Kidney TransplantationPhase 3InAuGuRALNCT02374736
Effect of Privigen Against Graft Loss
A Phase 3 study testing Privigen (Human normal immunoglobulin G (IgG > 98 % purity)) in people with Kidney Transplantation, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The principal objective of this pilot study is to determine whether the progression of chronic antibody-mediated rejection (ABMR) could be minimized by the post-transplant administration of high dose of Intravenous Immunoglobulins (IVIg). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- Privigen (Human normal immunoglobulin G (IgG > 98 % purity))
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteFrance
- Study dates
- 5 Feb 2016to 9 May 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Deceased donor kidney transplant recipients between 3 and 12 months post transplantation.
- At least 18 years old.
- With stable renal function assessed within 30 days before inclusion and with delta GFR (MDRD) lower than 10 ml/min (latest result versus the average of the two previous values).
- Presence of at least one circulating HLA-DSA class I or II against HLA-A, -B, -DR, -DQ, -DP, -C (MFI ≥ 1000) as assessed by Luminex single antigen technique within 30 days before inclusion.
- With histological markers of active antibody-mediated injury as defined by the microcirculation inflammation score (g, ptc scores defined by current Banff criteria) on protocol biopsies performed at M3 or M12 post-transplantation, or if required between three and twelve months post transplantation (1 ≤ g+ptc ≤ 3).
- Able to comply with the study procedures and follow the study instructions.
- Who have read the information sheet and signed the informed consent form.
Who cannot join
- Acute renal dysfunction at the time of enrolment: decrease of GFR higher or equal to 10 ml/min (latest result versus the average of the two previous values), or 20% increase of serum creatinine.
- Previous episode of ABMR.
- Previous treatment with plasmapheresis, IVIg, within 2 months prior to inclusion
- 3b. Previous treatment with rituximab, eculizumab or bortezomib within 1 year prior to inclusion
- 4. Major lesions of active antibody-mediated injury, as defined by Banff criteria, such as g + ptc >3 or chronic transplant glomerulopathy (cg>0).
- 5. History of cardiac insufficiency (New York Heart Association [NYHA] III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease, congestive heart failure or severe hypertension.
Show all 14Show fewer
- 6. History of thrombotic episodes (deep vein thrombosis, myocardial infarction, cerebrovascular accident).
- 7. Known allergic or other severe reactions to blood products including intolerability to previous IVIg (i.e. severe headache, hypersensitivity, intravascular hemolysis).
- 8. Subject with a known deficit in IgA, with antibodies against IgA. 9. Known hyperprolinemia.
- 10. Ongoing HIV, hepatitis C and hepatitis B infection.
- 11. Any condition (including alcohol, drug or medication abuse) that is likely to interfere with evaluation of the study product or satisfactory conduct of the study.
- 12. Not able to comply with study procedures and treatment regimen.
- 13. Pregnant or lactating women or women of childbearing potential without effective method of contraception (oral contraceptive pill, intra-uterine contraceptive device, contraceptive implant or condom).
- 14. Participation in any other study involving investigational products, concomitantly or within 30 days prior to entry in the study.
Trial locations and contacts
1 site in 1 country.
France1 site
Service de Néphrologie et transplantation rénale - HU Saint-Louis
Paris, Île-de-France Region, 75010
About this study
Official title: A Pilot Study on the Effect of Privigen Against Graft Loss: Interventional Study of Kidney Transplant Recipients at Risk for Graft Loss Through Antibody-mediated Rejection
The principal objective of this pilot study is to determine whether the progression of chronic antibody-mediated rejection (ABMR) could be minimized by the post-transplant administration of high dose of Intravenous Immunoglobulins (IVIg).
We test the hypothesis that repetitive IVIg administration reduces or stabilize the progressive loss of transplant function and the evolution to chronic ABMR in stable kidney transplant patients with HLA-DSA developed post-transplantion (de novo HLA-DSA) and concomitant humoral graft injury.
Read the detailed description
The aim of this study is to assess the effect of IVIg associated to conventional immunosuppressive treatment in 15 stable transplant recipients with post-transplant de novo HLA-DSA and histological humoral lesions.
