Trial Outcomes & Findings for Safety, Tolerability, and Pharmacokinetics and Pharmacodynamics of TB31F (NCT NCT04238689)

Last Updated: 2023-03-27

Results Overview

* 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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

25 participants

Primary outcome timeframe

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)

Results posted on

2023-03-27

Participant Flow

Recruitment period: 23 January 2020 - 8 December 2020 Recruitment location: Radboudumc Technology Center Clinical Studies

Participant milestones

Participant milestones
Measure	Group 1 - 0,1mg/kg TB31F 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. TB31F: Monoclonal antibody	Group 2 - 1mg/kg TB31F 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. TB31F: Monoclonal antibody	Group 3 - 3mg/kg TB31F 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. TB31F: Monoclonal antibody	Group 4 - 10mg/kg TB31F 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. TB31F: Monoclonal antibody	Group 5 - 100mg TB31F 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. TB31F: Monoclonal antibody
Overall Study STARTED	5	5	5	5	5
Overall Study COMPLETED	5	5	5	5	5
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety, Tolerability, and Pharmacokinetics and Pharmacodynamics of TB31F

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1 - 0,1mg/kg TB31F n=5 Participants 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. TB31F: Monoclonal antibody	Group 2 - 1mg/kg TB31F n=5 Participants 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. TB31F: Monoclonal antibody	Group 3 - 3mg/kg TB31F n=5 Participants 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. TB31F: Monoclonal antibody	Group 4 - 10mg/kg TB31F n=5 Participants 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. TB31F: Monoclonal antibody	Group 5 - 100mg TB31F n=5 Participants 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. TB31F: Monoclonal antibody	Total n=25 Participants Total of all reporting groups
Age, Continuous	22.0 years n=5 Participants	24.8 years n=7 Participants	26.8 years n=5 Participants	21.6 years n=4 Participants	22.2 years n=21 Participants	23.5 years n=10 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	1 Participants n=21 Participants	13 Participants n=10 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants	12 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	5 Participants n=21 Participants	22 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Weight	73.6 kilograms n=5 Participants	75.5 kilograms n=7 Participants	72.0 kilograms n=5 Participants	71.5 kilograms n=4 Participants	78.4 kilograms n=21 Participants	74.2 kilograms n=10 Participants
Body Mass Index	24.3 kg/m^2 n=5 Participants	25.0 kg/m^2 n=7 Participants	23.4 kg/m^2 n=5 Participants	23.9 kg/m^2 n=4 Participants	23.9 kg/m^2 n=21 Participants	24.1 kg/m^2 n=10 Participants

PRIMARY outcome

Timeframe: 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)

Population: Number of volunteers that experienced a grade 1, 2 or 3 local solicited, general solicited, unsolicited or laboratory adverse event per group.

Outcome measures

Outcome measures
Measure	Group 1 - 0,1mg/kg TB31F n=5 Participants 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. TB31F: Monoclonal antibody	Group 2 - 1mg/kg TB31F n=5 Participants 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. TB31F: Monoclonal antibody	Group 3 - 3mg/kg TB31F n=5 Participants 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. TB31F: Monoclonal antibody	Group 4 - 10mg/kg TB31F n=5 Participants 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. TB31F: Monoclonal antibody	Group 5 - 100mg TB31F n=5 Participants 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. TB31F: Monoclonal antibody
Number and Severity of Adverse Events After TB31F Administration Local Solicited Adverse Events: grade 1	0 Participants	1 Participants	1 Participants	0 Participants	4 Participants
Number and Severity of Adverse Events After TB31F Administration Local Solicited Adverse Events: grade 2	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Adverse Events After TB31F Administration Local Solicited Adverse Events: grade 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Adverse Events After TB31F Administration General Solicited Adverse Events: grade 1	4 Participants	3 Participants	1 Participants	5 Participants	2 Participants
Number and Severity of Adverse Events After TB31F Administration General Solicited Adverse Events: grade 2	3 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number and Severity of Adverse Events After TB31F Administration General Solicited Adverse Events: grade 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Adverse Events After TB31F Administration Unsolicited Solicited Adverse Events: grade 1	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Number and Severity of Adverse Events After TB31F Administration Unsolicited Solicited Adverse Events: grade 2	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Adverse Events After TB31F Administration Unsolicited Solicited Adverse Events: grade 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Adverse Events After TB31F Administration Laboratory Adverse Events grade 1	1 Participants	1 Participants	0 Participants	0 Participants	2 Participants
Number and Severity of Adverse Events After TB31F Administration Laboratory Adverse Events grade 2	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Adverse Events After TB31F Administration Laboratory Adverse Events grade 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Adverse Events After TB31F Administration Laboratory Adverse Events where grade N/A, per protocol	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Adverse Events After TB31F Administration Serious Adverse Event (SAE)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Population: Day 4 and day 10 were not measured for participants in groups 1 to 4, per protocol. Day 56 was not measured for group 1 participants due to COVID-19 pandemic-related restrictions.

The serum concentration of TB31F will be measured in all subjects throughout the study (until day 84) by Pfs48/45 antigen ELISA.

