF criteria based on creatinine levels following kidney transplantation from DCD donor who are treated with study drug compared to placebo

  Incidence of delayed graft function in the first 7 days following kidney transplant as defined as the initiation of dialysis in the first 7-days post transplantation and functional DGF as defined as a failure of the serum creatinine to decrease by at least 10% daily on 3 successive days during the first week post transplantation.

  over a 12 month period

Secondary Outcomes (8)

• Incidence of adverse and serious adverse events will be assessed via descriptive statistics method

  over a 12 month period

• Ascertain whether any unexpected toxicities will occur in this patient population according to the Common Toxicity Criteria for Adverse Events (CTCAE) patient population

  over a 12 month period

• Willingness of participation will be evaluated based on number of potential study candidates (approaches) compared to the number of candidates that enroll in the study likely response rates

  over a 12 month period

• Tolerability following drug administration as measured by blood pressure

  over a 12 month period

• Tolerability following drug administration as measured by HR (heart rate)

  over a 12 month period

Study Arms (2)

Control Group

PLACEBO COMPARATOR

Intervention is saline solution placebo (0.9% Sodium Chloride IV to equal volume of investigational arm: intraoperatively, and then every 12 hours x 2 = total of 3 doses)

Other: Saline Solution

rhC1INH

EXPERIMENTAL

Intervention is rhC1INH 100 U/kg intraoperative followed by 50 U/kg every 12 hours x 2 = total of 3 doses (200 U/kg)

Drug: rhC1INH

Interventions

rhC1INH DRUG

C1 esterase inhibitor

Also known as: ruconest

rhC1INH

Saline Solution OTHER

saline solution

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients receiving a transplanted kidney should satisfy the following to be considered part of the study:
• Has the ability to understand the requirements of the study, is able to provide written informed consent (including consent for the use and disclosure of research related health information).
• Male or female at least 18 years of age.
• Is to be a recipient of a transplant from a deceased donor (donation after cardio-circulatory determination of death criteria).
• Is able to comply with standard of care induction therapy requirement, such as antibody induction therapy with rabbit polyclonal anti-thymocyte globulin,anti-CD25 (anti-IL2R), or Anti-CD52.
• A female subject is eligible to enter the study if she is:
• Not pregnant or nursing
• Of non-childbearing potential (i.e., post-menopausal defined as having been amenorrheic for at least 1 year prior to screening, or has had a bilateral tubal ligation at least 6 months prior to administration of study drug or bilateral oophorectomy or complete hysterectomy).
• If of childbearing potential, must have a negative serum pregnancy test within 48 hours prior to transplant surgery and be using an effective means of contraception (per the site-specific guidelines or using 2 methods of birth control concurrently, whichever is more stringent) which will be continued until the Day 180 visit.
• Male subjects with female partners of childbearing potential must agree to use an effective means of contraception (per the site-specific guidelines or use 2 methods of birth control concurrently, whichever is more stringent), which will be continued until the Day 180 visit. They will also agree not to donate sperm until 6 months after dosing.
• Must be up-to-date on cancer screening according to site-specific guidelines and past medical history must be negative for biopsy-confirmed malignancy within 5 years of randomization, with the exception of adequately treated basal cell or squamous cell carcinoma in situ or carcinoma of the cervix in situ.
• Must be willing to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations.

You may not qualify if:

• 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 sponsor investigator.
• Recipient of a live donor kidney or a kidney from a brain death donor (DBD) donor.
• Recipient of donor kidney preserved with normothermic machine perfusion.
• Scheduled to undergo multiorgan transplantation.
• Has a planned transplant of kidneys that are implanted en-bloc (dual kidney transplantation).
• Has planned transplant of dual kidneys (from the same donor) transplanted not en-bloc.
• Has lost first kidney transplant due to graft thrombosis.
• Is scheduled for transplantation of a kidney from a donor who is known to have received an investigational therapy under another IND/CTA for ischemic/reperfusion injury immediately prior to organ recovery.
• 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 malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin, or cervical intraepithelial neoplasia.
• HIV positive recipients.
• Hepatitis B surface antigen positive kidney transplant recipients.
• Hepatitis B core antibody positive kidney transplant recipients.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Pharming Technologies B.V.: collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53792, United States

RECRUITING

Related Publications (69)

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• Damman J, Kok JL, Snieder H, Leuvenink HG, van Goor H, Hillebrands JL, van Dijk MC, Hepkema BG, Reznichenko A, van den Born J, de Borst MH, Bakker SJ, Navis GJ, Ploeg RJ, Seelen MA. Lectin complement pathway gene profile of the donor and recipient does not influence graft outcome after kidney transplantation. Mol Immunol. 2012 Feb;50(1-2):1-8. doi: 10.1016/j.molimm.2011.11.009. Epub 2011 Dec 15.

  PMID: 22173059 BACKGROUND

• Heijnen BH, Straatsburg IH, Padilla ND, Van Mierlo GJ, Hack CE, Van Gulik TM. Inhibition of classical complement activation attenuates liver ischaemia and reperfusion injury in a rat model. Clin Exp Immunol. 2006 Jan;143(1):15-23. doi: 10.1111/j.1365-2249.2005.02958.x.

  PMID: 16367929 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency; Delayed Graft Function

Interventions

conestat alfa; Saline Solution

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Luis Fernandez

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luis Fernandez, MD

CONTACT

608-263-9903; luis@surgery.wisc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Intervention versus placebo

Study Record Dates

• First Submitted: July 12, 2018
• First Posted: January 2, 2019
• Study Start: June 21, 2019
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: December 14, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)