A Bioequivalence and Efficacy Study of MB-102 (Relmapirazin) in Chinese Participants

NCT05943977 | Completed Phase 3 FDA Drug FDA Device

• 2 other identifiers: HDNP102-301CTR20230300
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 2

Brief Summary

Part I (bioequivalence) will evaluate the bioequivalence of the Oversea Manufactured Sample (used in the MediBeacon Phase 3 Study 100-103; NCT05425719) and Domestic Manufactured Sample in Single Intravenous Dose of MB-102 (Relmapirazin) in healthy Chinese adults. Part II (efficacy) will evaluate the performance of the MediBeacon Transdermal GFR Measurement System and Domestic Manufactured Sample of MB-102 (Relmapirazin) for Evaluation of Kidney Function in Chinese participants.

Conditions

Kidney Diseases; Kidney Injury; Kidney Failure

Keywords

Glomerular Filtration Rate; Relmapirazin; Pharmacokinetics; MB-102

Outcome Measures

Primary Outcomes (2)

• Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of MB-102

  Blood samples will be collected pre-dose (within 60 minutes prior to dosing) and at 5 min, 15 min, 30 min, 60 min, 90 min (±2 min), 2h, 3h, 4h, 5h, 6h, 8h, 10h , 12h, 16h, 20h and 24h (±5 min) post-dose, and will be analyzed using validated analytical methods. The area under the plasma concentration-time curve (ng\*hr/mL) from time 0 to infinity will be calculated as: AUC0-last+Clast//λz where Clast is the predicted concentration (based on the terminal regression) at the time of the last measurable concentration.

  Pre-dose (within 60 minutes prior to dosing) and at 5 minutes, 15 minutes, 30 minutes, 60 minutes, 90 minutes (±2 minutes), 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 20 hours and 24 hours (±5 minutes) post-dose

• Correlation of transdermal derived glomerular filtration rate (tGFR) to the plasma-derived indexed glomerular filtration rate (nGFR)

  Statistical agreement between tGFR and nGFR will be calculated using P30 statistics

  Up to 24 hours

Secondary Outcomes (9)

• Maximum Plasma Concentration (Cmax) of MB-102

  Pre-dose (within 60 minutes prior to dosing) and at 5 minutes, 15 minutes, 30 minutes, 60 minutes, 90 minutes (±2 minutes), 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 20 hours and 24 hours (±5 minutes) post-dose

• Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration for MB-102 (AUC0-last)

  Pre-dose (within 60 minutes prior to dosing) and at 5 minutes, 15 minutes, 30 minutes, 60 minutes, 90 minutes (±2 minutes), 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 20 hours and 24 hours (±5 minutes) post-dose

• The terminal rate constant (Lambda_z) of MB-102

  Pre-dose (within 60 minutes prior to dosing) and at 5 minutes, 15 minutes, 30 minutes, 60 minutes, 90 minutes (±2 minutes), 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 20 hours and 24 hours (±5 minutes) post-dose

• Total plasma clearance (CL) of MB-102

  Pre-dose (within 60 minutes prior to dosing) and at 5 minutes, 15 minutes, 30 minutes, 60 minutes, 90 minutes (±2 minutes), 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 20 hours and 24 hours (±5 minutes) post-dose

• Volume of distribution (Vd) of MB-102

  Pre-dose (within 60 minutes prior to dosing) and at 5 minutes, 15 minutes, 30 minutes, 60 minutes, 90 minutes (±2 minutes), 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 20 hours and 24 hours (±5 minutes) post-dose

Study Arms (4)

130 mg MB-102 DMID, then 130 mg MB 102-OMID

EXPERIMENTAL

Participants will receive a single 130 mg dose of the MB-102 Domestic Manufactured Investigational Drug (DMID), and blood and urine samples will be collected per protocol. There will be a 5-day washout period between treatments, and then participants will receive a single 130 mg dose of the MB-102 Overseas Manufactured Investigational Drug (OMID). Blood and urine samples will be collected per protocol

Drug: MB-102 DMID; Drug: MB-102 OMID

130 mg MB-102 OMID, then 130 mg MB 102-DMID

EXPERIMENTAL

Participants will receive a single 130 mg dose of the MB-102 Overseas Manufactured Investigational Drug (OMID), and blood and urine samples will be collected per protocol. There will be a 5-day washout period between treatments, and then participants will receive a single 130 mg dose of the MB-102 Domestic Manufactured Investigational Drug (DMID). Blood and urine samples will be collected per protocol.

Drug: MB-102 DMID; Drug: MB-102 OMID

Participants with eGFR ≥ 70 mL/min/1.73 m^2

EXPERIMENTAL

130 mg of the MB-102 Domestic Manufactured Investigational Drug (DMID) will be administered to participants with estimated glomerular filtration rate (eGFR) eGFR ≥ 70 mL/min/1.73 m\^2, and fluorescence measured using the MediBeacon Transdermal GFR Measurement System

Drug: MB-102 DMID; Device: MediBeacon Transdermal Glomerular Filtration Rate Measurement System (TGFR)

Participants with eGFR < 70 mL/min/1.73 m^2

EXPERIMENTAL

130 mg of the MB-102 Domestic Manufactured Investigational Drug (DMID)will be administered to participants with estimated glomerular filtration rate (eGFR) eGFR \< 70 mL/min/1.73 m\^2, and fluorescence measured using the MediBeacon Transdermal GFR Measurement System

Drug: MB-102 DMID; Device: MediBeacon Transdermal Glomerular Filtration Rate Measurement System (TGFR)

Interventions

MB-102 DMID DRUG

130 mg of the MB-102 Domestic Manufactured Investigational Drug administered by intravenous injection over 30-60 seconds, followed by a 10 mL normal saline flush administered over 30-60 seconds.

