Antibody Mediated RejectionPhase 2NCT01399593
Safety & Efficacy of Eculizumab to Prevent AMR in Living Donor Kidney Transplant Recipients Requiring Desensitization
A Phase 2 study testing Eculizumab in people with Antibody Mediated Rejection, run by Alexion Pharmaceuticals, Inc. at 41 sites in 10 countries.
Trial summary
The purpose of this trial was to determine the safety and efficacy of eculizumab in the prevention of antibody-mediated rejection (AMR) in sensitized recipients of a living donor kidney transplant requiring desensitization therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Antibody Mediated Rejection
- What is being tested?
- Eculizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 41 sitesin 10 countries
- Study dates
- 2 Nov 2011to 13 Nov 2015
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients ≥18 years old
- Patients with Stage IV or Stage V chronic kidney disease who will receive a kidney transplant from a living donor to whom they are sensitized and require desensitization prior to transplantation
Who cannot join
- ABO incompatible with living donor
- 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
Trial locations and contacts
41 sites in 10 countries.
41 sites in 10 countries
United States17 sites
Study site
Atlanta, Georgia, 30309
Study site
Baltimore, Maryland, 21205
Study site
Birmingham, Alabama, 35294
Study site
Boston, Massachusetts, 02115
Study site
Chapel Hill, North Carolina, 27599
Study site
Chicago, Illinois, 60612
Study site
Cincinnati, Ohio, 45267
Study site
Houston, Texas, 77030
Study site
La Jolla, California, 92037
Study site
Livingston, New Jersey, 07039
Study site
Los Angeles, California, 90095
Study site
New York, New York, 10032
Study site
Oklahoma City, Oklahoma, 73112
Study site
Rochester, Minnesota, 55905
Study site
San Francisco, California, 94143
Study site
St Louis, Missouri, 63110
Study site
Washington D.C., District of Columbia, 20007
United Kingdom6 sites
Study site
Birmingham, B15 2TH
Study site
Cambridge, CB2 2QQ
Study site
Coventry, CV2 2DX
Study site
London, England, SE1 9RT
Study site
London, England, W12 0HS
Study site
Oxford, England, OX3 7LJ
Australia4 sites
Study site
Camperdown, 2050
Study site
Clayton VIC, 3168
Study site
North Terrace, South Australia, 5000
Study site
Parkville VIC, 3050
France4 sites
Study site
Paris, 75010
Study site
Paris, 75743
Study site
Toulouse, 31059
Study site
Tours, 37044
Sweden3 sites
Study site
Gothenburg, 413 45
Study site
Huddinge, SE 141 86
Study site
Uppsala, S 751 85
About this study
Official title: A Randomized, Open-label, Multicenter Trial to Determine Safety and Efficacy of Eculizumab in the Prevention of Antibody Mediated Rejection (AMR) in Living Donor Kidney Transplant Recipients Requiring Desensitization Therapy
The purpose of this trial was to determine the safety and efficacy of eculizumab in the prevention of antibody-mediated rejection (AMR) in sensitized recipients of a living donor kidney transplant requiring desensitization therapy.
Read the detailed description
The main objective of this study was to evaluate the safety and efficacy of eculizumab to prevent AMR in sensitized recipients of living donor kidney transplants requiring desensitization therapy prior to transplantation. The primary endpoint focused on acute AMR during the first 9 weeks post-transplantation.
Patients were to be vaccinated against N. meningitidis at least 14 days prior to study drug initiation and revaccinated 30 days later. If not vaccinated 14 days prior, prophylactic antibiotics were to be administered. Pre-transplant infectious disease assessment was to be performed as part of the screening assessment.
Patients were to undergo desensitization therapy according to the practice of the local transplant center prior to transplantation, and this desensitization practice was to be uniformly applied for all patients at that center throughout the study. The actual length of desensitization for an individual patient was based on the clinical judgment of the Transplant Center team. Rituximab was prohibited in all patients as part of the pre-transplantation desensitization therapy due to potential pharmacodynamic interactions.
