Acute Antibody-Mediated Rejection (AMR)Phase 3NCT02547220
A Multicenter Study to Evaluate the Efficacy and Safety of Cinryze® for the Treatment of Acute Antibody-mediated Rejection in Participants With Kidney Transplant
A Phase 3 study testing Cinryze® in people with Acute Antibody-Mediated Rejection (AMR), run by Shire at 47 sites in 6 countries.
Trial summary
The main purpose of the study is to evaluate the efficacy of CINRYZE administered with plasmapheresis, plasma exchange, or immune adsorption treatments and sucrose-free immunoglobulin (IVIg) for the treatment of acute antibody-mediated rejection (AMR) of renal allograft in kidney transplant recipients as measured by… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Antibody-Mediated Rejection (AMR)
- What is being tested?
- Cinryze®
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 47 sitesin 6 countries
- Study dates
- 20 May 2016to 31 May 2019
- Phase
- Phase 3
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be greater than or equal to (>=) 18 and less than or equal to (<=) 70 years of age.
- Weigh >= 45 kg with a body mass index (BMI) less than (<) 35 kilogram (kg)/meter (m)^2 at screening.
- Have human leukocyte antigen (HLA) donor-specific antibody (DSA) identified at the time of diagnosis of AMR. If it is anticipated that the local DSA results will not be available within the screening period, previously obtained local DSA results can be used to assess eligibility, if obtained after kidney transplant and within 30 days prior to the qualifying AMR episode. In any instance, a local DSA test should still be performed at the time of AMR diagnosis.
- Have a first qualifying episode of AMR in the participant's current renal allograft between 72 hours (h) and 12 months after transplant defined by a renal allograft biopsy demonstrating neutrophil and/or monocyte infiltration in the peritubular capillaries (PTC) and/or glomeruli with or without evidence of 4th complement protein degradation product (C4d) deposition by immunohistopathology according to 2013 Banff criteria.
- Have achieved adequate renal function defined as: Pre-AMR baseline estimated glomerular filtration rate calculated by the Modification of Diet in Renal Disease (eGFRMDRD) >=20 millilitre (mL)/minute (min) /1.73m^2 for a qualifying AMR episode occurring <=21 days after transplant or pre-AMR baseline eGFRMDRD >=30 mL/min/1.7m^2 for a qualifying AMR episode occurring greater than (>) 21 days after transplant. The pre-AMR baseline is the highest eGFRMDRD value obtained following the kidney transplant and within 30 days prior to the qualifying AMR episode. If more than 1 eGFRMDRD value is available, a mean of the 2 highest values (at least 1 day apart and both prior to the AMR episode) will be used as the pre-AMR baseline value. If no eGFRMDRD was obtained within 30 days prior to biopsy, it can be evaluated within a 60 day period.
- Receive first dose of investigational product after 7 days after the kidney transplant procedure and within 7 days after the qualifying renal allograft biopsy procedure that was positive for AMR.
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- Be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
- If female and of child-bearing potential, must have a negative urine pregnancy test confirmed by a negative serum beta human chorionic gonadotropin (beta-HCG) pregnancy test at the Screening Visit and must have a negative urine pregnancy test at the Day 1 visit.
- Agree to comply with any applicable contraceptive requirements of the protocol.
Who cannot join
- Have received pediatric en bloc kidney transplant.
- Have primary Focal Segmental Glomerulosclerosis, rapidly progressive glomerulonephritis, membrano-proliferative glomerulonephritis type 1 (including C3 glomerulopathy), "dense deposit disease", or thrombotic microangiopathy as the cause of native kidney failure.
- Have prior or concurrent non-renal solid organ transplant or hematopoietic stem cell transplant (HSCT) or have more than 2 completed kidney transplant procedures (note: 1 double kidney transplant procedure is considered to be 1 procedure).
- Have a known neoplastic lesion in the transplanted allograft
- Have, any ongoing infection that causes hemodynamic compromise or as determined by the investigator, any surgical or medical condition that could interfere with the administration of investigational product, interpretation of study results, or could compromise participant safety, including (as determined by the transplanting surgeon and documented in the operative report) any major technical complications of the renal artery, renal vein, or ureteral anastomosis
- Have ongoing treatment for hepatitis C virus (HCV) infection.
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- Have had a recent myocardial infarction (MI) within the past 6 months and/or at the time of screening are treated with anticoagulants and/or antiplatelet agents (excluding aspirin) for a previous myocardial infarction.
