| . 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 |
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 <11 in adults
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o Prostration: Generalized weakness so that the person is unable to sit, stand or walk
without assistance
o Multiple convulsions: More than 2 episodes within 24 h
o Acidosis: A base deficit of >8 mEq/L or, if not available, a plasma bicarbonate
level of <15 mmol/L or venous plasma lactate ≥5 mmol/L. Severe acidosis
manifests clinically as respiratory distress (rapid, deep, labored breathing).
o Hypoglycemia: Blood or plasma glucose <2.2 mmol/L (<40 mg/dL)
o Severe malarial anemia: Hemoglobin concentration ≤7 g/dL or a hematocrit of ≤20%
in adults with a parasite count >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 <92% on room
air with a respiratory rate >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 <80 mmHg in adults, with evidence of
impaired perfusion (cool peripheries or prolonged capillary refill).
o Hyperparasitemia: P. falciparum parasitemia >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.
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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 inhibitor (e.g., tocilizumab, sarilumab) or Janus kinase inhibitors (within 30 days of
enrollment or 5 times the half-life [whichever is longer]).
8. Systemic administration of corticosteroids (PO/IV/IM) at a dose of ≥20 mg/day of
prednisone or equivalent for more than 14 consecutive days within 90 days prior to
informed consent. Topical, inhaled, and intranasal corticosteroids are permitted.
Intermittent use (one dose in 30 days) of intra-articular corticosteroids are also permitted.
9. Live (live-attenuated) vaccines are not permitted within 2 weeks prior to study treatment
or during the study treatment and safety follow-up periods.
10. Presence of Hepatitis A IgM, Hepatitis B surface antigen, or Hepatitis C antibody, or AntiHIV1 and/or HIV2 antibody , or Rapid Plasma Reagin test positive for syphilis..
11. TBL >1.5 × ULN, ALT >2 × ULN, or AST >2 × ULN.
12. Hematocrit <20%, hemoglobin <70 g/L (<7 g/dL), or white blood count >15,000/μL.
13. Creatinine >1.5 × ULN.
|
Adult: 19 Year-44 Year |
18 Year(s) |
55 Year(s) |
Both |