Antibody-mediated RejectionPhase 3NCT03221842
Efficacy and Safety of Human Plasma-derived C1-esterase Inhibitor as add-on to Standard of Care for the Treatment of Refractory Antibody Mediated Rejection (AMR) in Adult Renal Transplant Recipients
A Phase 3 study testing C1-esterase inhibitor in people with Antibody-mediated Rejection, run by CSL Behring at 26 sites in 7 countries.
Trial summary
This is a double-blind, randomized-withdrawal, placebo-controlled study in kidney transplant patients with AMR to evaluate the efficacy and safety of human plasma-derived C1-esterase inhibitor as add-on to standard of care (IVIG). 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?
- C1-esterase inhibitor
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 26 sitesin 7 countries
- Study dates
- 6 Nov 2017to 20 Jan 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female at least 18 years of age;
- Evidence of at least one donor-specific antibody (DSA);
- Recipient of a kidney transplant;
- Achieved a steady-state, post-transplant eGFR ≥ 40 mL/min/1.73 m2 within 60 days of post-transplant OR a 50% increase in urine output with a 50% decrease in serum creatinine over the first 7 days post-transplant in subjects with slow or delayed graft function;
- Acute AMR.
Who cannot join
- Recipient of an en bloc kidney transplant;
- Current active hepatitis C virus (HCV) infection;
- Active bacterial or fungal infection;
- Ongoing dialysis >2 weeks;
- Known congenital bleeding or coagulopathy disorder;
- Current cancer or a history of cancer;
- Female subjects who are pregnant or breast feeding;
- Male or female subjects who are unwilling to use contraception or who are not surgically sterile.
Trial locations and contacts
26 sites in 7 countries.
26 sites in 7 countries
United States13 sites
University of Alabama Hospital (at Birmingham)
Birmingham, Alabama, 35233
Brigham & Women's
Boston, Massachusetts, 02115
University of Illinois Chicago
Chicago, Illinois, 60612
Houston Methodist
Houston, Texas, 77030
St. Barnabas Medical Center
Livingston, New Jersey, 07039
University of Wisconsin
Madison, Wisconsin, 53705-2281
Vanderbilt University
Nashville, Tennessee, 37232
Yale New Haven Hospital
New Haven, Connecticut, 06520
NYU
New York, New York, 10016
Columbia University
New York, New York, 10032
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Mayo Clinic (Rochester)
Rochester, Minnesota, 55905
California Pacific
San Francisco, California, 94115
France7 sites
CHU de Bordeaux. Hôpital Pellegrin
Bordeaux, 33000
CHU de Grenoble - Hôpital Michalon
Grenoble, 38043
Centre Regional Hospitalier Universitaire de Lille
Lille, 59000
Hospital Edouard Herriot Lyon
Lyon, 69003
Hopital saint Louis Paris
Paris, 75010
Necker Hospital
Paris, 75743
CHU Rangueil
Toulouse, 31059
Spain2 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Clinic de Barcelona
Barcelona, 08036
About this study
Official title: A Double-blind, Randomized-withdrawal, Placebo-controlled Study to Evaluate the Efficacy and Safety of Human Plasma-derived C1-esterase Inhibitor as add-on to Standard of Care for the Treatment of Refractory Antibody Mediated Rejection in Adult Renal Transplant Recipients
This is a double-blind, randomized-withdrawal, placebo-controlled study in kidney transplant patients with AMR to evaluate the efficacy and safety of human plasma-derived C1-esterase inhibitor as add-on to standard of care (IVIG).
- Conditions
- Antibody-mediated Rejection
- Being tested
- C1-esterase inhibitor, Placebo
- Keywords
- Antibody-mediated kidney transplant rejection, Renal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C1-esterase inhibitorDrug
Also called C1-INH
C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution
PlaceboDrug
Excipients of C1-INH plus albumin
| Study group | Role | What they receive |
|---|---|---|
| C1-INH | Experimental | C1-esterase inhibitor Receives: Drug: C1-esterase inhibitor |
| Placebo | Placebo comparator | Excipients of C1-INH plus albumin Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of Participants With Loss-of-response During Treatment Period 2 (TP2)
Loss of response is defined as 1 of the following, whichever occurs first:
- Decline in Estimated Glomerular Filtration Rate (eGFR), or
- Allograft failure, or
- Subject death by any cause.
