Ignite Creation Date:
2024-05-06 @ 7:33 PM
Last Modification Date:
2024-10-26 @ 3:08 PM
Study NCT ID:
NCT06040346
Status:
RECRUITING
Last Update Posted:
2024-05-22
First Post:
2023-09-08
Brief Title:
Open-Label Study to Assess Meplazumab in Adult Patients Diagnosed With Plasmodium Falciparum
Sponsor:
Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
Organization:
Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
Study Overview
Official Title:
A Phase 2a Multicenter Open-label Dose-finding Dose Escalation Study of Meplazumab in Adult Patients Diagnosed With Uncomplicated Plasmodium Falciparum Malaria
Status:
RECRUITING
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 participantsdose level
Intervention Groups and Duration
Participants will be administered a single intravenous IV infusion dose of meplazumab 1205 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 participantsdose 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 Investigators discretion Participants will return to the study center for follow-up visits on Days 282 567 847 and 1827 End of Study for safety tolerability PK PD RO rate and immunogenicity assessments as per the SoA Weeks 4 8 12 and 26
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 participantsdose level
Intervention Groups and Duration
Participants will be administered a single intravenous IV infusion dose of meplazumab 1205 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 participantsdose 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 Investigators discretion Participants will return to the study center for follow-up visits on Days 282 567 847 and 1827 End of Study for safety tolerability PK PD RO rate and immunogenicity assessments as per the SoA Weeks 4 8 12 and 26
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None