The main objective of this study is to establish a controlled human infection model for Chikungunyausing the VLA1553 vaccine.Primary objectives:- To assess the infection rate induced by a single administration of the VLA1553 vaccine- To assess the…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Infection rate: number of healthy volunteers developing viremia divided by
the number of healthy volunteers receiving the vaccine
- Sumptomatic rate: number of healthy volunteers developing vaccine related
symptoms divides by the number of healthy volunteers receiving the vaccine.
Secondary outcome
- Nature, frequency and severity of (serious) adverse events;
- Vital signs;
- Vaccine related symptoms;
- Clinical laboratory tests including hematology and chemistry;
- Physical examination, symptom directed and on indication;
- Concomitant medication;
- Local tolerability of injection site as assessed by a numeric rating scale
(NRS).
- Chikungunya viral load (in both blood and urine) over time as determined by
qPCR.
- Chikungunya viral culture titer, determined by plaque assay, over time.
- Severity, duration and nature of solicited and unsolicited vaccine related
symptoms.
- Occurrence of leukopenia and lymphopenia after administration of the VLA1553
vaccine.
- Seroconversion rate: number of healthy volunteers developing virus
neutralizing antibodies divided by the number of healthy volunteers receiving
the vaccine;
- Titer of virus neutralizing antibodies.
Background summary
Chikungunya is a vector-borne viral disease, increasing in incidence and
expected to spread
worldwide in the coming decades.1 Infection with Chikungunya virus (CHIKV) can
lead to acute
disease, associated with symptoms such as fever, headache, myalgia and skin
rash, but seldomly
with lethal outcome.2 However, up to 60% of infected patients develop
debilitating chronic arthralgias,
which can last up to years. Outbreaks of CHIKV are characterized by a rapid
spread of the virus,
leading to a high disease burden in local populations within a short period of
time.1 The intensification
of global travel and trade has led to an increase in CHIKV outbreaks; a further
increase in the coming
decades is expected due to climate change, as well as the emergence of
alternative CHIKV
transmission vectors beside the Aedes aegypti mosquito, such as Aedes
albopticus, which is more
tolerant to cold temperatures.1 The current need for prophylactic measures
against Chikungunya
disease is urgent and will expectedly increase.
Rapid availability of pharmaceuticals targeting e.g. viruses can limit the
impact of infectious diseases;
in the case of future local outbreaks or pandemics, a health crisis can be
mitigated by swift
development and testing of vaccines.3,4 The controlled human infection model
(CHIM) is an innovative
and effective method for testing pharmaceutics targeting infectious diseases in
early clinical phase.
CHIMs involve active exposure of (healthy) volunteers in a controlled setting,
facilitating close safety
monitoring, as well as the evaluation of efficacy endpoints and extensive
assessment of viral and
immunological endpoints. This allows for an early evaluation and understanding
of the efficacy of new
pharmaceuticals, resulting in early assessment of whether these pharmaceuticals
will be worth their
investment.5,6 CHIMs are often conducted using respiratory viruses, as these
generally cause shortlasting, mild symptoms. Exposing healthy individuals to
CHIKV would be accompanied by a significant
risk (up to 60%) of inducing chronic Chikungunya disease, with symptoms that
can often not be
effectively managed.
Recently, a live attenuated virus (LAV) was approved by the FDA as a vaccine
against Chikungunya.
This vaccine, named VLA1553, showed high effectivity, with immunisation rates
of up to 100%.7,8 In
addition, VLA1553 was demonstrated to cause detectable viremia and mild acute
Chikungunya
associated symptoms, such as fever, headache or joint pains; however, the LAV
did not cause chronic
Chikungunya disease. Passive transfer of VLA1553 induced antibodies to
non-human primates
resulted in protection against Chikungunya associated symptoms after exposure
to CHIKV,
establishing VLA1553 as an effective prophylaxis against natural CHIKV
infection.9 After
revaccination in humans, both viremia and symptoms significantly decreased,
confirming the
immunogenic capacity of VLA1553, as well as its suitability as a challenge
agent to test new therapies
against CHIKV.8 In this study, we aim to establish a controlled human infection
model using the
VLA1553 vaccine as challenge agent, to facilitate efficient and closely
monitored testing of newly
developed drugs against Chikungunya disease.
Study objective
The main objective of this study is to establish a controlled human infection
model for Chikungunya
using the VLA1553 vaccine.
Primary objectives:
- To assess the infection rate induced by a single administration of the
VLA1553 vaccine
- To assess the symptomatic rate induced by a single administration of the
VLA1553 vaccine
Secondary objectives:
- To investigate the safety and tolerability of controlled infection after
vaccination with the VLA1553 live attenuated Chikungunya virus
- To assess the VLA1553 viral kinetics in blood and urine
- To characterize symptoms after VLA1553 challenge
- To assess the immunological response after VLA1553 challenge
Study design
This is an open-label validation study of the VLA1553 Chikungunya vaccine
challenge model. The
study consists of a screening/enrollment period, a baseline visit, a
vaccination period, and a followup visit.The subjects will be monitored for
vaccine-related symptoms, solicited and unsolicited symptoms, adverse events
(AE) and vital signs including tympanic temperature. Routine safety laboratory
assessments (hematology and blood chemistry) will be performed; additional
safety assessments will be performed if deemed
necessary by the investigator. Chikungunya viral load, viral culture and virus
neutralizing antibodies
will be assessed in serum. PBMCs will be collected on timepoints.
