Safety, Tolerability and Efficacy of AntiBKV as Treatment of BKV Infection in Kidney Transplant Recipients
Purpose
The purpose of this study is to evaluate the safety, tolerability, and efficacy of AntiBKV in reducing BKV DNAemia and progression to biopsy-confirmed BKVAN in Kidney Transplant Recipients (KTRs). The study includes two parts. The phase II part will evaluate the safety of AntiBKV in KTRs and establish proof of concept. The phase III part will assess the efficacy of AntiBKV in KTRs. For both the phase II and phase III parts, participants will be randomized to receive either four doses of AntiBKV or four doses of placebo (every 4 weeks). Both the phase II and phase III parts will follow identical study assessments and schedules for participants. Based on an interim analysis after phase II total sample size for the trial will be defined. Eligible participants will receive an intravenous infusion of the investigational medicinal product (IMP) that will be administered four times at a 4-week interval. Seven days following the first IMP administration, participants will be re-evaluated for BKV DNAemia and, if appropriate, changes of immunosuppressive treatment will be started. After administration of the final dose, participants will return as out participants for periodic safety, BKV DNAemia, and PK follow-up assessments until the end of the trial visits, 26 weeks post last IMP application. Regular kidney biopsies will be performed at baseline (prior to infusion) and on Day 141 (8 weeks after full dosing). An additional biopsy will be taken on Day 267 (optional) and as clinically indicated.
Condition
- BK Viremia; BKV DNAemia
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Male or female aged 18 years or older 2. Kidney transplantation within 24 months prior to enrollment 3. Kidney transplant recipient with first-time BKV DNAemia (evaluated during routine clinical monitoring by the local laboratory and acknowledged by a physician within 4 months prior to Day 1). BKV DNAemia is either defined by BKV-DNAemia of one time >10,000 copies/mL, or >1,000 copies/mL sustained for at least one week (confirmed by 2 consecutive measurements. Note: The second, most recent laboratory value must be acknowledged by a physician within 4 months prior to Day 1) 4. Kidney transplant recipients with adequate and/or stable allograft function as indicated by estimated glomerular filtration rate ((e)GFR) ≥ 30 mL/min 5. Female subjects (if of childbearing potential) must agree to use adequate and reliable contraceptive measures throughout their participation in the trial. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies 6. Ability to provide written informed consent
Exclusion Criteria
- Patients with previous diagnosis of BK viremia (defined as one time >10,000 copies/mL, or >1,000 copies/mL sustained for at least one week (confirmed by 2 consecutive measurements) since last kidney transplant 2. Known hypersensitivity to any component of the investigational medicinal product (IMP) 3. Transplanted kidney disease with an estimated glomerular filtration rate ((e)GFR) < 30 mL/minute at screening 4. Uncontrolled acute or chronic infection other than BK virus (BKV) infection at screening which might interfere with study participation at the discretion of the investigator 5. Recipients who are treated or planned to be treated with a mammalian Target of Rapamycin (mTOR) inhibitor or belatacept as part of their immunosuppression regimen post-transplantation at the time of enrollment and during the study period. 6. Recipients who are treated or planned to be treated during study participation with leflunomide at the time of enrollment and during the study period. 7. Recipients who in the opinion of the investigator are likely to require antibody-depletion therapy during trial participation. Antibody-depleting therapies include but are not necessarily limited to plasmapheresis, immunoadsorption, and intravenous immunoglobulins (IVIg) 8. Recipients with active kidney transplant rejection or focal segmental glomerulosclerosis (FSGS) shown by renal biopsy 9. Recipients who have medical conditions or receive concomitant medications that prevent the recipient from undergoing allograft biopsy 10. Recipients with known donor-specific antibodies (DSA) (de novo or pre-transplantation). Kidney transplant recipients with low-level pretransplant DSAs (<1000 mean fluorescence intensity (MFI) can be includred if no impact on the study assessments is expected by the discretion of the investigator 11. Recipients with extremely high BK virus (BKV)-DNAemia (>10,000,000 copies/mL) or hemorrhagic cystitis 12. Recipients who in the opinion of the investigator are likely to develop recurrent native kidney disease (e.g. immunoglobulin A [IgA] nephritis, focal segmental glomerulosclerosis [FSGS], C3 glomerulonephritis) 13. Recipients with a functionally significant ureteral stricture 14. Pregnant or nursing (lactating) women 15. Known current active or latent TB or any history, in the opinion of the investigator, that confers a risk of reactivation of latent TB and precludes the use of conventional immunosuppression 16. History of splenectomy or asplenia 17. Any condition, that in the opinion of the investigator, would interfere with the evaluation of the investigational product or interpretation of the participant safety data or study results 18. History of malignancy within the past 5 years, except completely excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ at least 2 years prior to screening 19. Participation in another interventional clinical trial during trial participation or within 30 days prior to the investigational medicinal product (IMP) dosing or planned dosing 20. History of alcoholism or drug addiction within 1 year of screening. Substance use disorder will be an exclusion criterion, at investigator's discretion
Study Design
- Phase
- Phase 2/Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Parallel assignment Randomized
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Anti-BK polyomavirus (AntiBKV) |
1,000mg Anti-BK polyomavirus (AntiBKV) intravenous infusion every 4 weeks (4 doses) |
|
|
Placebo Comparator Placebo |
Placebo intravenous infusion every 4 weeks (4 doses) |
|
Recruiting Locations
Baltimore, Maryland 21201
More Details
- Status
- Recruiting
- Sponsor
- Memo Therapeutics AG