NCT06040346

Open-Label Study to Assess Meplazumab in Adult Patients Diagnosed with Plasmodium Falciparum

A Phase 2a, Multicenter, Open-label, Dose-finding, Dose Escalation Study of Meplazumab in Adult Patients Diagnosed with Uncomplicated Plasmodium Falciparum Malaria

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Not accepted

Summary

This phase 2a open-label study to assess Meplazumab in adult patients diagnosed with Plasmodium falciparum

Detailed description

Rationale: Meplazumab, an erythrocytic stage-macromolecular antibody drug, has the potential to control clinical occurrence of falciparum malaria. Meplazumab is a humanized anti-CD147 immunoglobulin G subclass 2 (IgG2) monoclonal antibody with strong affinity to CD147. CD147 is expressed on erythrocyte lineage cells throughout erythroid development, including mature erythrocytes and is the target for Plasmodium merozoites to allow reorientation and subsequent invasion of the erythrocytes. Nonclinical studies have demonstrated that meplazumab binding to CD147 interferes with the receptor-ligand interaction between CD147 and rhoptry-associated protein 2 (RAP2) of the P. falciparum merozoite and inhibits the formation of parasitophorous vacuoles of P. falciparum thus preventing the invasion of P. falciparum into human erythrocytes. Furthermore, the therapeutic and prophylactic effects of meplazumab were demonstrated in vivo using a human erythrocyte chimeric NOG mouse model, which is considered as an optimal choice for in vivo inhibition efficacy study for human-hosted P. falciparum. Meplazumab has previously been studied in healthy participants in two Phase 1 studies and has also been evaluated for activity in 2 completed clinical trials in patients diagnosed with coronavirus disease 2019 (COVID 19). In the safety, tolerability, and pharmacokinetics study in healthy participants, MPZ I-01, results demonstrated a high and prolonged receptor occupancy (RO%) of meplazumab at CD147. This Phase 2a study is designed as a dose escalation trial to assess safety of meplazumab in the target population and to evaluate whether meplazumab is efficacious in treating malaria. The data obtained in this study will be used to determine a recommended meplazumab dose for future Phase 2b and 3 efficacy trials. Overall Design: This is a Phase 2a multicenter, open-label, dose-finding, dose escalation study. The study will recruit participants with confirmed P. falciparum infection. Up to 60 participants will be enrolled into 1 of 3 meplazumab dose levels (20 participants /dose level). Number of Participants: Up to 60 participants will be enrolled into 1 of 3 meplazumab dose levels (20 participants/dose level). Intervention Groups and Duration: Participants will be administered a single intravenous (IV) infusion dose of meplazumab 120±5 minutes on Day 0 and confined for 72 hours after dosing (up to Day 3) to monitor for safety and tolerability of therapy, and to ensure treatment response. During confinement, blood sampling for safety, pharmacokinetic (PK), and RO pharmacodynamic (PD) testing at predefined times will be collected as specified per the Schedule of Assessment (SoA). Furthermore, in a subset of 10 participants/dose level, additional (serial) PK and PD sample will be collected at 1, 2, 4 and 8 hours post end-of-infusion. Up to 3 additional samples may be added to the Day 0-3 serial sample collection period. If clinically well, participants may be discharged from the clinical unit on Day 3 at the Investigator's discretion. Participants will return to the study center for follow-up visits on Days 28±2, 56±7, 84±7 and 182±7 (End of Study) for safety, tolerability, PK, PD (RO rate), and immunogenicity assessments as per the SoA (Weeks 4, 8, 12 and 26).

Conditions

• Malaria

Interventions

Type	Name	Description
DRUG	Meplazumab for Injection	Meplazumab, an erythrocytic stage-macromolecular antibody drug, has the potential to control clinical occurrence of falciparum malaria. Meplazumab is a humanized anti-CD147 immunoglobulin G subclass 2 (IgG2) monoclonal antibody with strong affinity to CD147. CD147 is expressed on erythrocyte lineage cells throughout erythroid development, including mature erythrocytes and is the target for Plasmodium merozoites to allow reorientation and subsequent invasion of the erythrocytes.

Timeline

• Start date: 2024-04-26
• Primary completion: 2025-08-01
• Completion: 2025-10-09
• First posted: 2023-09-15
• Last updated: 2024-10-29

Locations

1 site across 1 country: Kenya