- Have a history of: abnormal bleeding, clotting events or disorders (excluding a history of clotted hemodialysis access or superficial thrombophlebitis in the absence of medically confirmed coagulopathy), any coagulopathy (documented or clinically suspected) For example, participants should be excluded if they have a history of renal allograft arterial or venous thrombosis, deep vein thrombosis, pulmonary embolism, ischemic cerebrovascular accident (stroke) or transient ischemic attack (TIA), any large vessel thrombosis.
- Have a history of allergic reaction to CINRYZE or other blood products.
- Have had any change in androgen therapy (example, danazol, oxandrolone, stanozolol, testosterone), tranexamic acid, epsilon-aminocaproic acid, or other fibrinolytics within 3 months before the first dose of investigational product.
- Have participated in the active dosing phase of any other investigational drug study within 30 days prior to dosing with investigational product.
- Have any of the following local laboratory values reported prior to dosing with investigational product: Within 24 h prior to participant dosing, white blood cell (WBC) count <0.5×109/litre (L) or >20×109/L (the value of >20×109/L should be excluded if obtained during steroid treatment), Within 24 h prior to participant dosing platelet count <25×109/L or >600×109/L
- Be pregnant or breastfeeding.
- Have received any of the following agents within 1 month prior to the first dose of investigational product: Sucrose-containing intravenous immunoglobulin (IVIg), Any C1 inhibitor (C1 INH) (plasma-derived [example, CINRYZE®, Berinert®, Cetor®] or recombinant [example, Rhucin®]), Eculizumab (Soliris®), Ecallantide (Kalbitor®).
Trial locations and contacts
47 sites in 6 countries.
47 sites in 6 countries
United States29 sites
Piedmont Hospital
Atlanta, Georgia, 30309
University Of Colorado School Of Medicine
Aurora, Colorado, 80045
University of Maryland Medical Center
Baltimore, Maryland, 21201
Johns Hopkins University
Baltimore, Maryland, 21287
Brigham and Womens Hospital
Boston, Massachusetts, 02115
Northwestern Memorial Hospital
Chicago, Illinois, 60611
University of Cincinnati
Cincinnati, Ohio, 45220
Cleveland Clinic
Cleveland, Ohio, 44195
Ohio State University Medical Center
Columbus, Ohio, 43210
Baylor All Saints Medical Center
Fort Worth, Texas, 76104
Houston Methodist Hospital
Houston, Texas, 77030
Saint Barnabas Medical Center
Livingston, New Jersey, 07039
Kidney Transplant Research Office at UCLA
Los Angeles, California, 90024
Keck School of Medicine at USC
Los Angeles, California, 90033
Jackson Memorial Hospital
Miami, Florida, 33136
University of Minnesota
Minneapolis, Minnesota, 55414
University of Pittsburgh Medical Center
Monroeville, Pennsylvania, 15146
Vanderbilt University Medical Center
Nashville, Tennessee, 37204
Mount Sinai Hospital
New York, New York, 10029
Columbia University Medical Center
New York, New York, 10032
New York Presbyterian Hospital - Weill-Cornell
New York, New York, 10065
INTEGRIS Nazih Zuhdi Transplant Institute
Oklahoma City, Oklahoma, 73112
Florida Hospital Transplant Institute
Orlando, Florida, 32804
University of Pennsylvania Health System
Philadelphia, Pennsylvania, 19104
University of Utah Health Sciences Center
Salt Lake City, Utah, 84132
University of California San Francisco
San Francisco, California, 94110
Washington University School of Medicine
St Louis, Missouri, 63110
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20057
NYU Longone Medical Center
White Plains, New York, 10605
France7 sites
Hopital Henri Mondor
Créteil, Val-De-Marne, 94010
CHU Michallon
Grenoble, 38043
Centre Hospitalier Universitaire de Bicêtre
Le Kremlin-Bicêtre, 94275
Hotel Dieu
Nantes, Loire-Atlantique, 44093
Hôpital Saint Louis
Paris, 75010
Groupe Hospitalier Necker Enfants Malades
Paris, 75015
Hôpital de Rangueil
Toulouse, 31059
Spain4 sites
Hospital Universitario Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Universitari de Bellvitge
Barcelona, 8907
Hospital Clinico San Carlos
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Germany3 sites
Universitätsklinikum Hamburg Eppendorf
Hamburg, 20246
Universität Heidelberg
Heidelberg, Baden-Wurttemberg, 69120
Universitätsklinikum Frankfurt
Steinbach, Hesse, 61449
Canada2 sites
Royal Victoria Hospital
Montreal, Quebec, H4A 3J1
Providence Health Care Research Institute
Vancouver, British Columbia, V6Z 2K5
Netherlands2 sites
Universitair Medisch Centrum Groningen
Groningen, 9713 GZ
Erasmus MC
Rotterdam, 3015 CE
About this study
Official title: A Randomized Double-blind Placebo-controlled Study to Evaluate the Efficacy and Safety of Cinryze® (C1 Esterase Inhibitor [Human]) for the Treatment of Acute Antibody-mediated Rejection in Kidney Transplant Patients
The main purpose of the study is to evaluate the efficacy of CINRYZE administered with plasmapheresis, plasma exchange, or immune adsorption treatments and sucrose-free immunoglobulin (IVIg) for the treatment of acute antibody-mediated rejection (AMR) of renal allograft in kidney transplant recipients as measured by the proportion of participants with new or worsening transplant glomerulopathy (TG) at 6 months after treatment initiation.
