Assess Safety, Tolerability and Pharmacokinetics of AntiBKV in Healthy Adult Volunteers.

NCT05358106 | Completed Phase 1

• 1 other identifier: MTx-AntiBKV-AU-1.02BKVI
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

BK virus (BKV) is a member of the polyomavirus family with a prevalence of up to 90% in the general population. In immunocompromized individuals, such as kidney transplant recipients (KTRs) who receive immunosuppressant therapy to prevent graft rejection, BKV turns into an opportunistic pathogen. BK viremia has been reported to occur in 10-30% of KTRs. BKV is recognized as a leading cause of impaired graft function and premature transplant loss, and is therefore a serious condition in kidney transplant patients. At present, there are no effective agents specifically against BKV available and thus no standard treatment that can effectively reduce or prevent BKV infection/reactivation after renal transplantation. Therefore, the proposed indication for the AntiBKV neutralizing antibody is the treatment of BK virus infections and prevention of BK virus associated complications in KTRs. This study has been designed to evaluate the safety, tolerability, and pharmacokinetic of ascending doses of AntiBKV, a fully human highly neutralising antibody against BKV, administered as a single or multiple intravenous infusions to healthy adult participants. The data obtained in this study will provide the basis for further clinical development of AntiBKV.

Conditions

BK Virus Nephropathy

Outcome Measures

Primary Outcomes (12)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  To assess the number of participants with treatment related adverse events following a single ascending doses (Part 1) and multiple ascending doses (Part 2) of AntiBKV administered intravenously to healthy adult participants.

  Screening (Day -1) to final visit post-treatment (Day 113) for Part 1 and final visit post-treatment (Day 197) for Part 2.

• Change in blood haematology values

  To evaluate the safety and tolerability of single ascending doses (Part 1) and multiple ascending doses (Part 2) of AntiBKV administered intravenously to healthy adult participants. Haematology data will be summarised for each scheduled visit, including observed values, change from baseline, number of out-of-range values and number of clinically significant values.

  Screening (Day -1) to final visit post-treatment (Day 113) for Part 1 and final visit post-treatment (Day 197) for Part 2.

• Change in blood biochemistry values

  To evaluate the safety and tolerability of single ascending doses (Part 1) and multiple ascending doses (Part 2) of AntiBKV administered intravenously to healthy adult participants. Biochemistry data will be summarised for each scheduled visit, including observed values, change from baseline, number of out-of-range values and number of clinically significant values.

  Screening (Day -1) to final visit post-treatment (Day 113) for Part 1 and final visit post-treatment (Day 197) for Part 2.

• Change in urinalysis values

  To evaluate the safety and tolerability of single ascending doses (Part 1) and multiple ascending doses (Part 2) of AntiBKV administered intravenously to healthy adult participants. Urinalysis data will be summarised for each scheduled visit, including observed values, change from baseline, number of out-of-range values and number of clinically significant values.

  Screening (Day -1) to final visit post-treatment (Day 113) for Part 1 and final visit post-treatment (Day 197) for Part 2.

• Change in blood pressure

  To evaluate the safety and tolerability of single ascending doses (Part 1) and multiple ascending doses (Part 2) of AntiBKV administered intravenously to healthy adult participants. Blood pressure results will be summarized for each scheduled timepoint, including observed values, change from baseline, number of out-of-range values and number of clinically significant values.

  Screening (Day -1) to final visit post-treatment (Day 113) for Part 1 and final visit post-treatment (Day 197) for Part 2.

• Change in heart rate

  To evaluate the safety and tolerability of single ascending doses (Part 1) and multiple ascending doses (Part 2) of AntiBKV administered intravenously to healthy adult participants. Heart rate will be summarized for each scheduled timepoint, including observed values, change from baseline, number of out-of-range values and number of clinically significant values.

  Screening (Day -1) to final visit post-treatment (Day 113) for Part 1 and final visit post-treatment (Day 197) for Part 2.

• Change in respiratory rate

  To evaluate the safety and tolerability of single ascending doses (Part 1) and multiple ascending doses (Part 2) of AntiBKV administered intravenously to healthy adult participants. Respiration rate will be summarized for each scheduled timepoint, including observed values, change from baseline, number of out-of-range values and number of clinically significant values.

