The sponsor is developing a compound (PB006) similar to Tysabri® (natalizumab, hereafter referred to as Tysabri). As part of medical-scientific studies to confirm the similarity of the two compounds, the Sponsor wants to compare PB006 with EU-…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• To demonstrate pharmacokinetic comparability of PB006 to US-licensed Tysabri®
in terms of AUC0-inf of total natalizumab
• To demonstrate pharmacokinetic comparability of PB006 to EU-approved Tysabri®
in terms of AUC0-inf of total natalizumab
• To demonstrate comparability pharmacokinetics of US-licensed and EU-approved
Tysabri® in terms of AUC0-inf of total natalizumab
• To demonstrate pharmacodynamic comparability of PB006 to pooled reference
(US-licensed Tysabri® and EU-approved Tysabri®) in terms of baseline-adjusted
AUEC0-12w of CD19+
• To demonstrate pharmacodynamic comparability of PB006 to US-licensed Tysabri®
and EU-approved Tysabri® in terms of parameters of α4-integrin receptor
saturation
Secondary outcome
• To support pharmacokinetic comparability of PB006 to US-licensed Tysabri® and
EU-approved Tysabri® in terms of secondary PK parameters of total natalizumab
• To support pharmacokinetic comparability of PB006 to US-licensed Tysabri® and
EU-approved Tysabri® in terms of PK parameters of unexchanged natalizumab
• To support comparability of PB006 to US-licensed Tysabri® and EU-approved
Tysabri® in terms of secondary PD parameters of baseline-adjusted CD19+
• To support pharmacodynamic comparability of PB006 with US-licensed Tysabri®
and EU-approved Tysabri® in terms of sVCAM decrease
• To support pharmacodynamic comparability of PB006 with US-licensed Tysabri®
and EU-approved Tysabri® in terms of sMAdCAM decrease
• To support pharmacodynamic comparability of PB006 to US-licensed Tysabri® and
EU-approved Tysabri® in terms of PD parameters of CD34+
• To support comparable immunogenicity profiles of PB006 with US-licensed
Tysabri® and with EU-approved Tysabri®
• To support comparable safety and tolerability profiles of PB006 and both
US-licensed Tysabri® and EU-approved Tysabri®
Background summary
The sponsor is developing a compound (PB006) similar to Tysabri. As part of
medical-scientific studies to confirm the similarity of the two compounds, the
sponsor wants to compare PB006 with EU-approved and US licensed Tysabri.
Tysabri is a drug approved in Europe and the USA for the treatment of Multiple
Sclerosis (MS) and in the USA also for the treatment of Crohn*s Disease. MS
causes inflammation in the brain that damages the nerve cells. Symptoms of MS
can include: walking problems, numbness in the face, arms or legs, problems
with vision, tiredness, feeling off-balance or light headed, bladder and bowel
problems, difficulty in thinking and concentrating, depression, acute or
chronic pain, sexual problems, stiffness, and muscle spasms.
The active ingredient of Tysabri is natalizumab which is an antibody. These
antibodies work by binding to proteins in the body so that the harmful effect
of that protein is removed. Tysabri stops the cells that cause inflammation
from going into the brain. This reduces nerve damage caused by MS.
Study objective
The sponsor is developing a compound (PB006) similar to Tysabri® (natalizumab,
hereafter referred to as Tysabri). As part of medical-scientific studies to
confirm the similarity of the two compounds, the Sponsor wants to compare PB006
with EU-approved and US-licensed Tysabri.
The purpose of this study is to investigate how quickly and to what extent
PB006 is absorbed and eliminated from the body compared to the EUapproved
Tysabri, and US licensed Tysabri. It will also be investigated how the body
responds to PB006 compared to the two Tysabri products. In addition, the study
will assess the safety and tolerability profiles of PB006 and both Tysabri
products.
Study design
The actual study will consist of 1 period during which the volunteer will stay
in the research center for 10 days (9 nights). This will be followed by 9 days
during which the volunteer will visit the research center for a short visit.
These short visits will take place on Day 15, 22, 29, 36, 43, 57, 71, 78, and
85.
The volunteer will receive PB006, EU approved Tysabri, or US-licensed Tysabri
as an intravenous infusion over 60 minutes. The dose the volunteer will receive
is 3 mg/kg body weight.
Whether the volunteer will receive PB006, EUapproved Tysabri, or US-licensed
Tysabri will be determined by chance. PB006, EU approved Tysabri, and
US-licensed Tysabri will each be given to 120 volunteers. Neither the
volunteer, nor the PI knows which treatment will be dosed.
Intervention
The volunteer will receive PB006, EU approved Tysabri, or US-licensed Tysabri
as an intravenous infusion over 60 minutes. The dose he or she will receive is
3 mg/kg body weight.
Study burden and risks
The study compound may cause side effects, though not everybody will be
affected.