- Conditions
- Acute Antibody-Mediated Rejection (AMR)
- Being tested
- Cinryze®, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cinryze®Biological
Participants will receive 5000 Units of CINRYZE (50 millilitre [mL] of CINRYZE/ 50 mL of normal saline) on Day 1 and 2500 Units of CINRYZE (25 mL of CINRYZE/ 75 mL of normal saline) on Day 3, 5, 7, 9, 11, and 13 respectively.
PlaceboDrug
Participants will receive 7 doses of matched placebo over 13 days of treatment.
| Study group | Role | What they receive |
|---|---|---|
| Cinryze® | Experimental | Participants will receive 5000 Units of CINRYZE (50 millilitre [mL] of CINRYZE/ 50 mL of normal saline) on Day 1 and 2500 Units of CINRYZE (25 mL of CINRYZE/ 75 mL of normal saline) on Day 3, 5, 7, 9, 11, and 13 respectively. Receives: Biological: Cinryze® |
| Placebo | Placebo comparator | Participants will receive 7 doses of matched placebo over 13 days of treatment. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With New or Worsening Transplant Glomerulopathy (TG) at Month 6 Post-Treatment
New or worsening TG at month 6 by the standard score was defined as an increase in one or more between qualifying biopsy and 6-month biopsy. New or worsening TG was measured by Banff 2013 criteria (standard score) using allograft glomerulopathy (Cg0-Cg3): Cg0- No GBM double contours by light microscopy (LM) or electron microscopy (EM); Cg1- no GBM double contours by LM but GBM double contours in at least 3 glomerular capillaries by EM; Cg2- Double contours affecting 26 to 50% of peripheral capillary loops in the most affected of nonsclerotic glomeruli; Cg3- Double contours affecting more than 50% of peripheral capillary loops in the most affected of nonsclerotic glomeruli with a score range of 0 (no allograft glomerulopathy) and 3 (severe glomerulopathy). Percentage of participants with new or worsening TG at Month 6 post-treatment was reported.
Measured: Month 6
Secondary outcomes (14)
Number of Participants With All-Cause Graft Failure at Month 48
Graft failure was determined as the presence of one or more of the following criteria: institution of permanent dialysis (defined as dialysis treatment more than [>] 30 days), current transplant nephrectomy, and/or a clinical determination of cessation of kidney graft function and estimated glomerular filtration rate (eGFR) less than or equal to (<=) 15 milliliter (mL)/minute (min)/1.73 meter (m)^2.
Measured: Month 48
Change From Baseline in Renal Function up to Month 48
Renal function was measured as glomerular filtration rate calculated by the modification of diet in renal disease (eGFRMDRD).
Measured: Baseline, up to Month 48
Change From Baseline With Pre-Antibody-Mediated Rejection (AMR) in Renal Function up to Month 48
Renal function was measured as glomerular filtration rate calculated by the modification of diet in renal disease (eGFRMDRD). Pre-AMR baseline was the highest eGFRMDRD value obtained following the kidney transplant and within 30 days prior to the qualifying AMR episode.
Measured: Pre-AMR Baseline, up to Month 48
Number of Participants With Proteinuria Levels at Month 48
Proteinuria included spot urine protein, urine creatinine, and urine protein/urine creatinine ratio.