  Screening (Day -1) to final visit post-treatment (Day 113) for Part 1 and final visit post-treatment (Day 197) for Part 2.

• Change in body temperature

  To evaluate the safety and tolerability of single ascending doses (Part 1) and multiple ascending doses (Part 2) of AntiBKV administered intravenously to healthy adult participants. Body temperature will be summarized for each scheduled timepoint, including observed values, change from baseline, number of out-of-range values and number of clinically significant values.

  Screening (Day -1) to final visit post-treatment (Day 113) for Part 1 and final visit post-treatment (Day 197) for Part 2.

• Participants with abnormal physical examination findings.

  To evaluate the safety and tolerability of single ascending doses (Part 1) and multiple ascending doses (Part 2) of AntiBKV administered intravenously to healthy adult participants. Abnormal physical examination findings during scheduled physical exams will be listed.

  Screening (Day -1) to final visit post-treatment (Day 113) for Part 1 and final visit post-treatment (Day 197) for Part 2.

• Change in P wave duration in electrocardiogram measurement

  To evaluate the safety and tolerability of single ascending doses (Part 1) and multiple ascending doses (Part 2) of AntiBKV administered intravenously to healthy adult participants. ECG parameters will be descriptively summarized for each scheduled timepoint, including observed values and change from baseline.

  Screening (Day -1) to final visit post-treatment (Day 113) for Part 1 and final visit post-treatment (Day 197) for Part 2.

• Change in PR interval in electrocardiogram measurement

  To evaluate the safety and tolerability of single ascending doses (Part 1) and multiple ascending doses (Part 2) of AntiBKV administered intravenously to healthy adult participants. ECG parameters will be descriptively summarized for each scheduled timepoint, including observed values and change from baseline.

  Screening (Day -1) to final visit post-treatment (Day 113) for Part 1 and final visit post-treatment (Day 197) for Part 2.

• Change in QRS duration in electrocardiogram measurement

  To evaluate the safety and tolerability of single ascending doses (Part 1) and multiple ascending doses (Part 2) of AntiBKV administered intravenously to healthy adult participants. ECG parameters will be descriptively summarized for each scheduled timepoint, including observed values and change from baseline.

  Screening (Day -1) to final visit post-treatment (Day 113) for Part 1 and final visit post-treatment (Day 197) for Part 2.

Secondary Outcomes (6)

• Pharmacokinetics measured by the maximum plasma concentration (Cmax)

  Treatment Day 1 to final visit (Day 113) for Part 1 and final visit (Day 197) for Part 2.

• Pharmacokinetics measured by the time of Cmax (Tmax)

  Treatment Day 1 to final visit (Day 113) for Part 1 and final visit (Day 197) for Part 2.

• Pharmacokinetics measured by the area under the curve (AUC)

  Treatment Day 1 to final visit (Day 113) for Part 1 and final visit (Day 197) for Part 2.

• Pharmacokinetics measured by the terminal elimination rate constant (λz)

  Treatment Day 1 to final visit (Day 113) for Part 1 and final visit (Day 197) for Part 2.

• Pharmacokinetics measured by the half life

  Treatment Day 1 to final visit (Day 113) for Part 1 and final visit (Day 197) for Part 2.

Study Arms (2)

AntiBKV neutralising antibody

ACTIVE COMPARATOR

AntiBKV infused i.v. over 30 minutes. Infusion parameters may be adjusted to bodyweight so that infusion rate does not exceed 60mg/kg per hour. AntiBKV will be administered as a single infusion in Part 1 or as 4 infusions administered 4 weeks apart in Part 2 (100, 500, 1000 or 2000 mg).

Biological: AntiBKV

Placebo

PLACEBO COMPARATOR

Solution containing no active excipients, infused i.v. over 30 minutes as a single infusion in Part 1 or as 4 infusions administered 4 weeks apart in Part 2.