Intervention
Subjects will receive the VLA1553 vaccine by intramuscular administration. The
VLA1553 vaccine is a registered vaccine, containing 1 x 10^4 50% Tissue Culture
Infective Dose (TCID50) of live attenuated virus.
Study burden and risks
VLA1553 has a well-established safety profile, assessed in large clinical
trials. Healthy volunteers will receive a single administration containing the
approved dose of 1 x 104 TCID50.
Study participants may develop symptoms related to the vaccine administration,
such as swelling, redness, pain, induration, tenderness or a rash at the
location of administration. In addition, systemic symptoms may emerge in the
first week after vaccine administration; possible systemic symptoms include
headache, fatigue, muscle pain, nausea, vomiting, or joint pain. In clinical
studies, local and systemic symptoms generally subsided after 1-4 days.7 As
with any study involving drug administration, other symptoms may arise that are
not yet described in literature. Finally, volunteers may experience discomfort
during blood sampling.
As VLA1553 has demonstrated high immunogenicity and signs of clinical
protection against Chikungunya disease, volunteers will benefit from receiving
the vaccine in this study. However, as Chikungunya is not endemic in The
Netherlands, and since the longevity of the VLA1553-induced antibodies is not
fully clear, the significance of this benefit remains unclear.
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
Inclusion criteria
- Signed informed consent prior to any study-mandated procedure
- Healthy male or female volunteers, 18 to 64years of age (inclusive) at
screening
- A total body weight >=50 kg and body mass index (BMI) >=18.0 and <=32.0 kg/m2 at
screening;
- All women of childbearing potential must practice effective contraception
during the course of the study and until the last study visit (Day 60);
- Subject is able to communicate well in Dutch with the investigator, has
adequate understanding of the procedures of the study and is willing to comply
with the study procedures and restrictions;
Exclusion criteria
1. Any history or evidence of any clinically significant or currently active
major disease, or condition that, in the opinion of the investigator, may
interfere with a subject completing the study and the necessary investigations
(following a detailed medical history, physical examination, vital signs
(systolic and diastolic blood pressure, and body temperature) and ECG). Minor
deviations from the normal range may be accepted, if judged by the investigator
to have no clinical relevance;
2. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab),
or human immunodeficiency virus antibody (HIV Ab) at screening;
3. Any confirmed or suspected disease or condition associated with immune
system impairment, including auto-immune diseases, HIV, asplenia or recurrent
severe infections;
4. (History of) confirmed or suspected rheumatic disease or condition
associated with joint inflammation or clinically significant
arthritis/arthralgia.
5. Suspected or confirmed history of infection with Chikungunya;
6. Prior participation in another controlled human infection study with
Chikungunya, Yellow Fever or Dengue.
7. Participation in an investigational medical product, vaccine or device study
within 30 days or 5 half-lives prior to the study period (whichever is longer),
or more than 4 times in the past year;
8. Any known history of anaphylaxis or any significant allergy against
vaccines;
9. Use of any medications (prescription or over-the-counter [OTC]), within 14
days prior to vaccine administration, or less than 5 half-lives (whichever is
longer), and during the course of the study. Exceptions are paracetamol (up to
4 gram/day) and contraceptives. Other exceptions will only be made if the
rationale is clearly documented and accepted by the investigator.
10. Use of vitamins or dietary supplements, within 7 days prior to inoculation.
11. Use of chronic (more than 14 days) systemic immunosuppressant medications
within the 3 months prior to vaccine administration, or isolated (non-chronic)
use within 30 days prior to vaccine administration. Incidental use of topical,
intranasal or inhalation corticosteroids may be permitted up to 14 days prior
to vaccine administration (day 1) at the discretion of the investigator;
12. Receipt of any vaccine within 6 weeks prior to vaccine and during the
course of the study;
13. Receipt of blood or blood derived products (including immunoglobulin)
within 180 days prior to vaccine administration;
14. History of abuse of addictive substances (alcohol, illegal substances) or
current use of more than 21 units alcohol per week, drug abuse, or regular user
of sedatives, hypnotics, tranquillizers, or any other addictive agent;
15. Positive test for drugs of abuse at screening or prior to vaccine
administration;
16. Loss or donation of blood over 500 mL within three months (males) or four
months (females)
prior to screening or intention to donate blood or blood products during the
study or within 4
weeks after vaccine administration.
17. Females who are pregnant, breastfeeding, or are planning to become pregnant
during the study; 18. Any known factor, condition, or disease that might
interfere with treatment compliance, study conduct or interpretation of the
results, as deemed by the investigator.
Design
Recruitment
metc-ldd@lumc.nl
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 |
|---|---|
| CCMO | NL88062.058.24 |