Measured: Month 48
Change From Pre-Antibody-Mediated Rejection (AMR) Baseline in Histopathology Per Banff Criteria at Month 6
Histopathological diagnosis of acute rejection was measured by Banff 2013 criteria: Glomerulitis score (g0-g3), allograft glomerulopathy (Cg0-cg3), Tubulitis score (T0-T3), Intimal arteritis score (V0-V3), peritubular capillaritis (PTC) (ptc0-ptc3) and Interstitial Inflammation score (i0-i3). The histopathology was a composite of the sub-scores. Each of the sub-scores or histopathology score ranges from 0 ( no histopathology) to 3 (more severe histopathology).
Measured: Pre-AMR Baseline, Month 6
Number of Participants With All-Cause Graft Failure at Month 6
Graft failure was determined by the presence of one or more of the following criteria: institution of permanent dialysis (defined as dialysis treatment more than [>] 30 days), current transplant nephrectomy, and/or a clinical determination of cessation of kidney graft function and estimated glomerular filtration rate (eGFR) less than or equal to (<=) 15 milliliter (mL)/minute (min)/1.73 meter (m)^2.
Measured: Month 6
Number of Participants With Graft Failure Due to Antibody-Mediated Rejection (AMR) Episodes at Month 48
Graft failure was determined by the presence of one or more of the following criteria: institution of permanent dialysis (defined as dialysis treatment more than [>] 30 days), current transplant nephrectomy, and/or a clinical determination of cessation of kidney graft function and estimated glomerular filtration rate (eGFR) less than or equal to (<=) 15 milliliter (mL)/minute (min)/1.73 meter (m)^2.
Measured: Month 48
Time to All-Cause Graft Failure up to Month 48
Graft failure was determined by the presence of one or more of the following criteria: institution of permanent dialysis (defined as dialysis treatment more than [>] 30 days), current transplant nephrectomy, and/or a clinical determination of cessation of kidney graft function and estimated glomerular filtration rate (eGFR) less than or equal to (<=) 15 milliliter (mL)/minute (min)/1.73 meter (m)^2. Time to all-cause graft failure in months was calculated as (Date of graft failure - Date of first dose + 1)/30.25.
Measured: Up to Month 48
Time to Graft Failure Due to Antibody-Mediated Rejection (AMR) Episodes up to Month 48
Graft failure was determined by the presence of one or more of the following criteria: institution of permanent dialysis (defined as dialysis treatment > 30 days), current transplant nephrectomy, and/or a clinical determination of cessation of kidney graft function and eGFR <=15 mL/ min/1.73m^2. Time to graft failure due to AMR episodes in months was calculated as (Date of graft failure due to AMR - Date of first dose + 1)/30.25.
Measured: Up to Month 48
Number of Participants With Resolution of the Qualifying Antibody-Mediated Rejection (AMR) Episodes at Month 48
Number of participants with resolution of the qualifying AMR episodes at Month 48.
Measured: Month 48
Time to Resolution of Qualifying Antibody-Mediated Rejection (AMR) Episodes up to Month 48
Time to resolution of qualifying AMR episodes was calculated as (Date of qualifying AMR resolution - Date of first dose + 1)/30.25. Participants who didn't had resolution of qualifying AMR episodes and still on-study were censored at the date of last visit; Participants who had completed the study without resolution of qualifying AMR were censored at the date of study completion; participants who discontinued from the study without resolution of qualifying AMR were censored at the date of early discontinuation.
Measured: Up to Month 48
Number of Participants Who Were Alive at Month 36
Number of participants who were alive at Month 36 (study terminated instead of Month 48) were reported.
Measured: Month 36
Time to All-Cause Mortality up to Month 48
Time to all-cause mortality was calculated as (Date of discontinuation due to death - Date of first dose + 1)/30.25. Participants who are alive and still on-study were censored at the date of last visit; Participants who had completed the study were censored at the date of study completion; Participants who discontinued from the study but not due to death were censored at the date of early discontinuation.
Measured: Up to Month 48
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward, undesired, unplanned clinical event in the form of signs, symptoms, disease, or laboratory or physiological observations occurred in a participant participating in a clinical study with the sponsor's product, regardless of causal relationship. TEAEs were defined as events that started or worsened on or after the date of the first dose of investigational product, but no later than 30 days following the last dose of investigational product, within a treatment period.
Measured: From start of study drug administration up to study termination (Month 36)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2015 (estimated)
- Study start20 May 2016
- Primary completion31 May 2019
- Study completion31 May 2019
Why it stopped: Following a pre-scheduled interim analysis performed by the DMC, it was determined that the study met the pre-specified criteria for futility.