Measured: Up to 38 weeks
Secondary outcomes (13)
Number of Participants With All-cause Allograft Failure During TP2
Allograft failure is defined as 1 of the following:
- Allograft nephrectomy, institution of permanent dialysis, or return to the transplant waitlist for renal transplant, whichever occurs first, OR
- Subject death by any cause
Measured: Up to 38 weeks
Percent of Participants With All-cause Allograft Failure During TP2
Measured: Up to 38 weeks
Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of Treatment Period 1 (TP1)
Measured: Baseline and 13 weeks
Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of TP2
Measured: Baseline and 38 weeks
The Rate of Change of eGFR During TP2 as Defined by the Slope of the Mean Regression of eGFR Over Time at End of TP2
The Sponsor terminated the study due to futility of enrolment. Because of the study termination, limited efficacy results are presented in this report.
Measured: Up to 38 weeks
Time to All-cause Allograft Failure Through the Follow up Period
The Sponsor terminated the study due to futility of enrolment. Because of the study termination, limited efficacy results are presented in this report.
Measured: Up to approximately 208 weeks
Number of Responders at the End-of-TP1
Responders were defined as subjects whose End-of-TP1 eGFR was ≥ 90% of baseline eGFR and ≥ 20 mL/min/1.73 m2.
Measured: Up to 13 weeks
Percent of Responders at the End-of-TP1
Responders were defined as subjects whose End-of-TP1 eGFR was ≥ 90% of baseline eGFR and ≥ 20 mL/min/1.73 m2.
Measured: Up to 13 weeks
Proportion of Subjects Surviving Through the Follow-up Period
The Sponsor terminated the study due to futility of enrolment. Because of the study termination, limited efficacy results are presented in this report.
Measured: Up to approximately 208 weeks
Percent of Participants With Any Adverse Event (AE) Assessed as Related to Investigational Product
Measured: Up to approximately 42 weeks after the time of first investigational product administration
Mean Pre-dose C1-esterase Inhibitor Functional Activity
C1-esterase Inhibitor may play a role in the prevention of antibody-mediated rejection (AMR) following kidney transplant. Low levels of C1 esterase inhibitor concentration and its functional activity may lead to AMR. Patients with AMR may go on to lose their kidney transplant and have other associated health risks. Levels of C1-esterase inhibitor functional activity in plasma is described as a percent.
Measured: Up to 13 weeks
Area Under the Plasma Concentration Time Curve (AUC0-t) for C1-INH Functional Activity
C1-esterase Inhibitor may play a role in the prevention of antibody-mediated rejection (AMR) following kidney transplant. Low levels of C1 esterase inhibitor concentration and its functional activity may lead to AMR. Patients with AMR may go on to lose their kidney transplant and have other associated health risks. Levels of C1-esterase inhibitor functional activity is described as a percent.
Measured: Up to 72 hours after post-dose on Day 10 and on Day 77 of Period 1
Time to Maximum Plasma Concentration (Tmax) for C1-INH Functional Activity
Measured: Up to 72 hours after post-dose on Day 10 and on Day 77 of Period 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2017
- Study start6 Nov 2017
- Primary completion20 Jan 2021
- Study completion20 Jan 2021
Why it stopped: The study was terminated early due to futility of enrolment and not for safety reasons.
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 CSL BehringThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Randomized-withdrawal
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Program Director, Study director, CSL Behring
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03221842
- Sponsor's protocol ID
- CSL842_3001
- Other IDs
- 2017-000348-17, 2017
- Status last verified
- Jul 2022
- First submitted
- 17 Jul 2017
- Last updated
- 29 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Viklicky O, Slatinska J, Novotny M, Hruba P. Developments in immunosuppression. Curr Opin Organ Transplant. 2021 Feb 1;26(1):91-96. doi: 10.1097/MOT.0000000000000844.
PubMed 33332922
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized-withdrawal, Placebo-controlled Study to Evaluate the Efficacy and Safety of Human Plasma-derived C1-esterase Inhibitor as add-on to Standard of Care for the Treatment of Refractory Antibody Mediated Rejection in Adult Renal Transplant Recipients
- ClinicalTrials.gov ID
- NCT03221842
- Acronym / sponsor ID
- CSL842_3001
- Conditions
- Antibody-mediated Rejection
- Keywords
- Antibody-mediated kidney transplant rejection, Renal
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early due to futility of enrolment and not for safety reasons.