Biological: Placebo

Interventions

AntiBKV BIOLOGICAL

AntiBKV neutralising antibody

AntiBKV neutralising antibody

Placebo BIOLOGICAL

Solution with no active ingredients

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female participants aged 18 years to 50 years at the time of consent
• Ability to read, understand and provide written informed consent
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including lifestyle restrictions for the duration of the study
• Healthy participants as established by medical history, laboratory examination, physical examination, vital signs, and ECG during screening and as per the clinical judgment of the investigator
• Body mass index (BMI) of 18.0 to 32.0 kg/m2 (inclusive)
• For Woman of Childbearing Potential (WOCBP): agrees to practice true abstinence or agrees to use a highly effective method of contraception consistently from 30 days prior to Day 1 until at least 30 days post-dose. Highly effective contraception includes hormonal contraception, placement of intrauterine device (IUD) or intrauterine system (IUS), or a vasectomized partner (performed at least 6 months prior to her screening) who has been documented to no longer produce sperm. Verbal confirmation from the participant through medical interview is acceptable. No contraception requirements for participants in exclusive same-sex relationship.
• For male participant: must agree to practice true abstinence or use condom if he has a partner of childbearing potential or must be surgically sterilized (performed at least 6 months prior and documented to no longer produce sperm. Verbal confirmation through medical interview is acceptable). Participant to practice abstinence (if applicable) or use condom for at least 30 days post-dose. No contraception requirements for participants in exclusive same-sex relationship.
• Accessible veins in the forearms for venepuncture and/or intravenous cannulation

You may not qualify if:

• Participant with active SARS-CoV-2 infection
• Participants tested positive for human immunodeficiency virus (HIV antibody screen), Hepatitis B virus (HBsAg screen) or Hepatitis C virus (HCV antibody screen)
• History of administration of any investigational or non-registered drug within 30 days or 5 half-lives, whichever is longer, prior to administration of study drug, or planned administration during the course of study participation.
• History of any reaction to monoclonal antibodies.
• History of allergic disease or reactions likely to be exacerbated by any component of the study drug, as assessed by the investigator, and/or known allergies to the trial product or its components.
• Acute illness (moderate or severe) and/or fever (body temperature ≥ 38 °C) during the 72 hours prior to any planned study drug application.
• Participants with altered immunocompetence such as participants with ongoing cancer treatment, human immunodeficiency virus infection, organ transplant or any other active immune system disorder. Participants with seasonal allergies and mild asthma may be included.
• Receipt of immunoglobulin or blood products within 6 months prior to enrolment.
• Receipt of a monoclonal antibody within previous 6 months or 5 half-lives, whichever is longer.
• Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the course of the study.
• Receipt, or planned receipt of any standard vaccine within 7 days prior to and 7 days post Day 1 or planned vaccination within 7 days prior to and post any subsequent dosings.
• History of alcoholism (\>10 drinks/week) or drug addiction within 1 year prior to screening.
• Positive screen for drugs of abuse or alcohol (breath test) at screening or Day -1 and prior to any subsequent dosings. A test may be repeated once at the discretion of the investigator to confirm suspected false-positive results.
• Use of prescription drugs within 7 days prior to Day 1 or for 5 half-lives whichever is longer, or during the study, except for hormonal contraceptives.
• Use of over-the-counter medication within 7 days prior to Day 1 or during the study; medication such as paracetamol and ibuprofen may be permitted at the discretion of the investigator and sponsor.

Sponsors & Collaborators

• Memo Therapeutics AG: lead

Study Sites (1)

CMAX Clinical Research Pty Ltd

Adelaide, South Australia, 5000, Australia

Location

Related Publications (1)

• Helle F, Aubry A, Morel V, Descamps V, Demey B, Brochot E. Neutralizing Antibodies Targeting BK Polyomavirus: Clinical Importance and Therapeutic Potential for Kidney Transplant Recipients. J Am Soc Nephrol. 2024 Oct 1;35(10):1425-1433. doi: 10.1681/ASN.0000000000000457. Epub 2024 Jul 9.

  PMID: 39352862 DERIVED

Study Officials

• Jürgen Beck

  Memo Therapeutics AG

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Single-blind study where participants are blinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single-blind, partially randomized, placebo-controlled study in healthy volunteers. Approximately 40 to 56 healthy adult participants are planned to be enrolled in 7 cohorts of 4 to 8 participants, randomized in a 3:1 ratio to receive AntiBKV or placebo

Study Record Dates

• First Submitted: March 23, 2022
• First Posted: May 3, 2022
• Study Start: May 9, 2022
• Primary Completion: December 5, 2022
• Study Completion: April 2, 2023
• Last Updated: June 18, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)