Outcome measures

Outcome measures
Measure	Group 1 - 0,1mg/kg TB31F n=5 Participants 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. TB31F: Monoclonal antibody	Group 2 - 1mg/kg TB31F n=5 Participants 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. TB31F: Monoclonal antibody	Group 3 - 3mg/kg TB31F n=5 Participants 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. TB31F: Monoclonal antibody	Group 4 - 10mg/kg TB31F n=5 Participants 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. TB31F: Monoclonal antibody	Group 5 - 100mg TB31F n=4 Participants 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. TB31F: Monoclonal antibody
Serum Concentration of TB31F End of Infusion	2.59 ug/mL Standard Deviation 0.47	21.03 ug/mL Standard Deviation 3.34	79.54 ug/mL Standard Deviation 15.09	253.91 ug/mL Standard Deviation 51.27	—
Serum Concentration of TB31F 1 hour	2.80 ug/mL Standard Deviation 0.26	29.75 ug/mL Standard Deviation 11.11	69.77 ug/mL Standard Deviation 17.34	237.85 ug/mL Standard Deviation 45.91	—
Serum Concentration of TB31F 3 hours	2.84 ug/mL Standard Deviation 0.46	21.29 ug/mL Standard Deviation 3.65	75.28 ug/mL Standard Deviation 16.70	210.06 ug/mL Standard Deviation 56.72	—
Serum Concentration of TB31F 6 hours	2.47 ug/mL Standard Deviation 0.27	19.30 ug/mL Standard Deviation 3.86	63.68 ug/mL Standard Deviation 15.15	165.45 ug/mL Standard Deviation 25.71	1.35 ug/mL Standard Deviation 0.64
Serum Concentration of TB31F 24 hours	2.17 ug/mL Standard Deviation 0.18	19.66 ug/mL Standard Deviation 3.37	56.51 ug/mL Standard Deviation 9.61	172.26 ug/mL Standard Deviation 69.10	4.08 ug/mL Standard Deviation 2.30
Serum Concentration of TB31F 48 hours	2.02 ug/mL Standard Deviation 0.15	15.28 ug/mL Standard Deviation 2.38	46.38 ug/mL Standard Deviation 8.61	139.56 ug/mL Standard Deviation 32.76	5.95 ug/mL Standard Deviation 3.29
Serum Concentration of TB31F Day 4	—	—	—	—	9.41 ug/mL Standard Deviation 4.15
Serum Concentration of TB31F Day 7	1.31 ug/mL Standard Deviation 0.09	9.65 ug/mL Standard Deviation 1.83	39.93 ug/mL Standard Deviation 5.61	118.03 ug/mL Standard Deviation 24.28	7.78 ug/mL Standard Deviation 3.30
Serum Concentration of TB31F Day 10	—	—	—	—	8.49 ug/mL Standard Deviation 3.28
Serum Concentration of TB31F Day 14	1.11 ug/mL Standard Deviation 0.16	7.14 ug/mL Standard Deviation 1.44	33.12 ug/mL Standard Deviation 0.55	91.61 ug/mL Standard Deviation 32.05	8.72 ug/mL Standard Deviation 4.90
Serum Concentration of TB31F Day 21	0.91 ug/mL Standard Deviation 0.11	8.07 ug/mL Standard Deviation 4.52	25.01 ug/mL Standard Deviation 4.17	67.87 ug/mL Standard Deviation 15.39	5.88 ug/mL Standard Deviation 2.18
Serum Concentration of TB31F Day 28	0.81 ug/mL Standard Deviation 0.11	4.99 ug/mL Standard Deviation 0.74	19.38 ug/mL Standard Deviation 3.51	69.55 ug/mL Standard Deviation 28.86	5.11 ug/mL Standard Deviation 1.92
Serum Concentration of TB31F Day 56	—	3.08 ug/mL Standard Deviation 0.52	9.52 ug/mL Standard Deviation 2.40	28.28 ug/mL Standard Deviation 6.78	2.86 ug/mL Standard Deviation 1.21
Serum Concentration of TB31F Day 84	0.30 ug/mL Standard Deviation 0.11	1.48 ug/mL Standard Deviation 0.43	4.88 ug/mL Standard Deviation 1.43	16.36 ug/mL Standard Deviation 4.62	1.77 ug/mL Standard Deviation 0.94

SECONDARY outcome

Timeframe: 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.

Population: Day 2, day 4, day 10, and day 14 were not measured for participants in groups 1 to 4, per protocol. For group 1 participants, analyses were not performed after end of infusion due to transmission reducing activity\<80% at this timepoint.

Transmission-reducing activity (TRA) of serum TB31F will be assessed in all subjects throughout the study (until day 84) by standard membrane feeding assays (SMFA). TRA is expressed as the percentage reduction in oocysts in mosquitoes fed on gametocytes in the presence of participants' serum, compared to oocysts in mosquitoes fed on gametocytes in the presence of pooled naïve serum (control). Given the limited precision of low TRA estimates and the historical threshold value of \>80% TRA to support clinical development of transmission-blocking vaccines, TRA \>80% was pre-defined as the efficacy threshold of interest.