Kidney Transplantation in Highly Sensitized PatientsPhase 2NCT05049850
A Study to Investigate DSA Rebound in Patients Treated With Imlifidase Prior to Transplantation
A Phase 2 study testing Imlifidase in people with Kidney Transplantation in Highly Sensitized Patients, run by Hansa Biopharma AB at 1 site in United States.
Trial summary
The purpose of this study is to assess whether imlifidase in combination with bortezomib, belatacept, rituximab and IVIg can suppress donor specific antibodies (DSA) and the occurrence of antibody-mediated rejection (AMR) in highly sensitized patients with chronic kidney disease with a positive crossmatch towards… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Kidney Transplantation in Highly Sensitized Patients
- What is being tested?
- Imlifidase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Dec 2022to 8 May 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed Informed Consent obtained before any trial-related procedures
- Male or female age 18 to 70 years at the time of screening
- Highly sensitized patients registered on the UNOS waiting list for kidney transplantation, with either of the following:
- cPRA ≥ 99.9%
- cPRA ≥ 98% and have been in kidney paired donation or kidney paired exchange programs for at least 1 year
- A positive crossmatch towards a living donor
- Willingness and ability to comply with the protocol
Who cannot join
- Previous treatment with imlifidase
- Previous high dose IVIg treatment (2 g/kg) within 28 days prior to imlifidase treatment
- Breast-feeding or pregnancy
- Women of child-bearing potential not willing or able to practice FDA-approved forms of contraception. Two medically acceptable methods of highly effective contraception must be used for the duration of the study (e.g. oral, transdermal, intravaginal, injectable or implantable contraceptive; intrauterine device; intrauterine hormone-releasing system; vasectomized partner; bilateral tubal occlusion; or double-barrier method). For a woman to be considered postmenopausal this ascertainment must be made according to medical records and clinical history and may be aided by measurement of elevated postmenopausal serum gonadotropin levels (FSH).
- ABO blood group incompatible transplantations (A2 and A2B kidneys will not be accepted for B recipients)
- Positive serology for HIV
Show all 19Show fewer
- Clinical signs of HBV, HCV, CMV, or EBV infection
- EBV seronegative or with unknown EBV serostatus
- Positive SARS-CoV-2 tests at any time point from screening to transplantation
- Active tuberculosis
- Ongoing serious infections as judged by the investigator
- Severe other conditions requiring treatment and close monitoring e.g. cardiac failure ≥ grade 4 (New York Heart Association), unstable coronary disease or oxygen dependent respiratory disease
- A history of a proven hypercoagulable condition
- Present, or history of, thrombotic thrombocytopenic purpura (TTP) or known familial history of TTP
- Intake of investigational drugs (other than imlifidase) within 5 half-lives
- Contemporaneous participation in a medical device study
- Known allergy/sensitivity (except local reactions) to imlifidase or to any drug (or the excipients) specified in the protocol
- Known mental incapacity or language barriers precluding adequate understanding of the Informed Consent information and the trial activities
- Inability by the judgement of the investigator to participate in the trial for any other reason
Trial locations and contacts
1 site in 1 country.
United States1 site
NYU Langone Health Transplant Institute
New York, New York, 10016
About this study
Official title: An Open Label, Phase II Study to Investigate DSA Rebound in Patients With a Positive Crossmatch, Made Transplantable With Imlifidase
The purpose of this study is to assess whether imlifidase in combination with bortezomib, belatacept, rituximab and IVIg can suppress donor specific antibodies (DSA) and the occurrence of antibody-mediated rejection (AMR) in highly sensitized patients with chronic kidney disease with a positive crossmatch towards their living donor during a period of 3 months from transplantation.
Read the detailed description
Imlifidase is an immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that is highly specific for IgG. The cleavage of IgG generates one F(ab')2- and one homodimeric Fc-fragment and efficiently neutralizes Fc-mediated activities of IgG. Clinical studies with imlifidase have demonstrated that the treatment enables transplantation in patients otherwise highly unlikely to be transplanted, by converting a positive crossmatch to a negative.
However, as with other desensitization methods, DSA tend to reappear within weeks after treatment and transplantation, which may cause AMR and increased risk of graft loss. In this study, treatment with imlifidase in combination with approved drugs that prevent or suppress DSA rebound by targeting antibody-producing plasma-cells and their B-cell precursors is suggested. These drugs include (i) bortezomib, a proteasome inhibitor which has activity against mature plasma cells, the source of DSA, (ii) belatacept, a fusion protein which is crucial in blocking T-cell co-stimulation and which is effective in reducing de novo DSA generation in humans, (iii) rituximab, an anti-CD20 monoclonal antibody that targets B-cells and which is an immunomodulatory agent, and (iv) intravenous immunoglobulin (IVIg) which is commonly used in desensitization regimens and for the treatment of AMR.
