A Study to Understand How a New, Unlicensed Drug (AIC468) Works, Compared With a Placebo, Against BK Virus in Patients Who Have Had a Kidney Transplant.

Official title

A Randomized, Adaptive, Double-Blind, Placebo-Controlled, Operationally Seamless Phase 2/3 Clinical Trial to Evaluate the Efficacy, Safety, and Tolerability of AIC263029 in the Treatment of BKV Infection in Kidney Transplant Recipients

Overview

The goal of this clinical trial is to learn if AIC263029 is safe and well tolerated in adult kidney transplant recipients with BK virus (BKV) in the blood (viremia). The study will also examine how the body processes AIC263029 and whether it lowers BKV levels in the blood. Researchers will compare AIC263029 to a placebo (a look-alike injection with no active drug). Participants will be assigned by chance to receive AIC263029 or placebo and will receive weekly injections under the skin for 4 weeks. Participants will have clinic visits and blood tests during treatment and follow-up to monitor safety and measure BKV levels, and will be followed for up to about 24 weeks after treatment.

Detailed description

This study is Part A (Phase 2a) of a randomized, double-blind, placebo-controlled clinical trial evaluating AIC263029 in adult kidney transplant recipients with BK virus (BKV) viremia. Part A is designed to assess safety and tolerability of multiple dose levels, characterize pharmacokinetics (PK), and explore antiviral activity based on changes in plasma BKV DNA.

In Part A, participants are enrolled into sequential dose cohorts. Within each cohort, participants are randomized in a 3:1 ratio to receive AIC263029 or matching placebo. Three dose levels are planned (100 mg, 200 mg, and 330 mg). Study drug is administered as subcutaneous injections once weekly, for a total of five injections over a 4-week treatment period. Up to three additional optional cohorts may be added based on emerging safety, PK, and antiviral activity data.

Participants undergo screening (up to approximately 30 days), followed by the 4-week treatment period and a follow-up period of up to approximately 24 weeks after the end of treatment. Safety evaluations include monitoring of treatment-emergent adverse events, adverse events of special interest (including injection site reactions and kidney transplant outcomes such as graft loss and acute/chronic rejection), and clinically significant changes in laboratory parameters, vital signs, and electrocardiograms. PK sampling is performed to estimate standard PK parameters. Antiviral activity is assessed by quantitative plasma BKV DNA measurements over time, including assessment of change from baseline and time to clinically meaningful reductions. Viral genotyping/resistance monitoring may be performed to assess baseline polymorphisms and potential treatment-emergent resistance.

Interventions

• Drug AIC263029
  AIC263029 supplied in vials for injection (110 mg/mL) and administered by subcutaneous injection; Part A uses weekly dosing over 4 weeks in planned dose cohorts (100 mg, 200 mg, 330 mg).
• Drug Placebo
  Matching placebo administered by subcutaneous injection

Primary outcome measures

• Frequency and severity of treatment-emergent adverse events (TEAEs) [Time frame: Day 1 to Day 30 of the dosing period.]

Eligibility criteria

Inclusion criteria

• Male or female aged 18 years or older
• Kidney transplantation within 12 months prior to randomization
• First episode of detectable BKV DNA in plasma since last kidney transplantation. As defined by either:

• positive BKV DNA test of one time >104 IU/mL and <106 IU/mL, within 30 days prior to randomization, or
• >103 IU/mL and ≤104 IU/mL sustained for at least 2 weeks (confirmed by at least 2 consecutive measurements), with the most recent measurement within 14 days prior to randomization.
• Female participants (if of childbearing potential) must agree to remain abstinent (refrain from heterosexual intercourse) or use at least one highly effective contraceptive method that result in a failure rate of <1% per year until the end of the trial.

Male participants must agree to refrain from donating sperm, and to remain abstinent (refrain from heterosexual intercourse) or use a condom with a female partner of childbearing potential until the end of the trial.

• Negative serum β-HCG (beta-human chorionic gonadotropin) test for women of child-bearing potential at Screening and a negative urine pregnancy test prior to randomization on Day 1.
• Able and willing to provide written informed consent and comply with trial protocol.

Exclusion criteria

• Known hypersensitivity to any component of the IMP
• Estimated glomerular filtration rate (\[e\]GFR) <30 mL/minute/1.73 m2 at screening
• Alanine transaminase (ALT) >2×upper limit of normal (ULN) or direct bilirubin >1.1×ULN (except Gilbert's Disease) at screening
• Uncontrolled participants who are treated or planned to be treated with an mTOR inhibitor or belatacept as part of their immunosuppression regimen post-transplantation at the time of enrollment and during the trial period
• Participants who have received a multi-organ transplant involving a kidney (e.g. kidney-pancreas, kidney-liver, kidney-heart)
• Participants who are treated or planned to be treated during trial participation with leflunomide, cidofovir, or medicinal products potentially active against BKV at the time of randomization and during the trial period until end of treatment.
• Participants who received antibody-depletion therapy within 3 months prior to randomization, or in the opinion of the Investigator are likely to require antibody-depletion therapy during trial participation. Antibody-depletion therapies include but are not necessarily limited to plasmapheresis, immunoadsorption, and intravenous immunoglobulins (IVIg)
• Participants with active kidney transplant rejection or those considered at high-risk of recurrence of native kidney disease (e.g. primary focal segmental glomerulosclerosis \[FSGS\], C3 glomerulopathy)
• Participants with known donor-specific antibodies (\[DSA\], de novo, or pre-transplantation). Kidney transplant recipients with low-level pretransplant DSAs (<1,000 mean fluorescence intensity \[MFI\]) can be included if no impact on the trial assessments is expected by the discretion of the Investigator.
• Pregnant or nursing (lactating) women
• Uncontrolled acute or chronic infections such as hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV), cytomegalovirus (CMV), or Epstein-Barr virus (EBV)
• 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
• Documented evidence of the use of another Investigational Medicinal Product (IMP) within 30 days or 5 half-lives of randomization, or until the expected PD effect has returned to baseline (whichever is longer)
• Known current alcoholism or drug addiction
• Any other condition or laboratory abnormality, that in the opinion of the Investigator, would interfere with the evaluation of the IMP or interpretation of the participant safety data or trial results.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07503561 · AIC468-01-II/III-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