The study will include 2 periods:
- Treatment period,
- Follow-up period. The treatment will start the day of inclusion (M0): Privigen will be given as 2 g/kg for 2 days/month for 6 months (maximum dose: 80 g/day).
Evaluation at the end of treatment will take place on month 6 (M6). Evaluation at the end of follow up will take place on month 12 (M12).
Blood and urine samples will be collected on day of inclusion (M0), before each infusion of Privigen, at M6 and M12 for biological analysis (serum creatinine, glomerular filtration rate, proteinuria).
Blood samples will be collected on day of inclusion (M0), at M6 and M12 for immunoassay (HLA-DSA mean fluorescence intensity).
Blood sample will be collected on day of inclusion (M0) to provide a DNA bank. Blood samples will be collected on day of inclusion (M0), before each infusion of Privigen and at M6 for IgG dosage.
Blood samples will be collected on day of inclusion (M0), before each infusion of Privigen, at M6 and M12 to provide a serum bank.
Blood samples will be collected on day of inclusion (M0), before each infusion of Privigen, at M6 and M12 for haematology, blood chemistry and Coombs test.
Histological characteristics (kidney biopsies) will be performed on M0 and M6. The M6 biopsy is specifically requested by the protocol and differs from the usual practice, where it is usually performed at M12 post transplantation.
Infectious and clinical events (deceased patients, graft loss, acute biopsy-proven rejection episode and infectious diseases) will be recorded during the follow-up period.
Histology of for-cause biopsies will be performed according to center practice. We recommend a graft biopsy for patients with acute allograft dysfunction (20% increase of creatinine) without current evident causes of graft dysfunction.
The maximum study duration for a subject, between inclusion and follow-up visits, will be 12 months and the estimated length of time needed to complete the entire study (from enrolment of the first subject to completion of the last subject) 18 months.
- Conditions
- Kidney Transplantation
- Being tested
- Privigen (Human normal immunoglobulin G (IgG > 98 % purity))
- Keywords
- recipients, Subclinical Antibody-mediated rejection (ABMR), Intravenous immunoglobulins (IVIg), Donor-specific antibodies (DSA)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Privigen (Human normal immunoglobulin G (IgG > 98 % purity))Drug
Privigen (CSL Behring AG, Bern, Switzerland) 10% liquid human IgG for intravenous administration, 2 g/kg, given as 2 g/kg for 2 days/month for 6 months (maximum dose: 80 g/day).
Privigen will be provided in vials containing 10 g IgG in 100 mL.
| Study group | Role | What they receive |
|---|---|---|
| Human normal immunoglobulin G (IgG > 98 % purity) | Experimental | All subjects will be treated for 6 months. The treatment will start the day of inclusion (M0).
Privigen will be given as 2 g/kg for 2 days/month. The maximum daily dose authorized will be 80g.
The infusion rates are the recommended rates for Privigen in other indications and are in line with the market authorization for Privigen:
* Infusions should start at a rate of 0.5 mg/kg/min (0.005 mL/kg/min; 0.3 mL/kg/h; 30 mg/kg/h). If well tolerated within 30 min, the rate can be increased in a first step to 1.0 mg/kg/min (0.01 mL/kg/min; 0.6 mL/kg/h; 60 mg/kg/h) for another 30 min.
* If well tolerated, a stepwise increase to a maximum of 8 mg/kg/min (0.08 mL/kg/min; 4.8 mL/kg/h; 480 mg/kg/h) is allowed at the discretion of the investigator. Receives: Drug: Privigen (Human normal immunoglobulin G (IgG > 98 % purity)) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Graft function: estimation of change from baseline Glomerular Filtration Rate (GFR) using MDRD
using Modification of Diet in Renal Disease (MDRD) equation at M6
Measured: at months 6
Graft function: estimation of change from baseline Glomerular Filtration Rate (GFR) using MDRD
using Modification of Diet in Renal Disease (MDRD) equation at M12
Measured: at months 12
Secondary outcomes (5)
Change of proteinuria from baseline
Change of proteinuria value at M6 and M12 compared to M0. The proteinuria is measured from blood sample
Measured: months 6 and months 12
Change of HLA-DSA from baseline
The presence of HLA-DSA will be analyzed using Luminex single-antigen assays at M6 and M12 compared to M0. The HLA-DSA is measured from blood sample
Measured: months 6 and months 12
Change of Histological characteristics from baseline
A kidney biopsy will be performed at M6 and compared to M0
Measured: at months 6
IgG dosage
IgG dosage will be performed at M0, before each Privigen infusion and at M6
Measured: up to months 6
Infectious events reported during the study period
Infectious events will be reported from M0 to M12.
