The purpose of this study is to compare administration of efgartigimod under the skin (subcutaneously/SC) to administration directly into a blood vessel (intravenously/IV). This is being studied to compare if subcutaneous injection is equally safe…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To demonstrate that the pharmacodynamic (PD) effect of 4 once weekly
subcutaneous (SC) injections of 1000 mg efgartigimod PH20 SC is noninferior to
that of 4 once weekly intravenous infusions (IV) of efgartigimod at a dose of
10 mg/kg by comparing the percentage reduction in total IgG levels after 4
weeks (day 29), ie, one week after the 4th administration, using a
noninferiority margin of 10%.
Secondary outcome
To further compare the PD effect of efgartigimod IV and efgartigimod PH20 SC
over time
- To evaluate the pharmacokinetics (PK) of efgartigimod IV and efgartigimod
PH20 SC
- To evaluate the safety, tolerability, and immunogenicity of efgartigimod IV
and of efgartigimod PH20 SC
Background summary
The actual study will consist of 4 periods during which the volunteer will stay
in the research center for 2, 2, 2, and 7 days (1, 1, 1, and 6 nights)
respectively. This will be followed by 4 days during which you will visit the
research center for a short visit. These short visits will take place on Day
29, 36, 50, 64 and 78.
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 and is expected to improve the symptoms of
these autoimmune diseases.
Study objective
The purpose of this study is to compare administration of efgartigimod under
the skin (subcutaneously/SC) to administration directly into a blood vessel
(intravenously/IV). This is being studied to compare if subcutaneous injection
is equally safe and effective as an intravenous injection.
The effect of the different types of administration of efgartigimod on the
presence of immunoglobulins IgG in your blood will be investigated (this is
called pharmacodynamics). It will also be investigated how quickly and to what
extend efgartigimod is absorbed and eliminated from the body.
We will also investigate how safe the compound efgartigimod is and how well it
is tolerated when it is administered to healthy volunteers.
Efgartigimod has been administered to humans before. It has also been
previously tested in the laboratory and on animals. Efgartigimod PH20 SC will
be tested at a fixed dose, whereas efgartigimod IV will be dosed proportionally
to your weight.
When efgartigimod PH20 is given as a subcutaneous injection, it is administered
in combination with rHuPH20. rHuPH20 is a substance that is used to temporarily
improve the spreading of fluids that are injected under the skin, so it causes
less swelling. It is thought to improve the uptake of the study compound in the
body. rHuPH20 has been given with other approved drugs for this purpose before.
This study will be performed in up to 54 healthy male and female volunteers.
Study design
Efgartigimod will be given as either an intravenous infusion (solution of the
compound that will be administered directly in a blood vessel) or as an
injection under the skin (subcutaneous).
Over the course of the study, the volunteer will receive 4 doses. The volunteer
will receive 1 dose every 7 days.
There are 2 possible treatments:
• 10 mg/kg* efgartigimod directly into a blood vessel (intravenously) as a
1-hour infusion
• 1000 mg efgartigimod combined with 2000 U/mL rHuPH20 as a single injection
under the skin (subcutaneously)
* This means that 10 mg of efgartigimod will be administered per 1 kg of body
weight, so the actual dose will depend on the volunteers body weight
The volunteer will receive either 4 doses intravenously or 4 doses
subcutaneously. the volunteer will be randomly assigned to one of the
treatments. Neither you nor the responsible study doctor decide which treatment
you receive.
Intervention
Efgartigimod will be given as either an intravenous infusion (solution of the
compound that will be administered directly in a blood vessel) or as an
injection under the skin (subcutaneous).
Study burden and risks
The study compound may cause side effects.
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.
Efgartigimod has been investigated in 3 healthy volunteer clinical trials 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 subjects 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.
Patients with myasthenia gravis who received 10 mg/kg efgartigimod
intravenously for 4 weeks, showed a decrease in IgG antibodies and improvement
of symptoms, and treatment with efgartigimod was well tolerated and safe. The
most common side effects were headache, decreases in white blood cell counts,
increases in levels of a blood test marker for inflammation (C-reactive protein
levels), injection site bruise, fatigue, runny nose/common cold, and
mouth/throat discomfort. Some of the observed side effects were observed in the
placebo group (a dummy medicine that mimics the study compound, but with no
active ingredient), as well as in doses higher than the dose that will be used
in this study.
In patients with immune thrombocytopenia, treatment with 5 or 10 mg/kg
intravenous efgartigimod for 4 weeks resulted in a decrease in IgG antibodies
and an increase in blood platelets (the blood cells that are destroyed by the
disease). Treatment with efgartigimod was found to be safe and well tolerated.
The few observed side effects were petechiae (tiny red patches on the skin or
inside the mouth or eyelids), high blood pressure, and vomiting.
The study compound can also cause an immune reaction. This can be fever,
itching, rashes and, in severe cases, an allergic/anaphylactic reaction.
rHuPH20 is a permeation (diffusion) enhancer with a well-characterized
nonclinical and clinical safety profile that allows the rapid delivery of large
volumes of fluid and/or co-administered drugs under the skin (subcutaneous). In
clinical studies, the subcutaneous administration of rHuPH20 in combination
with other substances was well-tolerated. Adverse effects may include mild and
short-lived injection site reactions, such as redness, swelling, pain and
itching. Adverse events in these trials were related to the co-administered
drug or have been associated with the rapid introduction of a relatively large
volume of fluid in the subcutaneous space. rHuPH20 is co-formulated or
co-administered with several products in the US and EU (e.g., Herceptin® SC,
MabThera® SC, HyQvia®). The study compound may also have side effects that are
still unknown.
Industriepark Zwijnaarde 7
Zwijnaarde 9052
BE
Industriepark Zwijnaarde 7
Zwijnaarde 9052
BE
Listed location countries
Age
Inclusion criteria
Healthy, adult males and females of non-childbearing potential between 18-65
years of age, inclusively, with a BMI between 18-30 kg/m2, and body weight
between 50-100 kg.
Exclusion criteria
1. The subject has previously participated in clinical studies with
efgartigimod (ARGX-113).
2. The subject has a known hypersensitivity to one of the components in the
IMP, or a history of severe allergic or anaphylactic reactions, in the opinion
of the investigator.
3. The subject tests positively at screening for any of the following
conditions:
a. an active hepatitis B infection (acute or chronic) at screening as
determined by HepB serology
b. Hepatitis C Virus (HCV): serology positive for HCV-Ab
c. HIV positive serology
4. Subjects with clinically significant active or chronic uncontrolled
bacterial, viral, or fungal infection at screening.
5. Subjects with clinical evidence of other significant serious diseases,
subjects who underwent a recent major surgery, or any other reason which could
confound the results of the trial or put the subject at undue risk.
For more exclusion criteria see 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 | EUCTR2019-004985-17-NL |
| CCMO | NL72946.056.20 |