The purpose of this study is to investigate the effect of the study compound efgartigimod on the immune system's response to vaccination with Pneumovax 23. We also investigate how safe efgartigimod is and how well it is tolerated when it is…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the humoral immune response to the PNEUMOVAX 23 vaccine in healthy
participants receiving efgartigimod intravenously (IV)
Secondary outcome
- To evaluate the safety and tolerability of efgartigimod IV in healthy
participants vaccinated with PNEUMOVAX 23
Background summary
Efgartigimod is a new compound that may potentially be used for the treatment
of autoimmune diseases such as myasthenia gravis, pemphigus, and immune
thrombocytopenia. Autoimmune diseases are diseases where antibodies produced by
the body*s immune system attack the body*s own cells. The immune system is the
body*s defense system that protects against invading pathogens.
In the autoimmune diseases myasthenia gravis, pemphigus and immune
thrombocytopenia the immune system specifically produces so-called IgG
antibodies. In myasthenia gravis these IgG antibodies affect muscle cells so
that these cannot contract anymore. This causes muscle weakness in the arms and
legs, or in extreme cases it may affect the muscles involved in breathing. In
immune thrombocytopenia these antibodies attack blood platelets (the cells in
the blood that are involved in blood clotting), which results in an increased
tendency to bleed and bruise. In pemphigus the IgG antibodies attack the
*glue* (desmoglein) that holds the skin cells together, causing blisters.
Efgartigimod promotes the break-down of these IgG antibodies so they can no
longer attack the body*s own cells. It is expected to improve the symptoms of
these autoimmune diseases
In this study we will investigate to what extent the study compound affects the
immune system*s response (eg, IgG levels to a vaccine. This will be tested with
the pneumococcal vaccine Pneumovax 23. It protects against pneumococci
infection. The pneumococcus is a bacterium that can for example cause
pneumonia. If this bacterium enters the bloodstream or nervous system, people
can contract meningitis from it. Vaccination is the best protection against
pneumococcal disease. Vaccination with Pneumovax 23 normally will result in an
increase of IgG antibodies against pneumococci and this response could be
impacted by Efgartigimod as it promotes the breakdown of all IgG antibodies.
Study objective
The purpose of this study is to investigate the effect of the study compound
efgartigimod on the immune system's response to vaccination with Pneumovax 23.
We also investigate how safe efgartigimod is and how well it is tolerated when
it is used by healthy participants. In addition, we look at the presence of
immunoglobulins IgG (antibodies) in your blood (this is called
pharmacodynamics). Please see Section 3.0 for more information on IgG.
We compare the effects of efgartigimod with the effects of a placebo. A placebo
is a compound without any active ingredient. Please note that when the term
*study compound* is used in this document, we mean efgartigimod, placebo, or
both.
Efgartigimod has been administered to humans before (see Section 6.0 for an
overview). It has also been previously tested in the laboratory and on animals
Pneumovax 23 is the latest vaccine against pneumococci infection and is already
approved for use in humans.
Study design
The examination lasts a maximum of 12 weeks from the inspection to the
follow-up check.
We first want to know if the volunteer is suitable to participate. The
researcher will first discuss the ICF document with the volunteer. When the
volunteer decides to participate in the study, the researcher will sign this
document together with the volunteer.
The researcher then performs the examination.
We test female participants for pregnancy. Female participants cannot
participate in the study if they are pregnant or breastfeeding.
It is also possible that a volunteer is healthy, but is not suitable to
participate. For example, because the volunteer is too heavy or too light
according to the requirements of the study.
For the research it is necessary that the volunteer stays in the research
center for 4 periods of 2 days (1 night). After this there are 4 more visits to
the research center. These visits are on Day 36, 50 and 64, with an additional
visit on either Day 29 or Day 43 (depending on which group the volunteer is in).
The study drug is given on Days 1, 8, 15, and 22. The volunteer is expected at
the study center the day before each dose, i.e. on Days -1, 7, 14, and 21. The
volunteer should then be at approximately 11:00 a.m. o'clock in the morning
report. The entry time can be adjusted. If this happens, the volunteer will be
informed in advance. After each administration, the volunteer should remain in
the study center for observation for at least 30 minutes and then go home.
For the visits during the follow-up period, the volunteer is expected at the
research center between 1:00 PM and 3:30 PM. We make an appointment for a
specific time within this time frame.
The volunteer will receive efgartigimod or placebo as an intravenous infusion.
The infusion lasts 1 hour.
The Pneumovax 23 vaccine is given as an injection with a needle into the muscle
of the volunteer's upper arm.
Whether the volunteer receives efgartigimod or placebo is determined by lottery.
Out of a total of approximately 36 participants, 24 participants will receive
efgartigimod and 12 participants will receive placebo. Both the volunteer and
the investigators know whether the volunteer is receiving efgartigimod or the
placebo; open label research.
The study drug is given 4 times: on Days 1, 8, 15 and 22. Depending on which
group the volunteer is in, the Pneumovax 23 vaccine is given either before the
last study drug administration on Day 22, or at the visit on Day 36 (two weeks
after the last dose of study drug).
There are 3 possible treatments in this study. The treatment the volunteer
receives is determined by drawing lots.
Intervention
the volunteer will be given efgartigimod or placebo as an intravenous infusion
(solution of the compound that will be administered directly in a blood
vessel). The infusion takes 1 hour.
The Pneumovax 23 vaccine will be given as an injection with a syringe in the
muscle of the upper arm of the volunteer.
Whether the volunteer will receive efgartigimod or placebo will be determined
by chance. Of the total of approximately 36 participants, 24 participants will
receive efgartigimod and 12 participants will receive placebo. Both the
volunteer and the investigators know if efgartigimod or placebo will be
administered; open-label study.
