DesensitizationPhase 2NCT01025193

Desensitization With Belimumab in Sensitized Patients Awaiting Kidney Transplant

A Phase 2 study testing Belimumab in people with Desensitization, run by University of Pennsylvania at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Desensitization
What is being tested?: Belimumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 8 participants
Where: 1 siteUnited States
Study dates: Feb 2010to Nov 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female patients aged 18 -75 years.
Patients denied a kidney transplant because of a prior positive crossmatch
Patients awaiting a first or second kidney transplant from a living or deceased donor
Patients who have given written informed consent to participate in all aspects of the study.
Patients with no potential living donors should have accumulated at least 12 months waiting time in our organ procurement organization
And one of the following criteria:
Pre-sensitized patients defined by Luminex antibody assays and whose panel reactive antibody (PRA) is 20% or greater
Patients with a PRA of less than 20% but who have HLA antibody specificities to HLA-Cw, DP or allele-specific antigens

Who cannot join

Patients with known hypersensitivity to belimumab or who have received biologics, within the last 90 days
Patients receiving corticosteroids, intravenous immunoglobulin, cyclophosphamide, mycophenolate mofetil, or azathioprine from 90 days prior to study entry until day of transplant.
Patients with a history of anaphylaxis to parenteral administration of contrast agents, foreign proteins, or monoclonal antibodies.
Patients with multi-organ transplant
Patients who have received any investigational immunosuppressive drug within 1 month of inclusion into this study or if use of such a product is anticipated.
Patients who have received any live vaccine within 30 days of study entry.

Show all 15Show fewer

Female patients who are pregnant, lactating.
Female patients of child bearing potential and not willing to practice an approved method of birth control for 1 month prior to the start of the study agent and 8 weeks after the last dose of study agent.
Male patients who are not agreeable to using effective contraception throughout the study and for 3 months after the last dose of study agent.
Patients with a known malignancy or history of malignancy other than excised basal or squamous cell carcinoma of the skin.
Patients who are positive for Hepatitis B infection, Hepatitis C infection or Human Immunodeficiency Virus (HIV)-positive patients.
Patients with evidence of severe liver disease, including abnormal liver profile tests > 3 times upper limit of normal at screening.
Patients with current severe infection.
Patients with any surgical or medical condition, which in the opinion of the investigator precludes enrollment in this trial
Patients who live far from the transplant center and are unable to comply with all study visits.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Pennsyvlania Kidney Transplant Program
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: One Year Exploratory Study to Evaluate the Efficacy and Safety of Belimumab for Normalization of Alloantibody Levels in Sensitized Patients Awaiting Kidney Transplantation

If subjects are listed for kidney transplant and are considered sensitized, this means they have a high amount of antibodies in their blood that could react to a kidney transplant offered for them. Antibodies are protein substances made by the body that fight anything that the body considers as a threat to it, such as infection or a kidney transplant. Sensitization may be due to prior transplants, pregnancy, or blood transfusions. Being sensitized can increase the subject's kidney transplant waiting time as it is more difficult to find a suitable kidney transplant for them that their antibodies will not react to. The purpose of this research study is to see if giving the investigational drug belimumab up to one year pre-transplant can de-sensitize the subjects, or decrease the amount of antibodies in their blood. This may help make the subjects eligible to receive a kidney transplant more quickly. If after receiving belimumab, the subjects are compatible with a donor kidney offered and are medically suitable for transplant at that time, a kidney transplant will be performed.

Read the detailed description

Approximately one third of patients awaiting kidney transplant at our transplant center have significant levels of antibodies in their blood leading to a longer wait time for a kidney transplant and death. Antibodies in the blood may be due to prior transplants, pregnancy, or blood transfusions. These antibodies sensitize a patient and make it more difficult for the patient to get a compatible kidney transplant. The measure of these antibodies is called panel reactive antibodies (PRA) and can range from 0-100%, with 100% being most sensitized. The waiting time for patients with a PRA in the range of 20%-79% is over 5 years as compared to patients with low PRA (0%-19%) which is 3-4 years. Patients with a PRA greater than 80% are likely to be granted extra points to increase the chances of transplantation. Antibodies in these patients may be due to prior transplants, pregnancy, or blood transfusions. To date, no trials with belimumab have been performed in patients with pre-existing antibodies awaiting kidney transplantation. This study is undertaken to assess the effectiveness and safety of using belimumab to normalize antibody levels in sensitized patients awaiting kidney transplantation. It is hoped that decreasing these antibodies will decrease the waiting time on the kidney transplant list, and allow the patient to become compatible with a donor kidney for transplant.

