Belimumab Impacting Transplant Eligibility

NCT02500251 | Completed Phase 1

• 1 other identifier: Belimumab
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a prospective, open label, phase I/II pilot study.

Conditions

Renal Transplant Rejection

Keywords

Transplantation; belimumab; Velcade

Outcome Measures

Primary Outcomes (1)

• Efficacy of belimumab as measured by percent reduction in iDSA and/or iAb

  Maximal percent reduction in immunodominant DSA (iDSA) \[highest titer DSA (MFI)\] and/or immunodominant antibody (iAb) from pre-treatment to Day 151.

  7 months

Secondary Outcomes (1)

• Safety of belimumab as measured by toxicities and peripheral neuropathy

  7 months

Study Arms (3)

Group A (5 subjects)

EXPERIMENTAL

Subjects will receive bortezomib and plasmapheresis.

Drug: Bortezomib; Drug: Plasmapheresis

Group B (5 subjects)

EXPERIMENTAL

Subjects will receive belimumab, bortezomib, and plasmapheresis.

Drug: belimumab; Drug: Bortezomib; Drug: Plasmapheresis

Group C (5 subjects)

EXPERIMENTAL

Subjects will receive belimumab, bortezomib, rituximab, and plasmapheresis.

Drug: belimumab; Drug: Bortezomib; Drug: Rituximab; Drug: Plasmapheresis

Interventions

belimumab DRUG

Belimumab will be administered per study protocol.

Also known as: benlysta

Group B (5 subjects); Group C (5 subjects)

Bortezomib DRUG

Bortezomib will be administered per study protocol.

Also known as: Velcade

Group A (5 subjects); Group B (5 subjects); Group C (5 subjects)

Rituximab DRUG

Rituximab will be administered per study protocol.

Also known as: Rituxan

Group C (5 subjects)

Plasmapheresis DRUG

Plasmapheresis will be administered per study protocol.

Group A (5 subjects); Group B (5 subjects); Group C (5 subjects)

Eligibility Criteria

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

You may qualify if:

• Patient is between 18 and 65 years of age, inclusive, with end-stage renal disease awaiting kidney transplantation.
• Patient with eligible living donor will have: DSA against living donor of \> 5,000 MFI or a positive T or B cell flow cytometry crossmatch.
• Patient that is on the kidney transplant waiting list awaiting a deceased donor transplant and has an iAb of \> 8,000 MFI or has a current or peak calculated panel reactive antibody (cPRA) \>20%.
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Female subject is either post-menopausal for one year prior to screening or surgically sterilized. Women of childbearing potential (WOCBP) must not become pregnant and so must be sexually inactive by abstinence (starting 2 weeks prior to the 1st belimumab and/or bortezomib dose) or use contraceptive methods with a failure rate of \< 1% (starting 1 month prior to the 1st belimumab and/or bortezomib dose) for the duration of the study through 16 weeks after the last belimumab and/or bortezomib dose. WOCBP must have a negative urine or serum pregnancy test at screening and \< 7 days prior to the first belimumab and/or bortezomib dose.
• Male subjects, even if surgically sterilized (i.e., status post vasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 16 weeks after the last dose of belimumab and/or bortezomib, or completely abstain from heterosexual intercourse.
• Review of pre-transplant medical clearance by the patient's transplant nephrologist to assure the patient is medically acceptable for study entry.
• Cardiac evaluation by transplant nephrologist with clearance documented in writing to participate in the study.

You may not qualify if:

• Know hypersensitivity to bortezomib, boron or mannitol, rituximab, belimumab or any of its components.
• Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies.
• Subjects judged by the investigator to be at significant risk of failing to comply with the requirements of the protocol or unable to cooperate or communicate with the investigator.
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (Appendix A), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any abnormality on ECG performed within 30 days of consent has to be documented by the investigator or the patient's transplant nephrologist as not medically relevant.
• Patient has Grade 2 peripheral neuropathy by CTCAE criteria within 14 days before enrollment.
• Patients with an absolute neutrophil count \< 1,000/mm3 or platelet count \< 75,000/mm3 within 30 days of consent.
• Patient has received intravenous cyclophosphamide within 180 days prior to belimumab, any biologic investigational agent within 365 days prior to belimumab, or any non-biologic investigational agent within 30 days (or 5 half-lives, whichever is greater) prior to belimumab.
• Receipt of a live vaccine within 30 days prior to initiation of study treatment.
• Received blood transfusions within 30 days prior to trial entry.
• Have any intercurrent significant medical (other than renal disease) or psychiatric illness that the investigator considers would make the candidate unsuitable for the study.
• Have a historically positive HIV test or test positive for HIV within one year of consent.
• Hepatitis status:
• a. Hepatitis B: Serologic evidence of current or past Hepatitis B (HB) infection based on the results of testing for HBsAg and anti-HBc as follows: i. Patients positive for HBsAg or HBcAb historically or on testing performed within one year of consent are excluded b. Hepatitis C: Positive test for Hepatitis C antibody with a detectable viral load on testing performed within one year of consent.
• History of malignancy within the past 5 years that is not considered to be cured, with the exception of localized basal cell carcinoma of the skin (excised ≥ 2 years prior to randomization).
• Evidence of severe liver disease with abnormal liver profile (aspartate aminotransferase (AST), alanine aminotransferase (ALT) or total bilirubin \> 1.5 times upper limit of normal (ULN)) on testing performed within 30 days of consent.

Sponsors & Collaborators

• E. Steve Woodle: lead
• GlaxoSmithKline: collaborator

Study Sites (2)

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

MeSH Terms

Interventions

belimumab; Bortezomib; Rituximab; Plasmapheresis

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Blood Component Removal; Therapeutics; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• E. Steve Woodle, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Solid Organ Transplantation

Study Record Dates

• First Submitted: July 9, 2015
• First Posted: July 16, 2015
• Study Start: June 1, 2015
• Primary Completion: June 1, 2018
• Study Completion: August 1, 2018
• Last Updated: April 22, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)