After being informed about the study and potential risks, all patients giving written informed consent will undergo a 2-week screening period to determine eligibility for study entry. Patients who meet the eligibility requirements will then start treatment with belatacept and bortezomib about 3 weeks prior to the imlifidase infusion and transplantation. Rituximab will be initiated 8 days after transplantation and IVIg 10 days after transplantation. Induction and maintenance immunosuppression will also be administered. The patients will be hospitalized for approximately 2 weeks following transplantation and after that 9 follow-up visits to the clinic will take place up to 6 months after transplantation.
- Being tested
- Imlifidase
- Keywords
- Highly sensitized, Kidney transplantation, Renal transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImlifidaseDrug
Also called IdeS, HMED-IdeS
Imlifidase is an immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that is highly specific for IgG.
| Study group | Role | What they receive |
|---|---|---|
| Imlifidase | Experimental | Imlifidase is administered intravenously as one dose of 0.25 mg/kg over 15 minutes within the 24-hour period prior to transplantation. (A second dose may be given if the crossmatch test at 4 hours after the first dose remains positive.) Receives: Drug: Imlifidase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Patients With DSA Rebound
The recurrence of DSA may cause AMR and increased risk of graft loss. Due to the early termination of the trial the primary endpoint was assessed as the incidence of DSA rebound of either immunodominant or total DSA to a mean fluorescence intensity (MFI) level that was ≥50% of the pre-imlifidase value up to 3 months after transplantation (trial day 91).
Measured: Up to 3 months after transplantation
Secondary outcomes (20)
Proportion of Patients With Kidney Biopsy Proven AMR
The standardized international Banff classification 2019 for assessment of renal allograft biopsies will be used to assess AMRs reported from the study based on for cause and protocol biopsies.
Measured: Up to 6 months after transplantation
Proportion of Patient With DSA Rebound
See description to primary outcome measure
Measured: Up to 6 months after transplantation
Proportion of Patients With Negative FCXM
Imlifidase is highly efficacious in converting a positive crossmatch to a negative
Measured: Up to 24 hours after imlifidase treatment
Levels of DSA
Analysis of DSAs before and after imlifidase will be done. The mean fluorescence intensity (MFI) will be presented for the individual patients' DSAs.
Measured: Within 4 hours before imlifidase until Day 181
Levels of Complement Binding (C1q) DSA
Analysis of C1q DSAs before and after imlifidase will be done. The mean fluorescence intensity (MFI) will be presented for the individual patients' C1q DSAs.
Measured: Within 4 hours before imlifidase until Day 181
Number of Participants With Graft Survival
Graft survival will be summarized by end of trial.
Measured: 6 months after transplantation
Patients Survival
Patient survival will be summarized by end of trial.
Measured: 6 months after transplantation
Number of Participants With Adverse Events (AEs)
Safety is assessed as type, frequency and intensity of adverse events (AEs)/serious adverse events (SAEs) including clinically relevant changes in clinical laboratory tests, vital signs and ECG)
Measured: Up to 6 months after transplantation
Kidney Function Assessed by Creatinine
P-creatinine is a measure of kidney function.
Measured: Up to 6 months after transplantation
Kidney Function Assessed by Estimated Glomerular Filtration Rate (eGFR)
Estimated glomerular filtration rate (eGFR) is a measure of kidney function. eGFR will be calculated as described by the modification of diet in renal disease (MDRD) equation.
eGFR for a kidney with normal function is 90 mL/min/1.73m2. Kidney disease is characterized by a decreased eGFR value.
Measured: Up to 6 months after transplantation
Kidney Function Assessed by Protein/Creatinine Ratio in Urine
The protein/creatinine ratio in urine is a measure of kidney function. Will be measured unless patients are anuric.
Measured: Up to 6 months after transplantation
Imlifidase Pharmacokinetics (AUC)
AUC = Area under the imlifidase plasma concentration versus time curve
Measured: Within 4 hours before imlifidase dose until Day 15
Imlifidase Pharmacokinetics (Cmax)
Cmax = Maximum observed plasma concentration of imlifidase following dosing
Measured: Within 4 hours before imlifidase dose until Day 15
Imlifidase Pharmacokinetics (Tmax)
tmax = Time point for maximum observed plasma concentration of imlifidase following dosing
Measured: Within 4 hours before imlifidase dose until Day 15
Imlifidase Pharmacokinetics (t1/2)
t1/2 = Terminal half-life of imlifidase, the time taken for concentration of imlifidase to decrease from its maximum concentration (Cmax) to half of Cmax in the blood plasma.
t1/2 alpha = alpha phase (distribution/elimination) half-life, an initial phase of rapid decrease in plasma concentration.
t1/2 beta = beta phase (elimination) half-life, a phase of gradual decrease in plasma concentration after the alpha phase.
