Antibody-mediated RejectionPhase 2NCT01895127
Efficacy and Safety of Eculizumab for Treatment of Antibody-mediated Rejection Following Renal Transplantation
A Phase 2 study testing Eculizumab, Immunoglobulin and Plasmapheresis in people with Antibody-mediated Rejection and Humoral Rejection, run by Brigham and Women's Hospital at 3 sites in United States.
Trial summary
This is an open-label analysis that will compare eculizumab versus Plasmapheresis (PP) and Immunoglobulin (IVIg) for the treatment of antibody-mediated rejection (AMR) in renal transplant recipients. All patients will be evaluated from the time of AMR diagnosis for 12 months. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Antibody-mediated Rejection, Humoral Rejection
- What is being tested?
- Eculizumab, Immunoglobulin and Plasmapheresis
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2013to Apr 2016
- 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
- Adult renal transplant recipients, men and women between 18 and 75 years of age.
- Any patient with acute graft dysfunction (elevation of creatinine above post transplant nadir)
- AND, two out of three, of the following Inclusion Criteria:
- Presence of circulating anti human leukocyte antigen (HLA) antibody (DSA "donor specific antibody").
- Histological findings compatible with Banff Class II or III AMR on transplant biopsy.
- Peritubular capillary c4d positivity on transplant biopsy.
Who cannot join
- Patients that have received eculizumab prior to enrolling in the study.
- Patients with ongoing non-acute antibody mediated rejection.
- Patients with predominantly chronic antibody mediated rejection or interstitial fibrosis/tubular atrophy.
- History of severe cardiac disease (e.g., New York Heart Association [NYHA] Functional Class III or IV, myocardial infarction ≤ 6 months of randomization, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases)
- Prior splenectomy
- Has a known bleeding disorder
Show all 18Show fewer
- Has any active bacterial or other infection which is clinically significant in the opinion of the Investigator and is a contraindication to transplantation
- Has participated in any other investigational drug study or was exposed to an investigational drug or device within 30 days of screening
- Has received rituximab (Rituxan®) ≤ 3 months prior to screening
- Has received bortezomib (Velcade®) ≤ 3 months prior to screening
- Has received alemtuzumab (Campath®) ≤ 6 months prior to screening
- Need for concurrent treatment with anti thymocyte globulin (Thymoglobulin®)
- Hypersensitivity to murine proteins or to one of the product excipients
- History of illicit drug use or alcohol abuse within the previous year
- Unresolved meningococcal disease
- Pregnancy or lactation
- Current cancer or a history of cancer within the 5 years prior to screening with the exception of patients who have successfully treated non-metastatic basal or squamous cell carcinoma of the skin; carcinoma in situ of the cervix; or breast carcinoma in situ
- Any medical condition that, in the opinion of the Investigator, might interfere with the patient's participation in the study, poses an added risk for the patient, or confounds the assessment of the patient Active infection with Hepatitis B (HBV), Hepatitis C (HCV) or human immunodeficiency virus (HIV)
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Michigan Medical Center
Ann Arbor, Michigan, 48109
Brigham and Women's Hospital
Boston, Massachusetts, 02115
UCSF Medical Center
San Francisco, California, 94122
About this study
Official title: Efficacy and Safety of Eculizumab for Treatment of Antibody-mediated Rejection Following Renal Transplantation.
This is an open-label analysis that will compare eculizumab versus Plasmapheresis (PP) and Immunoglobulin (IVIg) for the treatment of antibody-mediated rejection (AMR) in renal transplant recipients. All patients will be evaluated from the time of AMR diagnosis for 12 months.
- Conditions
- Antibody-mediated Rejection, Humoral Rejection
- Being tested
- Eculizumab, Immunoglobulin, Plasmapheresis
- Keywords
- Kidney Transplant, Renal Transplant, Rejection, Antibody mediated, Humoral, Eculizumab
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EculizumabDrug
Also called Soliris
ImmunoglobulinBiological
Also called IVIg
PlasmapheresisProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care | Active comparator | * Plasmapheresis (PP) x 3, at 40-60 cc/kg.