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 Acute Antibody-Mediated Rejection (AMR)Studies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Shire
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02547220
- Sponsor's protocol ID
- SHP616-302
- Other IDs
- 2015-000726-11, 2015
- Status last verified
- May 2020
- First submitted
- 2 Sep 2015
- Last updated
- 13 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
Publications
Karpman D, Bekassy Z, Grunenwald A, Roumenina LT. A role for complement blockade in kidney transplantation. Cell Mol Immunol. 2022 Jul;19(7):755-757. doi: 10.1038/s41423-022-00854-5. Epub 2022 Mar 24. No abstract available.
PubMed 35332298
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-blind Placebo-controlled Study to Evaluate the Efficacy and Safety of Cinryze® (C1 Esterase Inhibitor [Human]) for the Treatment of Acute Antibody-mediated Rejection in Kidney Transplant Patients
- ClinicalTrials.gov ID
- NCT02547220
- Acronym / sponsor ID
- SHP616-302
- Conditions
- Acute Antibody-Mediated Rejection (AMR)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Following a pre-scheduled interim analysis performed by the DMC, it was determined that the study met the pre-specified criteria for futility.
- Enrolment
- 39 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 20 May 2016 (actual)
- Primary completion
- 31 May 2019 (actual)
- Study completion
- 31 May 2019 (actual)
- First posted
- 11 Sep 2015 (estimated)
- Results
- Posted 13 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of the study is to evaluate the efficacy of CINRYZE administered with plasmapheresis, plasma exchange, or immune adsorption treatments and sucrose-free immunoglobulin (IVIg) for the treatment of acute antibody-mediated rejection (AMR) of renal allograft in kidney transplant recipients as measured by the proportion of participants with new or worsening transplant glomerulopathy (TG) at 6 months after treatment initiation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cinryze® | Experimental | Biological: Cinryze®Participants will receive 5000 Units of CINRYZE (50 millilitre [mL] of CINRYZE/ 50 mL of normal saline) on Day 1 and 2500 Units of CINRYZE (25 mL of CINRYZE/ 75 mL of normal saline) on Day 3, 5, 7, 9, 11, and 13 respectively. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive 7 doses of matched placebo over 13 days of treatment. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Be greater than or equal to (>=) 18 and less than or equal to (<=) 70 years of age.
- Weigh >= 45 kg with a body mass index (BMI) less than (<) 35 kilogram (kg)/meter (m)^2 at screening.
- Have human leukocyte antigen (HLA) donor-specific antibody (DSA) identified at the time of diagnosis of AMR. If it is anticipated that the local DSA results will not be available within the screening period, previously obtained local DSA results can be used to assess eligibility, if obtained after kidney transplant and within 30 days prior to the qualifying AMR episode. In any instance, a local DSA test should still be performed at the time of AMR diagnosis.
- Have a first qualifying episode of AMR in the participant's current renal allograft between 72 hours (h) and 12 months after transplant defined by a renal allograft biopsy demonstrating neutrophil and/or monocyte infiltration in the peritubular capillaries (PTC) and/or glomeruli with or without evidence of 4th complement protein degradation product (C4d) deposition by immunohistopathology according to 2013 Banff criteria.
- Have achieved adequate renal function defined as: Pre-AMR baseline estimated glomerular filtration rate calculated by the Modification of Diet in Renal Disease (eGFRMDRD) >=20 millilitre (mL)/minute (min) /1.73m^2 for a qualifying AMR episode occurring <=21 days after transplant or pre-AMR baseline eGFRMDRD >=30 mL/min/1.7m^2 for a qualifying AMR episode occurring greater than (>) 21 days after transplant. The pre-AMR baseline is the highest eGFRMDRD value obtained following the kidney transplant and within 30 days prior to the qualifying AMR episode. If more than 1 eGFRMDRD value is available, a mean of the 2 highest values (at least 1 day apart and both prior to the AMR episode) will be used as the pre-AMR baseline value. If no eGFRMDRD was obtained within 30 days prior to biopsy, it can be evaluated within a 60 day period.
Key exclusion criteria (14 listed)
- Have received pediatric en bloc kidney transplant.
- Have primary Focal Segmental Glomerulosclerosis, rapidly progressive glomerulonephritis, membrano-proliferative glomerulonephritis type 1 (including C3 glomerulopathy), "dense deposit disease", or thrombotic microangiopathy as the cause of native kidney failure.