Measured: up to months 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2015 (estimated)
- Study start5 Feb 2016
- Primary completion9 Mar 2018
- Study completion9 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- CSL Behring, Association ASLUMARE
- Responsible party
- Sponsor
- Investigators
- Denis GLOTZ, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02374736
- Sponsor's protocol ID
- P140501
- Other IDs
- 2014-003707-30, 2014
- Acronym
- InAuGuRAL
- Status last verified
- Feb 2021
- First submitted
- 20 Jan 2015
- Last updated
- 9 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study on the Effect of Privigen Against Graft Loss: Interventional Study of Kidney Transplant Recipients at Risk for Graft Loss Through Antibody-mediated Rejection
- ClinicalTrials.gov ID
- NCT02374736
- Acronym / sponsor ID
- InAuGuRAL / P140501
- Conditions
- Kidney Transplantation
- Keywords
- recipients, Subclinical Antibody-mediated rejection (ABMR), Intravenous immunoglobulins (IVIg), Donor-specific antibodies (DSA)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- CSL Behring, Association ASLUMARE
- Study start
- 5 Feb 2016 (actual)
- Primary completion
- 9 Mar 2018 (actual)
- Study completion
- 9 May 2019 (actual)
- First posted
- 2 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The principal objective of this pilot study is to determine whether the progression of chronic antibody-mediated rejection (ABMR) could be minimized by the post-transplant administration of high dose of Intravenous Immunoglobulins (IVIg).
We test the hypothesis that repetitive IVIg administration reduces or stabilize the progressive loss of transplant function and the evolution to chronic ABMR in stable kidney transplant patients with HLA-DSA developed post-transplantion (de novo HLA-DSA) and concomitant humoral graft injury.
Detailed description
The aim of this study is to assess the effect of IVIg associated to conventional immunosuppressive treatment in 15 stable transplant recipients with post-transplant de novo HLA-DSA and histological humoral lesions.
The study will include 2 periods:
- Treatment period,
- Follow-up period. The treatment will start the day of inclusion (M0): Privigen will be given as 2 g/kg for 2 days/month for 6 months (maximum dose: 80 g/day).
Evaluation at the end of treatment will take place on month 6 (M6). Evaluation at the end of follow up will take place on month 12 (M12).
Blood and urine samples will be collected on day of inclusion (M0), before each infusion of Privigen, at M6 and M12 for biological analysis (serum creatinine, glomerular filtration rate, proteinuria).
Blood samples will be collected on day of inclusion (M0), at M6 and M12 for immunoassay (HLA-DSA mean fluorescence intensity).
Blood sample will be collected on day of inclusion (M0) to provide a DNA bank. Blood samples will be collected on day of inclusion (M0), before each infusion of Privigen and at M6 for IgG dosage.
Blood samples will be collected on day of inclusion (M0), before each infusion of Privigen, at M6 and M12 to provide a serum bank.
Blood samples will be collected on day of inclusion (M0), before each infusion of Privigen, at M6 and M12 for haematology, blood chemistry and Coombs test.
Histological characteristics (kidney biopsies) will be performed on M0 and M6. The M6 biopsy is specifically requested by the protocol and differs from the usual practice, where it is usually performed at M12 post transplantation.
Infectious and clinical events (deceased patients, graft loss, acute biopsy-proven rejection episode and infectious diseases) will be recorded during the follow-up period.
Histology of for-cause biopsies will be performed according to center practice. We recommend a graft biopsy for patients with acute allograft dysfunction (20% increase of creatinine) without current evident causes of graft dysfunction.