* Immunoglobulin (IVIg), to be administered after each PP Receives: Biological: Immunoglobulin; Procedure: Plasmapheresis |
| Soliris (eculizumab) | Experimental | * 1200 mg first dose (Time: Screening/Week "0", after Biopsy Proven AMR)
* 900 mg weekly for 4 doses (Weeks 1, 2, 3, 4)
* 1200 mg week 5
* Week 6: If donor specific antibody < 50% of baseline DSA then no further treatment, otherwise 1200 mg weeks 7, 9 Receives: Drug: Eculizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Estimated Glomerular Filtration (eGFR) Rate
Percent change in eGFR rate at 3 months post-treatment using the modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
Measured: Month 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2013 (estimated)
- Study startNov 2013
- Primary completionApr 2016
- Study completionApr 2016
Why it stopped: Lack of efficacy
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 Antibody-mediated RejectionStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Anil K. Chandraker, MD, Brigham and Women's Hospital
- Investigators
- Anil K Chandraker, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01895127
- Sponsor's protocol ID
- 2013P001292
- Status last verified
- Aug 2017
- First submitted
- 28 Jun 2013
- Last updated
- 21 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Eculizumab for Treatment of Antibody-mediated Rejection Following Renal Transplantation.
- ClinicalTrials.gov ID
- NCT01895127
- Acronym / sponsor ID
- 2013P001292
- Conditions
- Antibody-mediated Rejection, Humoral Rejection
- Keywords
- Kidney Transplant, Renal Transplant, Rejection, Antibody mediated, Humoral, Eculizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Study start
- Nov 2013
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 10 Jul 2013 (estimated)
- Results
- Posted 21 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label analysis that will compare eculizumab versus Plasmapheresis (PP) and Immunoglobulin (IVIg) for the treatment of antibody-mediated rejection (AMR) in renal transplant recipients. All patients will be evaluated from the time of AMR diagnosis for 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care | Active comparator | Biological: Immunoglobulin, Procedure: Plasmapheresis* Plasmapheresis (PP) x 3, at 40-60 cc/kg. * Immunoglobulin (IVIg), to be administered after each PP |
| Soliris (eculizumab) | Experimental | Drug: Eculizumab* 1200 mg first dose (Time: Screening/Week "0", after Biopsy Proven AMR) * 900 mg weekly for 4 doses (Weeks 1, 2, 3, 4) * 1200 mg week 5 * Week 6: If donor specific antibody < 50% of baseline DSA then no further treatment, otherwise 1200 mg weeks 7, 9 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adult renal transplant recipients, men and women between 18 and 75 years of age.
- Any patient with acute graft dysfunction (elevation of creatinine above post transplant nadir)
- Presence of circulating anti human leukocyte antigen (HLA) antibody (DSA "donor specific antibody").
- Histological findings compatible with Banff Class II or III AMR on transplant biopsy.
- Peritubular capillary c4d positivity on transplant biopsy.
Key exclusion criteria (18 listed)
- Patients that have received eculizumab prior to enrolling in the study.
- Patients with ongoing non-acute antibody mediated rejection.
- Patients with predominantly chronic antibody mediated rejection or interstitial fibrosis/tubular atrophy.
- History of severe cardiac disease (e.g., New York Heart Association [NYHA] Functional Class III or IV, myocardial infarction ≤ 6 months of randomization, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases)
- Prior splenectomy
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 |
|---|---|---|
| EculizumabAlso: Soliris | Drug | Soliris (eculizumab) |
| ImmunoglobulinAlso: IVIg | Biological | Standard of Care |
| Plasmapheresis | Procedure or surgery | Standard of Care |
Primary outcome
Percent Change in Estimated Glomerular Filtration (eGFR) Rate
Time frame: Month 3
Percent change in eGFR rate at 3 months post-treatment using the modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Anil K Chandraker, MD principal investigator
Brigham and Women's Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eculizumab, Immunoglobulin and Plasmapheresis in people with Antibody-mediated Rejection and Humoral Rejection, run by Brigham and Women's Hospital at 3 sites 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 6 inclusion and 18 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 21 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 21 Sep 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?
Percent Change in Estimated Glomerular Filtration (eGFR) Rate (time frame: Month 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Sep 2017.