The following side effect is most often reported (by more than 1 in 10 people)
with Tysabri:
- Infusion-related side effects
The following side effects have been reported by up to 1 in 10 people in
medicalresearch studies with Tysabri:
- Urinary tract infection
- Sore throat and runny or blocked up nose
- Shivering
- Itchy rash (hives)
- Headache
- Dizziness
- Feeling sick (nausea)
- Being sick (vomiting)
- Joint pain
- Fever
- Tiredness
The following side effects have been reported in a previous clinical study on
healthy volunteers with PB006:
- Headache
- Fatigue
- Malaise
- Nausea
- Vomiting
The study compound may also have side effects that are still unknown.
Drawing blood and/or insertion of the indwelling cannula may be painful or
cause some bruising.
During the course of the study (from screening to follow-up), we will take a
maximum of 600 milliliters of blood from the volunteer.
To make a heart tracing, electrodes will be pasted at specific locations on the
arms, chest and legs. Prolonged use of these electrodes can cause skin
irritation.
A sample for the coronavirus test will be taken from the back of the nose
and/or throat using a swab. Taking the sample only takes a few seconds, but can
cause discomfort and can give an unpleasant feeling. Taking a sample from the
back of your throat may cause the volunteer to gag. When the sample is taken
from the back of the nose, you may experience a stinging sensation and the eyes
may become watery.
Possible risk of development of progressive multifocal leukoencephalopathy (PML)
JCV is a common virus that is generally harmless to humans and often acquired
during childhood. It does not cause symptoms in people whose immune system
functions normally. However, JCV can cause PML in people with weakened immune
systems. Causes of a weakened immune system may include HIV infection, leukemia
or lymphoma, or taking a medication such as Tysabri. Testing positive for JCV
antibodies means that a person has been exposed to JCV in the past.
If the volunteer has been treated with Tysabri or PB006 or with an
immunosuppressant medication or in case the volunteer should test positive for
JCV, he/she will not be eligible to participate in this study. Therefore, all
risk factors for PML will not be present in order to reduce the potential risk
as much as possible.
PML is a rare disorder in which the coating (myelin) of brain nerve fibers gets
damaged. The most prominent symptoms of PML are clumsiness, progressive
weakness, visual changes, speech changes, and sometimes personality changes.
PML can result in death or variable degrees of neurological disability. There
are no cases of PML known in healthy volunteers without JCV antibodies, after
administration of Tysabri or PB006.
In people testing negative for JCV, the incidence of PML is estimated at less
than 1 in 10.000. People with all three known risk factors have a greater
estimated risk of PML. The risk factors are:
- The presence of anti-JCV antibodies.
- Longer duration of Tysabri treatment, especially beyond 2 years.
- Prior treatment with an immunosuppressant medication (e.g., mitoxantrone,
azathioprine, methotrexate, cyclophosphamide, or mycophenolate mofetil).
ul. Trzy Lipy 3A
Gdansk 80-172
PL
ul. Trzy Lipy 3A
Gdansk 80-172
PL
Listed location countries
Age
Inclusion criteria
1. The subject is male/female and 18 to 54 years of age, inclusive
2. The subject is healthy as determined by their medical history, a physical
examination, vital signs, an ECG and clinical laboratory testing
3. The subject has a BMI within the range of 18.5 to 30.0 kg/m2, inclusive and
a body weight of 50 - 92 kg, inclusive
4. The subject provided written, informed consent prior to any clinical
study-specific procedures.
5. Male subject (if his female spouse/partner is of childbearing potential)
must confirm that he is using two acceptable methods for contraception during
the study and for 3 months after final study drug administration. Male subject
should confirm he has informed his partner of participation in the study and
the need to avoid pregnancy. Surgically sterilised male subjects do not require
additional use of contraception.
Subject needs, after implementation of amendment 3, 2 negative PCR SARS-CoV-2
tests before dosing with natalizumab (after admission to the clinic and prior
to dosing).
Further criteria apply
Exclusion criteria
1. Any known exposure to natalizumab, alemtuzumab, ocrelizumab, daclizumab,
rituximab, ofatumumab or obinutuzumab or any other B- and T-cell targeting
therapies.
2. Any known exposure to immunosuppressive agents
3. Known or suspected hypersensitivity to natalizumab, or any components of the
formulation used
4. Any exposure to steroids prior to dosing, to agents such as interferon-β,
glatiramer acetate, fingolimod or laquinimod, to teriflunomide or to dimethyl
fumarate
5. Plasma exchange within 3 weeks prior to dosing.
Exclusion of subjects with a history or evidence of SARS-CoV-2 infection in the
last month prior screening 1 or having been in confirmed contact with
SARS-CoV-2 positive subjects in the last 2 weeks before dosing (after
implementation of amendment 3).
Further criteria apply
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 | EUCTR2019-003874-15-NL |
| CCMO | NL71674.056.19 |