The maximum study duration for a subject, between inclusion and follow-up visits, will be 12 months and the estimated length of time needed to complete the entire study (from enrolment of the first subject to completion of the last subject) 18 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Human normal immunoglobulin G (IgG > 98 % purity) | Experimental | Drug: Privigen (Human normal immunoglobulin G (IgG > 98 % purity))All subjects will be treated for 6 months. The treatment will start the day of inclusion (M0). Privigen will be given as 2 g/kg for 2 days/month. The maximum daily dose authorized will be 80g. The infusion rates are the recommended rates for Privigen in other indications and are in line with the market authorization for Privigen: * Infusions should start at a rate of 0.5 mg/kg/min (0.005 mL/kg/min; 0.3 mL/kg/h; 30 mg/kg/h). If well tolerated within 30 min, the rate can be increased in a first step to 1.0 mg/kg/min (0.01 mL/kg/min; 0.6 mL/kg/h; 60 mg/kg/h) for another 30 min. * If well tolerated, a stepwise increase to a maximum of 8 mg/kg/min (0.08 mL/kg/min; 4.8 mL/kg/h; 480 mg/kg/h) is allowed at the discretion of the investigator. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Deceased donor kidney transplant recipients between 3 and 12 months post transplantation.
- At least 18 years old.
- With stable renal function assessed within 30 days before inclusion and with delta GFR (MDRD) lower than 10 ml/min (latest result versus the average of the two previous values).
- Presence of at least one circulating HLA-DSA class I or II against HLA-A, -B, -DR, -DQ, -DP, -C (MFI ≥ 1000) as assessed by Luminex single antigen technique within 30 days before inclusion.
- With histological markers of active antibody-mediated injury as defined by the microcirculation inflammation score (g, ptc scores defined by current Banff criteria) on protocol biopsies performed at M3 or M12 post-transplantation, or if required between three and twelve months post transplantation (1 ≤ g+ptc ≤ 3).
Key exclusion criteria (14 listed)
- Acute renal dysfunction at the time of enrolment: decrease of GFR higher or equal to 10 ml/min (latest result versus the average of the two previous values), or 20% increase of serum creatinine.
- Previous episode of ABMR.
- Previous treatment with plasmapheresis, IVIg, within 2 months prior to inclusion
- 3b. Previous treatment with rituximab, eculizumab or bortezomib within 1 year prior to inclusion
- 4. Major lesions of active antibody-mediated injury, as defined by Banff criteria, such as g + ptc >3 or chronic transplant glomerulopathy (cg>0).
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 |
|---|---|---|
| Privigen (Human normal immunoglobulin G (IgG > 98 % purity))Privigen (CSL Behring AG, Bern, Switzerland) 10% liquid human IgG for intravenous administration, 2 g/kg, given as 2 g/kg for 2 days/month for 6 months (maximum dose: 80 g/day). Privigen will be provided in vials containing 10 g IgG in 100 mL. | Drug | Human normal immunoglobulin G (IgG > 98 % purity) |
Primary outcome
Graft function: estimation of change from baseline Glomerular Filtration Rate (GFR) using MDRD
Time frame: at months 6
using Modification of Diet in Renal Disease (MDRD) equation at M6
Graft function: estimation of change from baseline Glomerular Filtration Rate (GFR) using MDRD
Time frame: at months 12
using Modification of Diet in Renal Disease (MDRD) equation at M12
5 secondary outcomes
Change of proteinuria from baseline
Time frame: months 6 and months 12
Change of HLA-DSA from baseline
Time frame: months 6 and months 12
Change of Histological characteristics from baseline
Time frame: at months 6
IgG dosage
Time frame: up to months 6
Infectious events reported during the study period
Time frame: up to months 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2021.
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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.
Denis GLOTZ, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Privigen (Human normal immunoglobulin G (IgG > 98 % purity)) in people with Kidney Transplantation, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 7 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: finished, as of the sponsor's last update on 9 Mar 2021. 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 France. 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Graft function: estimation of change from baseline Glomerular Filtration Rate (GFR) using MDRD (time frame: at months 6). 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?
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 9 Mar 2021.