Conditions: Desensitization
Being tested: Belimumab
Keywords: belimumab, Benlysta, LymphoStat B, BLyS specific inhibitors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BelimumabDrug
Also called registered name Benlysta, also previously known as LymphoStat-B
Belimumab is a fully human monoclonal antibody that recognizes and inhibits BLyS ®. BLyS ® is a B-lymphocyte stimulator protein which plays a role in the development of B lymphocyte cells into plasma B cells, which then produce antibodies that can sensitize a potential transplant recipient. At the time of this trial, belimumab was not yet FDA approved and was being studied in clinical trials for the treatment of systemic lupus erythematosus. Until this trial, it had not yet been used in the transplant setting.

Study groups in NCT01025193
Study group	Role	What they receive
Belimumab	Experimental	Belimumab will be administered intravenously at a dose of 10mg/kg on days 0, 14, 28 and every 28 days for up to 52 weeks to normalize alloantibody levels in sensitized patients awaiting kidney transplantation. Subjects who are not able to undergo transplantation before the end of the treatment period will have final follow-up evaluation 8 weeks after the last dose of belimumab is administered. Receives: Drug: Belimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Effectiveness of Belimumab to Normalize Allo-antibody Levels in Sensitized Patients Awaiting Kidney Transplantation.
Before transplant it is necessary to measure antibodies that the recipient might have and compare them to the living or decease donor's immune make-up. Recipients with many antibodies or a specific antibody in a high concentration may have a more difficult time finding a compatible donor, and being transplanted. These recipients are referred to as sensitized patients. It is important that the sensitized recipient and the donor be compatible to prevent rejection after transplant. We measured antibodies levels in sensitized patients waiting for kidney transplant, to see if belimumab would decrease these antibody levels.
Measured: up to one year pre-transplant
Successful Kidney Transplantation From a Cross-match Compatible Donor (as a Result of Belimumab Therapy)
In order for a sensitized recipient ( a recipient with antibodies) to be transplanted, the cross match with the donor has to be compatible. We wanted to study if belimumab reduced antibodies in sensitized patients and led those patients to subsequently become cross-match compatible with a donor and allow for successful transplant.
Measured: one year pre-transplant

Secondary outcomes (5)

Pharmacokinetics of Belimumab Measured as Number of Participants With Specific Dilution Factors at Each Time Point.
We wanted to look at belimumab pharmacokinetics in sensitized patients awaiting kidney transplant. These are reported as number of participants with specific dilution factors at each studied time-point. Blood for these tests could be drawn pre dose as well as 0-4 hours after the dose was given. Belimumab dilutions factors were measured pre dose at timepoints 0 (first day of belimumab), days 56 and 364. Belimumab dilution factors were measured after the dose on days 14, and 168. Belimumab dilution factors were also measured at 8 weeks after completion of belimumab therapy and pre dose at any unscheduled visits if needed.
Measured: Belimumab serum drug dilution factors were measured in patients at at timepoints 0 (first day of belimumab), day 14, day 56, day 168, 364, at any unscheduled visits, and at 8 weeks post completion of belimumab therapy.
B and T Lymphocyte Subsets
B and T Lymphocyte subsets were measured through flow cytometry pre-treatment and at months 1,2,12 and at 8 weeks after the last belimumab dose. We looked for clinically significant changes (as determined by Principal Investigator) in these subsets at each time-point.
Measured: 8 weeks after the last dose of belimumab
BLyS Levels Before and After Treatment With Belimumab
We assessed for unexpected changes in bound and unbound BLyS levels before and after treatment with belimumab. These were measured from before treatment and at months 1,2,6,10 and 12 months after belimumab treatment and again at 8 weeks after belimumab treatment.
Measured: up to 8 weeks after completion of therapy
Hepatitis B Vaccine Antibody Titers
We investigated if belimumab treatment would decrease Hepatitis B vaccine titers by 12 months after treatment with belimumab. All patients received Hepatitis B vaccine before beginning treatment with belimumab.
Measured: up to 12 months of treatment with belimumab
Number of Participants With Treatment Related Serious Adverse Events
To assess the safety of belimumab in sensitized patients awaiting kidney transplant we evaluated the number of participants with serious adverse events possibly or definitely related to belimumab.
Measured: up to one year pre-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2010Nov 2011