The control group was designed to test eculizumab against the best available care (referred to as standard of care, or SOC) consisting of plasmapheresis (PP) and/or intravenous immunoglobulin (IVIg). The best available care consisting of PP and IVIg was chosen because these modalities combined represented the most prevalent therapy reported in the literature and were the best available therapies at the time of this protocol's inception as per the transplant community.
- Conditions
- Antibody Mediated Rejection
- Being tested
- Eculizumab
- Keywords
- Antibody Mediated Rejection, AMR, Acute Humoral Rejection, AHR, Living Donor, Kidney Transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EculizumabDrug
Also called Soliris
| Study group | Role | What they receive |
|---|---|---|
| Eculizumab | Experimental | Patients were to receive eculizumab 1200 mg prior to allograft transplantation (Day 0, starting approximately one hour prior to kidney allograft reperfusion), eculizumab 900 mg (Days 1, 7, 14, 21, and 28), and eculizumab 1200 mg (Weeks 5, 7 and 9). All doses of eculizumab were administered intravenously: the median infusion time was 39 minutes. Receives: Drug: Eculizumab |
| Standard of Care | No intervention | Patients received standard of care (SOC) prophylactic therapy for acute AMR according to the SOC choice at each participating investigative site, which could have included any combination of plasmapheresis (PP) and intravenous immunoglobulin (IVIg). Patients randomized to SOC who were diagnosed with AMR could have received eculizumab for the treatment of AMR after initially receiving PP and/or IVIg. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Failure Rate
The primary efficacy variable was a binary outcome variable where patients meeting the composite endpoint of the occurrence of 1) biopsy-proven acute AMR, 2) graft loss, 3) patient death, or 4) loss to follow-up definition at Week 9 post-transplantation were considered treatment failures and all others were considered treatment successes.
Measured: 9 weeks post-transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2011 (estimated)
- Study start2 Nov 2011
- Primary completion13 May 2014
- Study completion13 Nov 2015
Why it stopped: Did not achieve statistical significance for primary endpoint
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Antibody Mediated RejectionStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The 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
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Masayo Ogawa, MD, Study director, Alexion Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01399593
- Sponsor's protocol ID
- C10-001
- Other IDs
- 2010-019630-28, BB-IND: 100,003
- Status last verified
- Sep 2017
- First submitted
- 19 Jul 2011
- Last updated
- 3 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Marks WH, Mamode N, Montgomery RA, Stegall MD, Ratner LE, Cornell LD, Rowshani AT, Colvin RB, Dain B, Boice JA, Glotz D; C10-001 Study Group. Safety and efficacy of eculizumab in the prevention of antibody-mediated rejection in living-donor kidney transplant recipients requiring desensitization therapy: A randomized trial. Am J Transplant. 2019 Oct;19(10):2876-2888. doi: 10.1111/ajt.15364. Epub 2019 Apr 19.
PubMed 30887675
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label, Multicenter Trial to Determine Safety and Efficacy of Eculizumab in the Prevention of Antibody Mediated Rejection (AMR) in Living Donor Kidney Transplant Recipients Requiring Desensitization Therapy
- ClinicalTrials.gov ID
- NCT01399593
- Acronym / sponsor ID
- C10-001
- Conditions
- Antibody Mediated Rejection
- Keywords
- Antibody Mediated Rejection, AMR, Acute Humoral Rejection, AHR, Living Donor, Kidney Transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Did not achieve statistical significance for primary endpoint
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 2 Nov 2011 (actual)
- Primary completion
- 13 May 2014 (actual)
- Study completion
- 13 Nov 2015 (actual)
- First posted
- 22 Jul 2011 (estimated)
- Results
- Posted 19 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial was to determine the safety and efficacy of eculizumab in the prevention of antibody-mediated rejection (AMR) in sensitized recipients of a living donor kidney transplant requiring desensitization therapy.
