Safety, Tolerability, and Pharmacokinetics and Pharmacodynamics of TB31F

NCT04238689 | Completed Phase 1 Results DMC

• 1 other identifier: NL69779.091.19
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malaria,Falciparum

Keywords

malaria; monoclonal antibody; falciparum; TB31F; transmission blocking; gametocyte

Outcome Measures

Primary Outcomes (1)

• Number and Severity of Adverse Events After TB31F Administration

  * Number and severity of solicited local adverse events of all severities from first product administration through day 7; * Number and severity of solicited general adverse events and clinically significant hematological and biochemical laboratory abnormalities from first product administration through day 28; * Number and severity of unsolicited adverse events from first product administration through end of study; * Occurrence of serious adverse events from first product administration through end of study

  Throughout study: solicited local adverse events (day 0 - day 7); solicited general adverse events and clinically significant laboratory abnormalities (day 0 - day 28); unsolicited adverse events (day 0 - day 84), serious adverse events (day 0 - day 84)

Secondary Outcomes (2)

• Serum Concentration of TB31F

  All groups: 6 hours, 24 hours, 48 hours, day 7, day 14, day 21, day 28, day 56, day 84. Groups 1-4 only: end of infusion, 1 hour, 3 hours. Group 5 only: day 4 and day 10.

• Pharmacodynamics/Functional Transmission-reducing Activity of TB31F

  Groups 1 to 4: throughout study until day 84 (baseline, end of infusion, day 7, day 28, day 56, day 84). Group 5: baseline, day 2, day 4, day 7. day 10, day 14, day 28, day 56, day 84.

Study Arms (5)

Group 1 - 0.1mg/kg TB31F

EXPERIMENTAL

0.1 mg/kg of monoclonal antibody TB31F is administered intravenously to 5 subjects. Subjects will be observed for the occurrence of any adverse events. There will be a minimum of 48 hours between TB31F administration to each subsequent volunteer. Subjects will be followed-up for 84 days. Escalation to the next higher dosage group will be dependent upon no safety signals arising.

Biological: TB31F

Group 2 - 1mg/kg TB31F

EXPERIMENTAL

1 mg/kg of monoclonal antibody TB31F is administered intravenously to 5 subjects. TB31F administration will be staggered such that the first subject will be administered mAb TB31F and observed for the occurrence of any adverse events. The second subject will not receive their dose of TB31F sooner than 2 days after the first subject has received TB31F. The remaining three subjects will receive their TB31F dose no sooner than 2 days after the second subject has been administered TB31F, with at least a one hour interval in administration of TB31F between each subject. Subjects will be followed-up for 84 days. Escalation to the next higher dosage group will be dependent upon no safety signals arising.

Biological: TB31F

Group 3 - 3mg/kg TB31F

EXPERIMENTAL

3 mg/kg of monoclonal antibody TB31F is administered intravenously to 5 subjects. TB31F administration will be staggered such that the first subject will be administered mAb TB31F and observed for the occurrence of any adverse events. The second subject will not receive their dose of TB31F sooner than 2 days after the first subject has received TB31F. The remaining three subjects will receive their TB31F dose no sooner than 2 days after the second subject has been administered TB31F, with at least a one hour interval in administration of TB31F between each subject. Subjects will be followed-up for 84 days. Escalation to the next higher dosage group will be dependent upon no safety signals arising.

Biological: TB31F

Group 4 - 10mg/kg TB31F

EXPERIMENTAL

10 mg/kg of monoclonal antibody TB31F is administered intravenously to 5 subjects. TB31F administration will be staggered such that the first subject will be administered mAb TB31F and observed for the occurrence of any adverse events. The second subject will not receive their dose of TB31F sooner than 2 days after the first subject has received TB31F. The remaining three subjects will receive their TB31F dose no sooner than 2 days after the second subject has been administered TB31F, with at least a one hour interval in administration of TB31F between each subject. Subjects will be followed-up for 84 days.

Biological: TB31F

Group 5 - 100mg TB31F

EXPERIMENTAL

100mg of monoclonal antibody TB31F is administered subcutaneously to 5 subjects. TB31F administration will be staggered such that the first subject will be administered mAb TB31F and observed for the occurrence of any adverse events. The second subject will not receive their dose of TB31F sooner than 2 days after the first subject has received TB31F. The remaining three subjects will receive their TB31F dose no sooner than 2 days after the second subject has been administered TB31F, with at least a one hour interval in administration of TB31F between each subject. Subjects will be followed-up for 84 days.

Biological: TB31F

Interventions

TB31F BIOLOGICAL

Monoclonal antibody

Group 1 - 0.1mg/kg TB31F; Group 2 - 1mg/kg TB31F; Group 3 - 3mg/kg TB31F; Group 4 - 10mg/kg TB31F; Group 5 - 100mg TB31F

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject must sign written informed consent to participate in the trial.
• 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).
• In the opinion of the investigator, the subject can and will comply with the requirements of the protocol.
• 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).
• The subject will remain within reasonable travelling distance from the study center from day -1 until day +7 after mAb TB31F infusion.
• 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.
• 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).
• The subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period according to current Sanquin guidelines.

You may not qualify if:

• 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:
• 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.
• 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.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
• 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.
• Screening tests positive for Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV).
• Use of any investigational or non-registered product (drug or vaccine) during the study period other than the study product.
• Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.
• Prior receipt of an investigational antimalarial monoclonal antibody.
• History of adverse reactions to monoclonal antibodies.
• 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.
• Any history of malaria, positive serology for P. falciparum, or previous participation in any malaria (vaccine) study or Controlled Human Malaria Infection.
• Body weight \>= 115 kg
• 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.
• History of drug or alcohol abuse interfering with normal functioning in the period of one year prior to study onset.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• The PATH Malaria Vaccine Initiative (MVI): collaborator

Study Sites (1)

Radboud University Medical Center

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Related Publications (1)

• van der Boor SC, Smit MJ, van Beek SW, Ramjith J, Teelen K, van de Vegte-Bolmer M, van Gemert GJ, Pickkers P, Wu Y, Locke E, Lee SM, Aponte J, King CR, Birkett AJ, Miura K, Ayorinde MA, Sauerwein RW, Ter Heine R, Ockenhouse CF, Bousema T, Jore MM, McCall MBB. Safety, tolerability, and Plasmodium falciparum transmission-reducing activity of monoclonal antibody TB31F: a single-centre, open-label, first-in-human, dose-escalation, phase 1 trial in healthy malaria-naive adults. Lancet Infect Dis. 2022 Nov;22(11):1596-1605. doi: 10.1016/S1473-3099(22)00428-5. Epub 2022 Aug 10.

  PMID: 35963275 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: Dr. Matthew B.B. McCall
• Organization: Radboudumc, Department of Medical Microbiology

matthew.mccall@radboudumc.nl

+31 024 361 1111

Study Officials

• Matthew BB McCall, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 23, 2019
• First Posted: January 23, 2020
• Study Start: February 14, 2020
• Primary Completion: March 4, 2021
• Study Completion: March 4, 2021
• Last Updated: March 27, 2023
• Results First Posted: March 27, 2023

Record last verified: 2021-01

Locations

NL (1)