First posted3 Dec 2009 (estimated)
Study startFeb 2010
Primary completionOct 2011
Study completionNov 2011

Why it stopped: has not demonstrated efficacy in primary goal

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for DesensitizationStudies of the same condition, open and under way.
More trials run by University of PennsylvaniaThe sponsor's other registered studies.
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: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: There was only one group in this trial. All participants received belimumab.
Masking: None (open label)
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01025193
Sponsor's protocol ID: IND 106342
Status last verified: May 2017
First submitted: 1 Dec 2009
Last updated: 12 Jun 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Desensitization trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: One Year Exploratory Study to Evaluate the Efficacy and Safety of Belimumab for Normalization of Alloantibody Levels in Sensitized Patients Awaiting Kidney Transplantation
ClinicalTrials.gov ID: NCT01025193
Acronym / sponsor ID: IND 106342
Conditions: Desensitization
Keywords: belimumab, Benlysta, LymphoStat B, BLyS specific inhibitors
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: has not demonstrated efficacy in primary goal
Enrolment: 8 participants (actual)
Lead sponsor: University of PennsylvaniaUniversity, hospital or other
Collaborators: Human Genome Sciences Inc.
Study start: Feb 2010
Primary completion: Oct 2011 (actual)
Study completion: Nov 2011 (actual)
First posted: 3 Dec 2009 (estimated)
Results: Posted 28 Feb 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: There was only one group in this trial. All participants received belimumab.

Arm	Type	Receives
Belimumab	Experimental	Drug: BelimumabBelimumab will be administered intravenously at a dose of 10mg/kg on days 0, 14, 28 and every 28 days for up to 52 weeks to normalize alloantibody levels in sensitized patients awaiting kidney transplantation. Subjects who are not able to undergo transplantation before the end of the treatment period will have final follow-up evaluation 8 weeks after the last dose of belimumab is administered.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Male or female patients aged 18 -75 years.
Patients denied a kidney transplant because of a prior positive crossmatch
Patients awaiting a first or second kidney transplant from a living or deceased donor
Patients who have given written informed consent to participate in all aspects of the study.
Patients with no potential living donors should have accumulated at least 12 months waiting time in our organ procurement organization

Key exclusion criteria (15 listed)

Patients with known hypersensitivity to belimumab or who have received biologics, within the last 90 days
Patients receiving corticosteroids, intravenous immunoglobulin, cyclophosphamide, mycophenolate mofetil, or azathioprine from 90 days prior to study entry until day of transplant.
Patients with a history of anaphylaxis to parenteral administration of contrast agents, foreign proteins, or monoclonal antibodies.
Patients with multi-organ transplant
Patients who have received any investigational immunosuppressive drug within 1 month of inclusion into this study or if use of such a product is anticipated.

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
BelimumabAlso: registered name Benlysta, also previously known as LymphoStat-BBelimumab is a fully human monoclonal antibody that recognizes and inhibits BLyS ®. BLyS ® is a B-lymphocyte stimulator protein which plays a role in the development of B lymphocyte cells into plasma B cells, which then produce antibodies that can sensitize a potential transplant recipient. At the time of this trial, belimumab was not yet FDA approved and was being studied in clinical trials for the treatment of systemic lupus erythematosus. Until this trial, it had not yet been used in the transplant setting.	Drug	Belimumab