Also known as: Relmapirazin

130 mg MB-102 DMID, then 130 mg MB 102-OMID; 130 mg MB-102 OMID, then 130 mg MB 102-DMID; Participants with eGFR < 70 mL/min/1.73 m^2; Participants with eGFR ≥ 70 mL/min/1.73 m^2

MB-102 OMID DRUG

130 mg of the MB-102 Overseas Manufactured Investigational Drug (OMID) administered by intravenous injection over 30-60 seconds, followed by a 10 mL normal saline flush administered over 30-60 seconds.

Also known as: Relmapirazin

130 mg MB-102 DMID, then 130 mg MB 102-OMID; 130 mg MB-102 OMID, then 130 mg MB 102-DMID

MediBeacon Transdermal Glomerular Filtration Rate Measurement System (TGFR) DEVICE

On treatment day, participants will have the TGFR sensor placed on their chests, and the MediBeacon Transdermal GFR Measurement System will be initiated to collect background fluorescence. When this is completed, participants will then receive a single dose of MB-102. Fluorescent measurements terminated by the system when a low signal-to-noise threshold is reached.

Participants with eGFR < 70 mL/min/1.73 m^2; Participants with eGFR ≥ 70 mL/min/1.73 m^2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Bioequivalence study:
• The participant is aged 18-55 years, inclusive, at the date of informed consent
• Eligible female non-pregnant participants who are either not of child-bearing potential or willing to use adequate contraception during the trial and at least 1 month post-dose
• Males must be willing to practice abstinence or utilize adequate contraception from dosing day to at least 1 month post-dose
• For women of child-bearing potential, the participant should have a negative serum pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly during the trial and at least 1 month post-dose, i.e. abstinence, oral contraceptive either combined or progesterone alone; injectable progesterone, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, IUD device or system or male partner sterilization
• The participant weighs at least 50 kg, and has a body mass index (BMI) between 19 and 25 kg/m2, inclusive, at Screening
• The participant is a Chinese healthy adult male or female
• Men will not donate sperm during the study and for 1 month following the last dose of study drug
• Participants who are capable of directly providing informed consent and who can comply with the requirements and restrictions required by the protocol
• Adequate venous access sufficient to allow blood sampling per protocol requirements
• Efficacy study:
• Age \> 18 years - male or female
• Eligible female non-pregnant participants who are either not of child-bearing potential or willing to use adequate contraception during the trial and at least 1 month post-dose
• Males must be willing to practice abstinence or utilize adequate contraception from dosing day to at least 1 month post-dose
• For women of child-bearing potential, the participant should have a negative serum pregnancy test at Screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly during the trial and at least 1 month post-dose, i.e. abstinence, oral contraceptive either combined or progesterone alone; injectable progesterone, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, IUD device or system or male partner sterilization

You may not qualify if:

• Bioequivalence study:
• Participants positive via PCR testing for COVID-19
• Recent donation or loss of blood or plasma: 100 mL to 499 mL within 30 days prior to the initial dose of the study medication; or more than 499 mL within 56 days prior to the initial dose of study medication
• Non-steroidal anti-inflammatory (NSAID) use within 3 days of MB-102 dosing.
• The participant has participated in a clinical trial and has received an investigational product within the following time ranges: prior to the first dosing day in the current study: either 30 days or 5 half-lives of the investigational product (whichever duration is longer).
• History of severe allergic hypersensitivity reactions (unacceptable adverse events) or anaphylactoid reaction to any allergen including drugs, MB-102 or other related products (intolerance to a drug is not considered a drug allergy).
• Participants with positive serum pregnancy test
• The participant has an abnormal (clinically significant) electrocardiogram (ECG) at Screening or prior to the study drug administration in Period 1
• The participant has abnormal laboratory values that suggest a clinically significant underlying disease, or subject with the following abnormalities at Screening or prior to the study drug administration in Period 1: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>1.5 x the upper limits of normal (ULN)
• History of drug and/or alcohol abuse within the past year.
• Participants with a creatine kinase (CK) value of greater than the upper limit of normal that is not explainable by exercise and that does not come back to reference range upon retest;
• Any reason which, in the opinion of the Principal Investigator or Medical Sub-Investigator, would prevent the participant from safely participating in the study.
• Efficacy study:
• Participants positive via PCR testing for COVID-19
• Recent donation or loss of blood or plasma: 100 mL to 499 mL within 30 days prior to the initial dose of the study medication; or more than 499 mL within 56 days prior to the initial dose of study medicatio

Sponsors & Collaborators

• Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.: lead
• MediBeacon: collaborator

Study Sites (2)

Suzhou Municipal Hospital

Suzhou, Jiangsu, 215008, China

Location

Affiliated hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221000, China

Location

MeSH Terms

Conditions

Kidney Diseases; Renal Insufficiency

Interventions

relmapirazin

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Yuanyuan Luo

  The Affiliated Hospital of Xuzhou Medical University

  PRINCIPAL INVESTIGATOR

• Dong Sun

  The Affiliated Hospital of Xuzhou Medical University

  PRINCIPAL INVESTIGATOR

• Yanxia Yu

  Suzhou Municipal Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2023
• First Posted: July 13, 2023
• Study Start: March 2, 2023
• Primary Completion: November 30, 2023
• Study Completion: November 30, 2023
• Last Updated: January 2, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)