Safety, Tolerability, and Pharmacokinetics and Pharmacodynamics of TB31F
Condition: Malaria,Falciparum
MeSH terms: Malaria; Malaria, Falciparum
Intervention: TB31F
Intervention description: Monoclonal antibody
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Five groups will receive a single dose of mAb TB31F administered intravenously (groups 1-4) or subcutaneously (group 5). Group 1 (n=5) will receive 0.1 mg/kg TB31F, group 2 (n=5) will receive 1 mg/kg TB31F, group 3 (n=5) will receive 3 mg/kg TB31F, group 4 (n=5) will receive 10 mg/kg mAb TB31F, and group 5 will receive 100mg TB31F. Twenty-five (n=25) subjects will be enrolled.
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 35 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: malaria; monoclonal antibody; falciparum; TB31F; transmission blocking; gametocyte

Summary:

      This phase 1 study aims to assess the safety and tolerability of monoclonal antibody TB31F
      administered intravenously or subcutaneously at escalating dose levels in healthy, malaria
      naïve, adults. This study will also evaluate the pharmacokinetics of TB31F and the functional
      activity of mAb TB31F in the standard membrane feeding assay.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject must sign written informed consent to participate in the trial.

          2. Subject is able to understand planned study procedures and demonstrate comprehension
             of the protocol procedures and knowledge of study by passing a quiz (assessment of
             understanding).

          3. In the opinion of the investigator, the subject can and will comply with the
             requirements of the protocol.

          4. Subjects are available to attend all study visits and are reachable by phone
             throughout the entire study period from day -1 until day 84 (end of study).

          5. The subject will remain within reasonable travelling distance from the study center
             from day -1 until day +7 after mAb TB31F infusion.

          6. Subject is a male or non-pregnant and non-lactating female age ≥ 18 and ≤ 35 years and
             in good health at time of mAb infusion.

          7. Subject agrees to their general practitioner (GP) being informed about participation
             in the study and agrees to sign a form to request the release by their GP, and medical
             specialist when necessary, of any relevant medical information concerning possible
             contra-indications for participation in the study to the investigator(s).

          8. The subject agrees to refrain from blood donation to Sanquin or for other purposes
             throughout the study period according to current Sanquin guidelines.

          9. Female subjects of non-childbearing potential may be enrolled in the study.
             Non-childbearing potential is defined as pre-menarche, current bilateral tubal
             ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. All
             subjects must agree to use continuous adequate contraception until 2 months after
             completion of the study. Female subjects must agree not to breastfeed from 30 days
             prior to mAb infusion until 2 months after completion of the study. Female subject
             must have a negative pregnancy test at the inclusion visit.

        Exclusion Criteria:

          1. Acute or chronic disease at time of TB31F administration, clinically significant
             pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by
             physical examination or laboratory screening tests:

               1. Acute disease is defined as the presence of a moderate or severe illness with or
                  without fever. Subjects with a minor illness on the day of TB31F administration
                  will be (temporarily) excluded from participation, but may be re-evaluated for
                  inclusion at a later date. Subjects with a positive SARS-CoV2 test at inclusion
                  will be (temporarily) excluded from participation but may be re-evaluated for
                  inclusion at a later date (following current Radboudumc guidelines).

               2. Fever is defined as an oral, axillary or tympanic temperature ≥ 38.0°C (100.4°F).
                  The preferred route for recording temperature in this study will be oral.

               3. Any abnormal and clinically significant baseline laboratory screening tests of
                  alanine aminotransferase, aspartate aminotransferase, creatinine, hemoglobin,
                  platelet count or total white blood cell count, as defined in the protocol
                  according to the FDA Toxicity Grading Scale for Healthy Adult and Adolescent
                  Subjects Enrolled in Preventative Vaccine Clinical Trials.

          2. History of malignancy of any organ system (other than localized basal cell carcinoma
             of the skin), treated or untreated, within the past 5 years.

          3. Chronic use of i) immunosuppressive drugs, iii) or other immune modifying drugs within
             three months prior to study onset (inhaled and topical corticosteroids and oral
             anti-histamines exempted) or expected use of such during the study period.

          4. Positive urine toxicology test for cannabis, cocaine or amphetamines at screening or
             at inclusion.

          5. Screening tests positive for Human Immunodeficiency Virus (HIV), active Hepatitis B
             Virus (HBV), Hepatitis C Virus (HCV).

          6. Use of any investigational or non-registered product (drug or vaccine) during the
             study period other than the study product.

          7. Participation in any other clinical study in the 30 days prior to the start of the
             study or during the study period.

          8. Prior receipt of an investigational antimalarial monoclonal antibody.

          9. History of adverse reactions to monoclonal antibodies.

         10. Administration of immunoglobulin and/or any blood products within the three months
             preceding the first dose of study mAb or planned administration during the study
             period.

         11. Any history of malaria, positive serology for P. falciparum, or previous participation
             in any malaria (vaccine) study or Controlled Human Malaria Infection.

         12. Body weight >= 115 kg

         13. Being an employee or student of the department of Medical Microbiology or Medium Care
             of the Radboudumc, or a person otherwise related to the investigator other than a
             professional relationship for clinical trial purpose only.

         14. History of drug or alcohol abuse interfering with normal functioning in the period of
             one year prior to study onset.

         15. Any other condition or situation that would, in the opinion of the investigator, place
             the subject at an unacceptable risk of injury or render the subject unable to meet the
             requirements of the protocol.