Primary outcome

Effectiveness of Belimumab to Normalize Allo-antibody Levels in Sensitized Patients Awaiting Kidney Transplantation.
Time frame: up to one year pre-transplant
Before transplant it is necessary to measure antibodies that the recipient might have and compare them to the living or decease donor's immune make-up. Recipients with many antibodies or a specific antibody in a high concentration may have a more difficult time finding a compatible donor, and being transplanted. These recipients are referred to as sensitized patients. It is important that the sensitized recipient and the donor be compatible to prevent rejection after transplant. We measured antibodies levels in sensitized patients waiting for kidney transplant, to see if belimumab would decrease these antibody levels.
Successful Kidney Transplantation From a Cross-match Compatible Donor (as a Result of Belimumab Therapy)
Time frame: one year pre-transplant
In order for a sensitized recipient ( a recipient with antibodies) to be transplanted, the cross match with the donor has to be compatible. We wanted to study if belimumab reduced antibodies in sensitized patients and led those patients to subsequently become cross-match compatible with a donor and allow for successful transplant.

5 secondary outcomes

Pharmacokinetics of Belimumab Measured as Number of Participants With Specific Dilution Factors at Each Time Point.
Time frame: Belimumab serum drug dilution factors were measured in patients at at timepoints 0 (first day of belimumab), day 14, day 56, day 168, 364, at any unscheduled visits, and at 8 weeks post completion of belimumab therapy.
B and T Lymphocyte Subsets
Time frame: 8 weeks after the last dose of belimumab
BLyS Levels Before and After Treatment With Belimumab
Time frame: up to 8 weeks after completion of therapy
Hepatitis B Vaccine Antibody Titers
Time frame: up to 12 months of treatment with belimumab
Number of Participants With Treatment Related Serious Adverse Events
Time frame: up to one year pre-transplant

Results and safety

Results posted to the registry on 28 Feb 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Belimumab	8	4

Primary outcome: Effectiveness of Belimumab to Normalize Allo-antibody Levels in Sensitized Patients Awaiting Kidney Transplantation.

Time frame: up to one year pre-transplant. Count of participants. Unit: Participants

Measure	Belimumab n = 8
Patients not experiencing a decrease in antibodies	8
Patients experiencing a decrease in antibodies	0

Population analysed: any patient who received at least one dose of belimumab was included in analysis population

Primary outcome: Successful Kidney Transplantation From a Cross-match Compatible Donor (as a Result of Belimumab Therapy)

Time frame: one year pre-transplant. Count of participants. Unit: Participants

Measure	Belimumab n = 8
Kidney transplant as a result of belimumab therapy	0
kidney transplant unrelated to belimumab therapy	1
Kidney transplant not received during trial	7

Population analysed: All participants enrolled who received at least one dose of belimumab were considered for analysis.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Belimumab	3 of 8 (37.5%)	6 of 8 (75%)	Not reported

Limitations and caveats (from the sponsor): Few patients enrolled, and limited follow-up due to trial being halted due to lack of efficacy after review by investigators and the data safety monitoring board. Only one patient was transplanted during the trial (unrelated to study treatment).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Desensitization

Active, not recruitingPhase 1/2
Carfilzomib and Belatacept for Desensitization
Highly Sensitized Prospective Kidney Transplant Recipients
Not yet recruiting
Oral Immunotherapy for Children With Peanut Allergy
Peanut Allergic Subjects, Peanut Allergies
Not yet recruiting
Oral Immunotherapy for Children With Egg Allergy
Egg Allergy, Egg Hypersensitivity
Not yet recruitingPhase 2
UNC Cashew Sublingual Immunotherapy
Cashew Nut Allergy, Tree Nut Allergies
Active, not recruitingPhase 2
GRK-Biased Activation Via β2-Adrenergic Receptors in Human Skeletal Muscle
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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.

Ali Naji, MD, Ph D principal investigator

University of Pennsylvania

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 Belimumab in people with Desensitization, run by University of Pennsylvania 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 8 inclusion and 15 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: stopped early, as of the sponsor's last update on 12 Jun 2017. 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. 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?

Yes. Results are posted in the registry (first posted 28 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Effectiveness of Belimumab to Normalize Allo-antibody Levels in Sensitized Patients Awaiting Kidney Transplantation. (time frame: up to one year pre-transplant). The study lists 2 primary outcomes in all. 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 NCT01025193.

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 12 Jun 2017.