Malaria
Conditions
Interventions
Meplazumab
Sponsors
Jiangsu Pacific Meinuoke Biopharmaceutical Co. Ltd. PMBP
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: . Ability to provide informed consent signed by the study participant or legally authorized representative 2. Adults 18 to 55 years at the time of signing the informed consent form (ICF) 3. Female participants are eligible to participate if they do not qualify as a woman of childbearing potential (WOCBP), as defined in Section 10.4. 4. Male participants who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Section 10.4. 5. BMI =18 to =30 kg/m2 6. Mono-infection with P. falciparum documented by: • Microscopically confirmed parasite infection using Giemsa-stained thick film (refer to the laboratory manual for details) consisting of 1000 – 100,000 asexual parasites /µL of blood and • Documented fever (=38.0°C oral, rectal or tympanic; =37.5°C axillary) or documented history of fever in previous 24 hours
Exclusion criteria
Exclusion criteria: Presence of severe malaria (as defined by World Health Organization Guidelines for Malaria 16 February 2021). • Severe falciparum malaria is defined as one or more of the following, occurring in the absence of an identified alternative cause and in the presence of P. falciparum asexual parasitemia. o Impaired consciousness: A Glasgow coma score 8 mEq/L or, if not available, a plasma bicarbonate level of 10,000/µL o Renal impairment: Plasma or serum creatinine >265 µmol/L (3 mg/dL) or blood urea >20 mmol/L o Jaundice: Plasma or serum bilirubin >50 µmol/L (3 mg/dL) with a parasite count >100,000/ µL o Pulmonary edema: Radiologically confirmed or oxygen saturation 30/min, often with chest indrawing and crepitations on auscultation o Significant bleeding: Including recurrent or prolonged bleeding from the nose, gums or venepuncture sites; hematemesis or melena o Shock: Compensated shock is defined as capillary refill =3 s or temperature gradient on leg (mid to proximal limb), but no hypotension. Decompensated shock is defined as systolic blood pressure 10% 2. Antimalarial treatment (alone or in combination) during the following periods before Screening: • Piperaquine, mefloquine, naphthoquine or sulfadoxine-pyrimethamine within 6 weeks prior to Screening. • Amodiaquine, chloroquine within 4 weeks prior to Screening. • Any artemisinin derivative (artesunate, artemether or dihydroartemisinin), quinine, lumefantrine or any other antimalarial treatment or antibiotic with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones and azithromycin) within 14 days prior to Screening. • Any herbal products or traditional medicines, within the past 7 days. 3. Previous participation in any malaria vaccine study or received malaria vaccine within 3 months of Screening Visit. 4. Known allergy to any study medication, including allergy to any component of protocol prescribed rescue treatment i.e., country-specific ACT regimen. CONFIDENTIAL Protocol MPZ-MAL-01 [Amendment 1] 35 of 78 5. Any clinically important illness as judged by the investigator, including but not limited to a history of clinically significant chronic respiratory disease (eg, chronic obstructive pulmonary disease [COPD] or asthma), medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational product. 6. Participants participate in another clinical study. There will be a need for washout with 5 half-lives depending on the study treatment or 30 days, whichever is longer. 7. Use of anti-cancer, anti-transplant rejection, or immunomodulatory biological drug or kinase inhi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of AE • Incidence of (number of participants with): o Drug-related SAE o All-cause SAE o Drug-related AESI o All-cause AESI o Participants discontinuation/ withdrawals due to AE | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary • To evaluate the efficacy of meplazumab as defined by: o Early treatment failure o Late clinical failure o Late parasitological failure o Uncorrected ACPR • Incidence (number of participants with) of early treatment failure • Incidence of late clinical failure • Incidence of late parasitological failure • Incidence of uncorrected ACPR at Day 28 • To evaluate PRR • PRR at 72h • To determine the recrudescence (see Section 9.3.7) and re-infection (see Section 9.3.7) • Incidence of (number of participants with) recrudescence and re-infection at Week 4 • Time to recrudescence and re-infection at Week 4 • To determine the time to relief of fever • FCT at 72h • To determine the dose-response trend relationship between 3 dose levels of meplazumab by evaluation of safety, efficacy and ACPR outcomes • Dose-response trend relationship between the 3 dose levels of meplazumab, based on change from baseline in the summary of the safety and efficacy outcomes to Week 4 • To evaluate the pharmacokinetics of meplazumab in serum • Meplazumab serum concentration-time profiles and PK parameters including but not limited to Cmax, tmax, AUC(0-last), AUC(0-inf), t½, CL, Vz, and Vss • To evaluate immunogenicity following meplazumab administration • Frequency of confirmed anti-drug antibody (ADA) response, ADA titers, and neutralizing activity Exploratory • To evaluate the efficacy of meplazumab by PCR-corrected ACPR • Incidence of (number of participants with) PCR-corrected ACPR at Week 4 • To evaluate RO (%) of meplazumab in red blood cells following single dose administration • Meplazumab RO%-time profiles, pharmacodynamic parameters determined for RO including but not limited to maximum RO% and duration RO% (RO% half-life | — |
Countries
Gabon, Ghana, Kenya, Rwanda
Contacts
Public ContactMichelle Botha
Assoc DirectorGlobal Site Activation
Outcome results
None listed