- Have prior or concurrent non-renal solid organ transplant or hematopoietic stem cell transplant (HSCT) or have more than 2 completed kidney transplant procedures (note: 1 double kidney transplant procedure is considered to be 1 procedure).
- Have a known neoplastic lesion in the transplanted allograft
- Have, any ongoing infection that causes hemodynamic compromise or as determined by the investigator, any surgical or medical condition that could interfere with the administration of investigational product, interpretation of study results, or could compromise participant safety, including (as determined by the transplanting surgeon and documented in the operative report) any major technical complications of the renal artery, renal vein, or ureteral anastomosis
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 |
|---|---|---|
| Cinryze®Participants will receive 5000 Units of CINRYZE (50 millilitre [mL] of CINRYZE/ 50 mL of normal saline) on Day 1 and 2500 Units of CINRYZE (25 mL of CINRYZE/ 75 mL of normal saline) on Day 3, 5, 7, 9, 11, and 13 respectively. | Biological | Cinryze® |
| PlaceboParticipants will receive 7 doses of matched placebo over 13 days of treatment. | Drug | Placebo |
Primary outcome
Percentage of Participants With New or Worsening Transplant Glomerulopathy (TG) at Month 6 Post-Treatment
Time frame: Month 6
New or worsening TG at month 6 by the standard score was defined as an increase in one or more between qualifying biopsy and 6-month biopsy. New or worsening TG was measured by Banff 2013 criteria (standard score) using allograft glomerulopathy (Cg0-Cg3): Cg0- No GBM double contours by light microscopy (LM) or electron microscopy (EM); Cg1- no GBM double contours by LM but GBM double contours in at least 3 glomerular capillaries by EM; Cg2- Double contours affecting 26 to 50% of peripheral capillary loops in the most affected of nonsclerotic glomeruli; Cg3- Double contours affecting more than 50% of peripheral capillary loops in the most affected of nonsclerotic glomeruli with a score range of 0 (no allograft glomerulopathy) and 3 (severe glomerulopathy). Percentage of participants with new or worsening TG at Month 6 post-treatment was reported.
14 secondary outcomes
Number of Participants With All-Cause Graft Failure at Month 48
Time frame: Month 48
Change From Baseline in Renal Function up to Month 48
Time frame: Baseline, up to Month 48
Change From Baseline With Pre-Antibody-Mediated Rejection (AMR) in Renal Function up to Month 48
Time frame: Pre-AMR Baseline, up to Month 48
Number of Participants With Proteinuria Levels at Month 48
Time frame: Month 48
Change From Pre-Antibody-Mediated Rejection (AMR) Baseline in Histopathology Per Banff Criteria at Month 6
Time frame: Pre-AMR Baseline, Month 6
Number of Participants With All-Cause Graft Failure at Month 6
Time frame: Month 6
Number of Participants With Graft Failure Due to Antibody-Mediated Rejection (AMR) Episodes at Month 48
Time frame: Month 48
Time to All-Cause Graft Failure up to Month 48
Time frame: Up to Month 48
Time to Graft Failure Due to Antibody-Mediated Rejection (AMR) Episodes up to Month 48
Time frame: Up to Month 48
Number of Participants With Resolution of the Qualifying Antibody-Mediated Rejection (AMR) Episodes at Month 48
Time frame: Month 48
Time to Resolution of Qualifying Antibody-Mediated Rejection (AMR) Episodes up to Month 48
Time frame: Up to Month 48
Number of Participants Who Were Alive at Month 36
Time frame: Month 36
Time to All-Cause Mortality up to Month 48
Time frame: Up to Month 48
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From start of study drug administration up to study termination (Month 36)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35332298Karpman D, Bekassy Z, Grunenwald A, Roumenina LT. A role for complement blockade in kidney transplantation. Cell Mol Immunol. 2022 Jul;19(7):755-757. doi: 10.1038/s41423-022-00854-5. Epub 2022 Mar 24. No abstract available.
- Individual participant dataSharing planned: Yes. Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
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.
Study Director study director
Shire
47 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cinryze® in people with Acute Antibody-Mediated Rejection (AMR), run by Shire at 47 sites in 6 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 9 inclusion and 14 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 13 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 47 sites in United States, France, Spain, Germany, Canada and 1 more country. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 13 Jul 2020). 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?
Percentage of Participants With New or Worsening Transplant Glomerulopathy (TG) at Month 6 Post-Treatment (time frame: Month 6). 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 NCT02547220, 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 13 Jul 2020.