Measured: Within 4 hours before imlifidase dose until Day 15
Imlifidase Pharmacokinetics (CL)
CL = Clearance of imlifidase
Measured: Within 4 hours before imlifidase dose until Day 15
Imlifidase Pharmacokinetics (Vz)
Vz = Apparent volume of distribution during terminal phase
Measured: Within 4 hours before imlifidase dose until Day 15
Pharmacodynamics
Concentration of IgG in patient serum will be measured. Scoring of IgG fragments will be done.
Measured: Within 4 hours before imlifidase dose until Day 10
Anti-drug Antibodies (ADA) Levels
Immunogenicity towards imlifidase will be assessed by the measurement of ADA levels in patient serum using a customized ImmunoCAP analysis.
Measured: Up to 6 months after imlifidase
Change in Patient-reported Life Participation, as Measured PROMIS-SF-8a
The PROMIS Social Health domain "Ability to participate in social roles \& activities PROMIS-SF-8" will be used as a measure of the patients' health related quality of life.
Measured: At screening and Day 181
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2021
- Study start16 Dec 2022
- Primary completion5 Feb 2024
- Study completion8 May 2024
Why it stopped: Company decision, not due to any safety reason
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Kidney Transplantation in Highly Sensitized PatientsStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hansa Biopharma AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Operations, Study director, Hansa Biopharma AB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05049850
- Sponsor's protocol ID
- 18-HMedIdeS-16
- Status last verified
- Oct 2025
- First submitted
- 9 Sep 2021
- Last updated
- 21 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Phase II Study to Investigate DSA Rebound in Patients With a Positive Crossmatch, Made Transplantable With Imlifidase
- ClinicalTrials.gov ID
- NCT05049850
- Acronym / sponsor ID
- 18-HMedIdeS-16
- Keywords
- Highly sensitized, Kidney transplantation, Renal transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company decision, not due to any safety reason
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Hansa Biopharma ABIndustry (pharma, biotech, devices)
- Study start
- 16 Dec 2022 (actual)
- Primary completion
- 5 Feb 2024 (actual)
- Study completion
- 8 May 2024 (actual)
- First posted
- 20 Sep 2021 (actual)
- Results
- Posted 17 Mar 2025
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 study is to assess whether imlifidase in combination with bortezomib, belatacept, rituximab and IVIg can suppress donor specific antibodies (DSA) and the occurrence of antibody-mediated rejection (AMR) in highly sensitized patients with chronic kidney disease with a positive crossmatch towards their living donor during a period of 3 months from transplantation.
Detailed description
Imlifidase is an immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that is highly specific for IgG. The cleavage of IgG generates one F(ab')2- and one homodimeric Fc-fragment and efficiently neutralizes Fc-mediated activities of IgG. Clinical studies with imlifidase have demonstrated that the treatment enables transplantation in patients otherwise highly unlikely to be transplanted, by converting a positive crossmatch to a negative.
However, as with other desensitization methods, DSA tend to reappear within weeks after treatment and transplantation, which may cause AMR and increased risk of graft loss. In this study, treatment with imlifidase in combination with approved drugs that prevent or suppress DSA rebound by targeting antibody-producing plasma-cells and their B-cell precursors is suggested. These drugs include (i) bortezomib, a proteasome inhibitor which has activity against mature plasma cells, the source of DSA, (ii) belatacept, a fusion protein which is crucial in blocking T-cell co-stimulation and which is effective in reducing de novo DSA generation in humans, (iii) rituximab, an anti-CD20 monoclonal antibody that targets B-cells and which is an immunomodulatory agent, and (iv) intravenous immunoglobulin (IVIg) which is commonly used in desensitization regimens and for the treatment of AMR.