The study compound will be given 4 times: on Day 1, 8, 15, and 22. Depending on
what group the volunteer is in, the Pneumovax 23 vaccine will be given either
prior to the last administration of the study compound on Day 22, or on the
visit on Day 36 (two weeks after the last study compound dose).
There are three possible treatments in this study. Which treatment the
volunteer will receive will be determined by drawing lots.
Study burden and risks
Taking part in a clinical study involves some risks and possible discomfort.
All medications can cause side effects (unwanted or unpleasant effects) in some
people. Not all of the side effects that the study compound can cause may be
known at this time. It is very important that the volunteer reports anything
they feel to their responsible doctor. The volunteer should not wait until the
next scheduled visit.
Efgartigimod has been investigated in 3 other clinical trials with healthy
volunteers and was found to be well-tolerated. Efgartigimod has been
administered to healthy volunteers intravenously (directly into a blood vessel)
in doses up to 50 mg/kg. A few subjects treated with doses of 25 mg/kg or 50
mg/kg showed abnormalities in white blood cell counts, but they went back to
normal within 2 to 4 days after stopping with the treatment. Also, some
volunteers showed increased C-reactive protein levels (which is a marker of
inflammation/infection), but these levels went back to normal within 3 to 6
days after stopping with the treatment, and there were no signs of infection or
inflammation. Efgartigimod has been administered to healthy volunteers
subcutaneous (directly into skin) in doses up to 10 mg/kg and was found to be
well-tolerated.
The most commonly reported side effects in healthy subject studies with
efgartigimod were:
• headache
• decreases in white blood cell counts
• increase in level of a blood test marker for inflammation (C-reactive protein)
• injection site bruise
• Injection site redness
• fatigue
• common cold
• mouth/throat discomfort
• back pain
Some of these side effects were observed in the placebo group, and some were
observed in doses higher than the dose that will be used in this study.
The most commonly reported side effects in other studies in subjects with
Thrombocytopenia and Myasthenia Gravis included:
• headache
• common cold
• diarrhea
• upper respiratory tract infection
• nausea
• urinary tract infection
• muscle pain
• mouth/throat discomfort
Most of these side effects were mild to moderate in intensity, resolved quickly
and were assessed as not related to the study compound. Most common side
effects that were considered related to the study compound included
inflammation of airway passages, upper respiratory tract infection, urinary
tract infection, headache, and muscle pain.
The study compound can also cause an immune reaction. This can be fever,
itching, rashes and, in severe cases, an allergic/anaphylactic reaction. Your
responsible doctor will ask you if you have ever had any allergic reactions.
It is possible that the body of the volunteer produces antibodies against the
study compound. These antibodies can make them less sensitive to the study
compound in the future. It is not expected that the presence of these
antibodies will have consequences for their health.
The study compound may also have (serious) side effects that are still unknown.
In addition to unknown side effects, there is a (small) chance that an allergic
reaction will occur. This can be caused by the study compound or other
ingredients that are used to prepare the formulation.
If during the study more information becomes available regarding side effects
that may be related to the study compound, the responsible doctor will inform
the volunteer about this.
The Pneumovax 23 vaccine may also cause side effects.
The most frequent ones (reported in more than 10% of participants vaccinated
with Pneumovax 23 for the first time in a drug study) are:
• Injection-site pain/soreness/tenderness
• Injection-site swelling/induration
• Headache
• Reddening of the skin at injection-site
• Lack of energy / fatigue
• Myalgia
Industriepark Zwijnaarde 7
Ghent 9052
BE
Industriepark Zwijnaarde 7
Ghent 9052
BE
Listed location countries
Age
Inclusion criteria
1. At least18 years of age at the time of signing the informed consent form
(ICF)
2. Healthy as determined by medical evaluation including medical history,
physical examination, laboratory tests, and cardiac monitoring
3. Body mass index (BMI) between 18 kg/m2 to 30 kg/m2 (inclusive)
4. Contraceptive use by men and women should be consistent with local
regulations regarding the methods of contraception for those participating in
clinical studies.
5. Capable of giving signed informed consent as described in Appendix 1,
Section 10.1.3, which includes compliance with the requirements and
restrictions listed in the ICF and in this protocol
6. Abstains from smoking for at least 3 months prior to screening
7. Negative urine drug screen (amphetamines, barbiturates, benzodiazepines,
cannabis, cocaine, opiates, methadone, and tricyclic antidepressants) at
screening and on day -1
8. Negative alcohol urine test at screening and on day -1
9. Agrees to restrict excessive strenuous physical activities 96 hours prior to
screening, 96 hours prior to the visits in the treatment period (D-1, D7, D14,
and D21), and 96 hours prior to the visits in follow-up period
Exclusion criteria
1. Clinically significant active or chronic bacterial, viral, including or
fungal infection at day -1
2. History of malignancy unless deemed cured by adequate treatment with no
evidence of recurrence for >=3 years before the first administration of study
intervention. Participants with the following
cancers can be included at any time:
a. Adequately treated basal cell or squamous cell skin cancer
b. Carcinoma in situ of the cervix
c. Carcinoma in situ of the breast
d. Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
3. Clinical evidence of other significant serious diseases, a recent major
surgery, or any other condition that, in the opinion of the investigator, could
confound the results of the study or put the participant at undue risk
4. Use of an investigational product within 2 months or 5 half-lives (whichever
is longer) before the first dose of study intervention
5. Use of any monoclonal antibody within 3 months prior to the initial study
intervention administration
For more exclusion criteria see 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 |
|---|---|
| EudraCT | EUCTR2021-004878-53-NL |
| CCMO | NL79381.056.21 |