Efficacy of SJ733 in Adults With Uncomplicated Plasmodium Falciparum or Vivax Malaria
Condition: Malaria, Falciparum; Malaria, Vivax
MeSH terms: Malaria; Malaria, Falciparum; Malaria, Vivax
Intervention: (+)-SJ000557733 (SJ733)
Intervention description: Anti-Malarial
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: There are 6 treatment arms (three cohorts, each with P. falciparum and P.vivax arms).Cohort progression will be managed independently for each treatment arm. Interim analysis will determine whether the data for each arm meets the success criteria
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This Phase 2a trial recruits adult patients with uncomplicated P. vivax or P. falciparum
      blood-stage malaria mono-infection. The study drug SJ733 will be administered to examine its
      antimalarial efficacy, safety, and tolerability. This study also evaluates whether or not a
      fixed dose of the pharmacoenhancer cobicistat when given in combination with SJ733
      significantly improves drug efficacy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female, aged 18 to 70 years of age (inclusive) at screening.

          2. Body weight between 45 kg and 90 kg inclusive

          3. Presence of mono-infection of P. falciparum or P. vivax confirmed by:

               1. Fever, as defined by axillary temperature ≥ 37.5°C or oral/rectal/tympanic
                  temperature ≥ 38°C, or history of fever in the previous 24 hours (history of
                  fever must be documented) and,

               2. Microscopically confirmed parasite infection: 1,000 to 40,000 asexual parasite
                  count/µL blood

          4. Written informed consent provided by participant, in accordance with local practice.
             If the participant is unable to write, witnessed consent is permitted according to
             local ethical considerations.

          5. Ability to swallow oral medication.

          6. Ability and willingness to participate and to comply with the study requirements

          7. Agreement to hospitalization for at least 102 hours and/or until malarial parasites
             are not detected by microscopy on 2 consecutive occasions.

          8. Agreement to come back to the hospital on Days 7, 10 or 11, 14, 17 or 18, 21, 24 or
             25, 28, 35, and 42.

          9. Women of child-bearing potential, has a negative pregnancy test at screening, and
             agrees to comply with one of the following during the treatment stage of the study and
             for a period of 90 days after stopping study drug:

               1. Use of oral, implantable, or injectable hormonal contraceptive, either combined
                  or progestogen alone used in conjunction with barrier method as defined below.

               2. Use of an intrauterine device with a documented failure rate of <1% per year.

               3. Barrier method consisting of either condom or diaphragm.

               4. Male partner who is sterile prior to the female subject's entry into the study
                  and is the sole sexual partner for that female.

               5. Complete abstinence from intercourse for 2 weeks prior to administration of study
                  drug, throughout the study and for a period of 90 days after stopping study drug.

        Exclusion Criteria:

          1. Signs and symptoms of severe/complicated malaria according to the World Health
             Organization Criteria 2010 (Attachment 1: Definition of Severe Malaria)

          2. Mixed Plasmodium infection.

          3. Severe vomiting, defined as more than three times in the 24 hours prior to inclusion
             in the study, or severe diarrhea defined as 3 or more watery stools per day.

          4. Severe malnutrition (defined as the weight-for-height being below -3 standard
             deviation or less than 70% of median of the NCHS/WHO normalized reference values)

          5. Presence of a significant medical or psychiatric condition, or any other serious or
             chronic clinical condition requiring hospitalization, or any other condition that in
             the opinion of the investigator precludes participation in the study.

          6. Female patients must not be either lactating or pregnant as demonstrated by a negative
             serum point-of-care pregnancy test pre-dose (the result of the pre-dose assessment
             must be confirmed negative prior to dosing).

          7. Employment under the direct supervision of the investigators or study staff.

          8. Clinically significant alterations to hematologic or clinical chemistry parameters
             that in the opinion of the investigator precludes participation in the study,
             including:

               1. AST/ALT > 3 x upper limit of normal range (ULN) and total bilirubin is normal

               2. AST/ALT > 2 x ULN and total bilirubin is >1 and <1.5 x ULN and conjugated
                  bilirubin is > 35% of the total bilirubin

               3. Total bilirubin > 1.5 x ULN

               4. Serum creatinine levels > 2 x ULN

               5. Hb level < 8 g/dL

               6. Platelet level < 50,000/mm3

          9. Participation in a clinical study of another investigational small molecule within 30
             days or investigational biologic within 90 days prior to study enrollment or planning
             to begin such participation during the study.

         10. Have received any antimalarial treatment (alone or in combination) in the past
             containing:

               1. Piperaquine, mefloquine, naphthoquine or sulphadoxine / pyrimethamine within the
                  previous 6 weeks

               2. Amodiaquine or chloroquine within the previous 4 weeks

               3. Any artemisinin (artesunate, artemether, arteether or dihydroartemisinin)
                  quinine, halofantrine, lumefantrine and any other anti-malarial treatment or
                  antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines,
                  quinolones and fluoroquinolones, and azithromycin) within the past 14 days

         11. Any medication from the list of prohibited medications.