Malaria (Plasmodium Falciparum) Clinical Trial
Official title:
A Phase 1, 3 Part, Randomized, Placebo Controlled, Ascending Dose Study to Assess Safety, Tolerability, and Pharmacokinetics of Single Intravenous Doses of Meplazumab and to Assess Its Antimalarial Activity Against Plasmodium Falciparum in a Malaria Challenge Model in Healthy Subjects
This Phase 1 study will be conducted to explore the dose regimen in humans and to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and toxicological effects of meplazumab in healthy subjects, thus providing a new macromolecule antibody drug for the prevention and treatment of P. falciparum infection.
2.1 Study Rationale. This Phase 1 study will be conducted to explore the dose regimen in humans and to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and toxicological effects of meplazumab in healthy subjects, thus providing a new macromolecule antibody drug for the prevention and treatment of P. falciparum infection. 2.2 Background. Malaria is a mosquito borne infectious disease that manifests as acute fever. Malaria is caused by Plasmodium spp., a parasite which is transmitted to humans by the bite of an infected female Anopheles mosquito (malaria vector).1 When the infected mosquito bites a human, Plasmodium sporozoites in the mosquito's saliva enter the bloodstream and migrate to the liver where they reproduce within hepatocytes. This stage is known as the exoerythrocytic phase.2 Multiplying merozoites reproduce to form schizonts, which contain several thousand merozoites. Mature schizonts rupture to release merozoites into the blood where they invade erythrocytes,3 hence initiating the merozoites reproduction in the erythrocytic phase.2 Malaria may develop into severe or even fatal disease if not treated in time. Five species of Plasmodium infect humans, including Plasmodium falciparum (P. falciparum), P. vivax, P. ovale, P. malariae, and P. knowlesi.4 Among these, P. falciparum and P. vivax are the most common species, with the former as the most dangerous one which has a high morbidity and may result in rapid progression and high mortality. Current methods toward malaria elimination usually involve the combination of prevention and treatment. Early diagnosis and treatment can mitigate disease progression and reduce deaths. Artemisinin based combination therapies are currently recommended by the World Health Organization for treatment of malaria. Antimalarial drugs mainly include drugs to eliminate Plasmodium during the erythrocytic phase or during the exoerythrocytic phase. From the 1950s, falciparum malaria has progressively developed resistance to all antimalarials marketed including chloroquine, sulfadoxine pyrimethamine, etc leading to ineffective malaria control. Plasmodium spp. Have recently developed resistance to the current frontline drugs, artemisinin combination therapy. Therefore, new antimalarial therapies and drugs are urgently needed to combat drug resistance of Plasmodium. 2.2.1 Meplazumab, a Humanized Anti-CD147 IgG2 Monoclonal Antibody Meplazumab (Ketantin®) is a lyophilized powder for injection of small volume. The main active ingredient of the product, meplazumab, is a humanized immunoglobulin (Ig) G2 monoclonal antibody, consisting of the complementary-determining regions of anti CD147 murine antibody and the human framework region. It acts as an erythrocytic stage-macromolecular antibody drug that has the potential to mediate both treatment and prophylaxis of falciparum malaria. 2.2.2 Preclinical Data Preclinical studies and pharmacological studies have indicated that meplazumab for intravenous (IV) injection is safe and effective with well controlled quality. The nonclinical studies of meplazumab include pharmacology, PD, PK, and toxicology studies. Refer to Section 4 of the current IB for meplazumab for further details. ;