- Enrolment
- 63 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Study start
- 6 Nov 2017 (actual)
- Primary completion
- 20 Jan 2021 (actual)
- Study completion
- 20 Jan 2021 (actual)
- First posted
- 19 Jul 2017 (actual)
- Results
- Posted 18 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a double-blind, randomized-withdrawal, placebo-controlled study in kidney transplant patients with AMR to evaluate the efficacy and safety of human plasma-derived C1-esterase inhibitor as add-on to standard of care (IVIG).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized-withdrawal
| Arm | Type | Receives |
|---|---|---|
| C1-INH | Experimental | Drug: C1-esterase inhibitorC1-esterase inhibitor |
| Placebo | Placebo comparator | Drug: PlaceboExcipients of C1-INH plus albumin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female at least 18 years of age;
- Evidence of at least one donor-specific antibody (DSA);
- Recipient of a kidney transplant;
- Achieved a steady-state, post-transplant eGFR ≥ 40 mL/min/1.73 m2 within 60 days of post-transplant OR a 50% increase in urine output with a 50% decrease in serum creatinine over the first 7 days post-transplant in subjects with slow or delayed graft function;
- Acute AMR.
Key exclusion criteria (8 listed)
- Recipient of an en bloc kidney transplant;
- Current active hepatitis C virus (HCV) infection;
- Active bacterial or fungal infection;
- Ongoing dialysis >2 weeks;
- Known congenital bleeding or coagulopathy disorder;
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 |
|---|---|---|
| C1-esterase inhibitorAlso: C1-INHC1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution | Drug | C1-INH |
| PlaceboExcipients of C1-INH plus albumin | Drug | Placebo |
Primary outcome
Percent of Participants With Loss-of-response During Treatment Period 2 (TP2)
Time frame: Up to 38 weeks
Loss of response is defined as 1 of the following, whichever occurs first: * Decline in Estimated Glomerular Filtration Rate (eGFR), or * Allograft failure, or * Subject death by any cause.
13 secondary outcomes
Number of Participants With All-cause Allograft Failure During TP2
Time frame: Up to 38 weeks
Percent of Participants With All-cause Allograft Failure During TP2
Time frame: Up to 38 weeks
Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of Treatment Period 1 (TP1)
Time frame: Baseline and 13 weeks
Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of TP2
Time frame: Baseline and 38 weeks
The Rate of Change of eGFR During TP2 as Defined by the Slope of the Mean Regression of eGFR Over Time at End of TP2
Time frame: Up to 38 weeks
Time to All-cause Allograft Failure Through the Follow up Period
Time frame: Up to approximately 208 weeks
Number of Responders at the End-of-TP1
Time frame: Up to 13 weeks
Percent of Responders at the End-of-TP1
Time frame: Up to 13 weeks
Proportion of Subjects Surviving Through the Follow-up Period
Time frame: Up to approximately 208 weeks
Percent of Participants With Any Adverse Event (AE) Assessed as Related to Investigational Product
Time frame: Up to approximately 42 weeks after the time of first investigational product administration
Mean Pre-dose C1-esterase Inhibitor Functional Activity
Time frame: Up to 13 weeks
Area Under the Plasma Concentration Time Curve (AUC0-t) for C1-INH Functional Activity
Time frame: Up to 72 hours after post-dose on Day 10 and on Day 77 of Period 1
Time to Maximum Plasma Concentration (Tmax) for C1-INH Functional Activity
Time frame: Up to 72 hours after post-dose on Day 10 and on Day 77 of Period 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33332922Viklicky O, Slatinska J, Novotny M, Hruba P. Developments in immunosuppression. Curr Opin Organ Transplant. 2021 Feb 1;26(1):91-96. doi: 10.1097/MOT.0000000000000844.
- 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.
Program Director study director
CSL Behring
26 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing C1-esterase inhibitor in people with Antibody-mediated Rejection, run by CSL Behring at 26 sites in 7 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 5 inclusion and 8 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 29 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, France, Spain, Belgium, Germany and 2 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. 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 18 Jan 2022). 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 of Participants With Loss-of-response During Treatment Period 2 (TP2) (time frame: Up to 38 weeks). 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 NCT03221842, 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 29 Jul 2022.