After being informed about the study and potential risks, all patients giving written informed consent will undergo a 2-week screening period to determine eligibility for study entry. Patients who meet the eligibility requirements will then start treatment with belatacept and bortezomib about 3 weeks prior to the imlifidase infusion and transplantation. Rituximab will be initiated 8 days after transplantation and IVIg 10 days after transplantation. Induction and maintenance immunosuppression will also be administered. The patients will be hospitalized for approximately 2 weeks following transplantation and after that 9 follow-up visits to the clinic will take place up to 6 months after transplantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imlifidase | Experimental | Drug: ImlifidaseImlifidase is administered intravenously as one dose of 0.25 mg/kg over 15 minutes within the 24-hour period prior to transplantation. (A second dose may be given if the crossmatch test at 4 hours after the first dose remains positive.) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Signed Informed Consent obtained before any trial-related procedures
- Male or female age 18 to 70 years at the time of screening
- Highly sensitized patients registered on the UNOS waiting list for kidney transplantation, with either of the following:
- A positive crossmatch towards a living donor
- Willingness and ability to comply with the protocol
Key exclusion criteria (19 listed)
- Previous treatment with imlifidase
- Previous high dose IVIg treatment (2 g/kg) within 28 days prior to imlifidase treatment
- Breast-feeding or pregnancy
- Women of child-bearing potential not willing or able to practice FDA-approved forms of contraception. Two medically acceptable methods of highly effective contraception must be used for the duration of the study (e.g. oral, transdermal, intravaginal, injectable or implantable contraceptive; intrauterine device; intrauterine hormone-releasing system; vasectomized partner; bilateral tubal occlusion; or double-barrier method). For a woman to be considered postmenopausal this ascertainment must be made according to medical records and clinical history and may be aided by measurement of elevated postmenopausal serum gonadotropin levels (FSH).
- ABO blood group incompatible transplantations (A2 and A2B kidneys will not be accepted for B recipients)
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 |
|---|---|---|
| ImlifidaseAlso: IdeS, HMED-IdeSImlifidase is an immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that is highly specific for IgG. | Drug | Imlifidase |
Primary outcome
Proportion of Patients With DSA Rebound
Time frame: Up to 3 months after transplantation
The recurrence of DSA may cause AMR and increased risk of graft loss. Due to the early termination of the trial the primary endpoint was assessed as the incidence of DSA rebound of either immunodominant or total DSA to a mean fluorescence intensity (MFI) level that was ≥50% of the pre-imlifidase value up to 3 months after transplantation (trial day 91).
20 secondary outcomes
Proportion of Patients With Kidney Biopsy Proven AMR
Time frame: Up to 6 months after transplantation
Proportion of Patient With DSA Rebound
Time frame: Up to 6 months after transplantation
Proportion of Patients With Negative FCXM
Time frame: Up to 24 hours after imlifidase treatment
Levels of DSA
Time frame: Within 4 hours before imlifidase until Day 181
Levels of Complement Binding (C1q) DSA
Time frame: Within 4 hours before imlifidase until Day 181
Number of Participants With Graft Survival
Time frame: 6 months after transplantation
Patients Survival
Time frame: 6 months after transplantation
Number of Participants With Adverse Events (AEs)
Time frame: Up to 6 months after transplantation
Kidney Function Assessed by Creatinine
Time frame: Up to 6 months after transplantation
Kidney Function Assessed by Estimated Glomerular Filtration Rate (eGFR)
Time frame: Up to 6 months after transplantation
Kidney Function Assessed by Protein/Creatinine Ratio in Urine
Time frame: Up to 6 months after transplantation
Imlifidase Pharmacokinetics (AUC)
Time frame: Within 4 hours before imlifidase dose until Day 15
Imlifidase Pharmacokinetics (Cmax)
Time frame: Within 4 hours before imlifidase dose until Day 15
Imlifidase Pharmacokinetics (Tmax)
Time frame: Within 4 hours before imlifidase dose until Day 15
Imlifidase Pharmacokinetics (t1/2)
Time frame: Within 4 hours before imlifidase dose until Day 15
Imlifidase Pharmacokinetics (CL)
Time frame: Within 4 hours before imlifidase dose until Day 15
Imlifidase Pharmacokinetics (Vz)
Time frame: Within 4 hours before imlifidase dose until Day 15
Pharmacodynamics
Time frame: Within 4 hours before imlifidase dose until Day 10
Anti-drug Antibodies (ADA) Levels
Time frame: Up to 6 months after imlifidase
Change in Patient-reported Life Participation, as Measured PROMIS-SF-8a
Time frame: At screening and Day 181
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Clinical Operations study director
Hansa Biopharma AB
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Imlifidase in people with Kidney Transplantation in Highly Sensitized Patients, run by Hansa Biopharma AB at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Oct 2025. 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 United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Mar 2025). 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?
Proportion of Patients With DSA Rebound (time frame: Up to 3 months after transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2025.