(protocol section 2) This phase 1 study aims to assess the safety and tolerability of monoclonal antibody TB31F administered intravenously or at escalating dose levels or subcutaneously in healthy, malaria naïve, adults. This study will also…
ID
Source
Brief title
Condition
- Other condition
- Protozoal infectious disorders
Synonym
Health condition
malaria
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
(protocol section 8.1.1)
- Number and severity of solicited local adverse events of all severities from
first product administration through day 7;
- Number and severity of solicited general AEs from first product
administration through day 28;
- Number and severity of unsolicited adverse events from first product
administration through end of study;
- Number and severity of serious adverse events from first product
administration through end of study.
Secondary outcome
(protocol section 8.1.1)
- TB31F serum concentration at each dose level through end of study;
- Percentage of transmission reducing activity at different time points by
SMFA.
Background summary
(protocol section 1.1) A major challenge for malaria elimination is the highly
efficient spreading of malaria parasites. Circulating gametocytes do not cause
clinical pathology or symptoms but play an essential role in the onward
transmission of malaria infections. Gametocytes of P. falciparum synthesize
Pfs48/45. Male gametocytes lacking Pfs48/45 are unable to bind to female
gametocytes in the mosquito gut. A transmission blocking medicine aims to
prevent the sexual development of parasites in the mosquito*s midgut.
Antibodies (Abs) in the blood are ingested during the blood meal of the
mosquito, preventing sporozoite development. TB31F interrupts transmission of
P. falciparum in the Standard Membrane Feeding Assay.
Study objective
(protocol section 2) This phase 1 study aims to assess the safety and
tolerability of monoclonal antibody TB31F administered intravenously or at
escalating dose levels or subcutaneously 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.
Study design
(see protocol section 3) The trial will be carried out by the Radboud
University Medical Center (Radboudumc). Five groups will receive a single dose
of mAb TB31F administered by intravenous infusion or subcutaneously. 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 (n=5) will receive 100mg.
Twentyfive (n=25) subjects will be enrolled, as well as 1 reserve subject per
group. Safety follow-up will be done at following times: 0 hours, end of
infusion (EOI), 1, 3, 6 and 24 hours after product administration, and on days
2, 7, 14, 21, 28, 56 and 84 after product administration. Group 5 subjects will
have an additional follow-up visit on day 4 and day 10 after administration.
All subjects will be followed for approximately 84 days after mAb TB31F
administration.
Intervention
Single intravenous or subcutaneous administration of TB31F
Study burden and risks
There are no benefits to participating in this study. Subjects are not
protected against malaria after participating. TB31F has not been administered
in humans before, therefore we do not know what side effects TB31F can give.
Participating in this trial includes the burden mAb TB31F administration,
placement of intravenous infusion catheter(s), multiple blood sampling tests,
possible side effects from premedication, frequent follow-up visits, physical
examinations, screening for HIV, Hepatitis B and Hepatitis C, a pregnancy test
(for females), filling out a study journal, possible COVID-19 diagnostics and
abiding to all study rules. However, the information that we get from this
study will help us further in the development of transmission-blocking
interventions against malaria.
Geert Grooteplein Zuid 28
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 28
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
* 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.
* 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 till day +7 after mAb TB31F administration.
* Subject is a male or non-pregnant female age * 18 and * 35 years and in good
health at time of mAb administration.
* 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.
* Female subjects of non-childbearing potential may be enrolled in the study.
All subjects must agree to use continuous adequate contraception until 2 months
after completion of the study.
Exclusion criteria
(Protocol section 4.3.)
* 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:
o 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).
o Fever * 38.0°C (100.4°F).
o Any abnormal and clinically significant baseline laboratory screening tests
(appendix 1).
* 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, ii) antibiotics, 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.
* Positive urine toxicology test for cannabis, cocaine or amphetamines at
screening or at inclusion.
* 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.
* History of adverse reactions to monoclonal antibodies
* Prior receipt of an investigational antimalarial monoclonal antibody.
* Administration of immunoglobulins 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 CHMI.
* Body weight > 115 kg
* Being an employee or student of the department of Medical Microbiology or
Medium Care of the Radboudumc.
* History of drug or alcohol abuse interfering with normal function in the
period of one year prior to study onset.
* 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov (NCT04238689) |
| EudraCT | EUCTR2019-001904-39-NL |
| CCMO | NL69779.091.19 |