Phase 2
N=29
An Efficacy and Safety Study of Imlifidase in Treatment of Antibody-Mediated Rejection in Kidney Transplant Patients
Kidney Transplant Rejection
Bottom Line
View on ClinicalTrials.gov: NCT03897205 ↗Enrolled (actual)
29
Serious AEs
20.7%
Results posted
Feb 2024
Primary outcome: Primary: Maximum Reduction in Donor Specific Antibodies (DSA) Level During the 5 Days Following the Start of Treatment — 94; 36 percentage of maximum DSA reduction
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Imlifidase (Drug); Plasma Exchange (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hansa Biopharma AB
- Primary completion
- May 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Reduction in Donor Specific Antibodies (DSA) Level During the 5 Days Following the Start of Treatment |
94; 36 | — |
| SECONDARY Reduction in DSA Levels After Treatment |
91; -2; 94; -2; 92; 0 | — |
| SECONDARY Estimated Glomerular Filtration Rate (eGFR) Levels |
28.0; 21.0; 25.8; 23.5; 26.2; 25.7 | — |
| SECONDARY Urine Albumine/Creatinine Ratio |
626; 134; 669; 119; 815; 242 | — |
| SECONDARY Number of Patients With Graft Loss Within 180 Days of Treatment |
5; 0 | — |
| SECONDARY Number of Patients With Signs or no Signs of Transplant Glomerulopathy at Day 180 |
7; 4; 8; 6; 4; 0 | — |
| SECONDARY Number of Patients With Different Types of Kidney Histopathology Throughout the Trial |
7; 4; 0; 1; 5; 1 | — |
| SECONDARY Number of Patients With Resolved AMR as Assessed by Messenger Ribonucleic Acid (mRNA) Levels |
0; 0; 0; 0 | — |
| SECONDARY Number of Administered Plasma Exchange (PE) and Immunoadsorption (IA) Sessions |
20; 70; 18; 11; 0; 23 | — |
| SECONDARY Total Serum Immunoglobulin G (IgG) Levels Until Administration of Intravenous Immunoglobulin (IVIg) |
8.6; 7.9; 0.2; 4.3; 0.2; 4.6 | — |
| SECONDARY Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg |
19; 10; 0; 0; 0; 0 | — |
| SECONDARY DSA Functionality Determined by C1q Analysis Pre- and Post-treatment |
19827; 18848; 319; 15576; 5065; 11926 | — |
| SECONDARY Pharmacokinetic (PK) Profile of Imlifidase: Cmax |
4.3 | — |
| SECONDARY PK Profile of Imlifidase: Tmax |
0.6 | — |
| SECONDARY PK Profile of Imlifidase: t1/2 |
2.7; 39.7 | — |
| SECONDARY PK Profile of Imlifidase: AUC |
124 | — |
| SECONDARY PK Profile of Imlifidase: CL |
2.0 | — |
| SECONDARY PK Profile of Imlifidase: Volume of Distribution (V) |
0.64; 0.54 | — |
| SECONDARY Concentration of Anti-drug Antibodies (ADAs) |
6.7; 2.0; 15; 20; 49; 73 | — |
Summary
The purpose of this study was to investigate how efficiently the study medication imlifidase reduces the amount of donor specific antibodies (DSA) in comparison with plasma exchange (PE) therapy, in patients who have had an active or chronic active antibody mediated rejection (AMR) after being kidney transplanted. The purpose was also to investigate and compare safety for these two treatments.
Eligibility Criteria
Inclusion Criteria
- Signed Informed Consent obtained before any study-related procedures
- Willingness and ability to comply with the protocol
- Male and/or female donor kidney recipients age ≥18 years at the time of screening
- Presence of DSA(s)
- Meet the Banff 2017 criteria for active or chronic active AMR
- At least 25% rise in serum creatinine compared to last individual value taken prior to the AMR. Patients with delayed graft function and AMR within 10 days after transplant (confirmed by kidney biopsy) can be included regardless of serum creatinine level
- Women of child-bearing potential willing or able to use at least one highly effective contraceptive method throughout the study. In the context of this study, an effective method is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly
- Men willing to use double-barrier contraception from the first day of treatment until at least 2 months after the dose of imlifidase, if not abstinent
Exclusion Criteria
- Previous treatment with imlifidase
- Previous high dose IVIg treatment (2 g/kg) within 28 days prior to inclusion
- Lactating or pregnant females
- Significantly abnormal general serum screening lab results judged inappropriate for inclusion in the study by the investigator
- Intake of other investigational drugs within 5 half-lives (or similar) of the product prior to inclusion
- Clinically relevant active infection(s) as judged by the investigator
- Any condition that in the opinion of the investigator could increase the subject's risk by participating in the study such as severe immune deficiency and severe cardiac insufficiency [New York Heart Association (NYHA) Class IV] or severe uncontrolled heart disease
- Known allergy/sensitivity to imlifidase, IVIg and/or rituximab and the respective excipients
- Patient unable to tolerate treatment with plasmapheresis or immunoadsorption, as judged by the investigator
- Unsuitable to participate in the study for any other reason as judged by the investigator
- Positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection
- Current diagnosis or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP
Data sourced from ClinicalTrials.gov (NCT03897205). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.