Detailed description
The main objective of this study was to evaluate the safety and efficacy of eculizumab to prevent AMR in sensitized recipients of living donor kidney transplants requiring desensitization therapy prior to transplantation. The primary endpoint focused on acute AMR during the first 9 weeks post-transplantation.
Patients were to be vaccinated against N. meningitidis at least 14 days prior to study drug initiation and revaccinated 30 days later. If not vaccinated 14 days prior, prophylactic antibiotics were to be administered. Pre-transplant infectious disease assessment was to be performed as part of the screening assessment.
Patients were to undergo desensitization therapy according to the practice of the local transplant center prior to transplantation, and this desensitization practice was to be uniformly applied for all patients at that center throughout the study. The actual length of desensitization for an individual patient was based on the clinical judgment of the Transplant Center team. Rituximab was prohibited in all patients as part of the pre-transplantation desensitization therapy due to potential pharmacodynamic interactions.
The control group was designed to test eculizumab against the best available care (referred to as standard of care, or SOC) consisting of plasmapheresis (PP) and/or intravenous immunoglobulin (IVIg). The best available care consisting of PP and IVIg was chosen because these modalities combined represented the most prevalent therapy reported in the literature and were the best available therapies at the time of this protocol's inception as per the transplant community.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Eculizumab | Experimental | Drug: EculizumabPatients were to receive eculizumab 1200 mg prior to allograft transplantation (Day 0, starting approximately one hour prior to kidney allograft reperfusion), eculizumab 900 mg (Days 1, 7, 14, 21, and 28), and eculizumab 1200 mg (Weeks 5, 7 and 9). All doses of eculizumab were administered intravenously: the median infusion time was 39 minutes. |
| Standard of Care | No intervention | –Patients received standard of care (SOC) prophylactic therapy for acute AMR according to the SOC choice at each participating investigative site, which could have included any combination of plasmapheresis (PP) and intravenous immunoglobulin (IVIg). Patients randomized to SOC who were diagnosed with AMR could have received eculizumab for the treatment of AMR after initially receiving PP and/or IVIg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Male or female patients ≥18 years old
- Patients with Stage IV or Stage V chronic kidney disease who will receive a kidney transplant from a living donor to whom they are sensitized and require desensitization prior to transplantation
Key exclusion criteria (2 listed)
- ABO incompatible with living donor
- 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
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 | Eculizumab |
Primary outcome
Treatment Failure Rate
Time frame: 9 weeks post-transplantation
The primary efficacy variable was a binary outcome variable where patients meeting the composite endpoint of the occurrence of 1) biopsy-proven acute AMR, 2) graft loss, 3) patient death, or 4) loss to follow-up definition at Week 9 post-transplantation were considered treatment failures and all others were considered treatment successes.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30887675Marks WH, Mamode N, Montgomery RA, Stegall MD, Ratner LE, Cornell LD, Rowshani AT, Colvin RB, Dain B, Boice JA, Glotz D; C10-001 Study Group. Safety and efficacy of eculizumab in the prevention of antibody-mediated rejection in living-donor kidney transplant recipients requiring desensitization therapy: A randomized trial. Am J Transplant. 2019 Oct;19(10):2876-2888. doi: 10.1111/ajt.15364. Epub 2019 Apr 19.
- Individual participant dataSharing planned: No
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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.
Masayo Ogawa, MD study director
Alexion Pharmaceuticals, Inc.
41 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eculizumab in people with Antibody Mediated Rejection, run by Alexion Pharmaceuticals, Inc. at 41 sites in 10 countries.
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 2 inclusion and 2 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 3 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in United States, United Kingdom, Australia, France, Sweden and 5 more countries. 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 19 Apr 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?
Treatment Failure Rate (time frame: 9 weeks post-transplantation). 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 NCT01399593, which also lists 1 linked publication.
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 3 Oct 2017.