The purpose of this study is to investigate the safety and tolerability of the new compound PB006 (natalizumab) when it is administered to healthy volunteers. PB006 has not been administered to humans before. It has been previously tested in the…
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- safety
- tolerability
Secondary outcome
N/A
Background summary
The sponsor is developing PB006, a compound similar to Tysabri. In preparation
for medical-scientific studies to confirm the similarity of the two compounds,
the Sponsor wants to study the safety of PB006.
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
seeing things,
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 PB006 and 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 purpose of this study is to investigate the safety and tolerability of the
new compound PB006 (natalizumab) when it is administered to healthy volunteers.
PB006 has not been administered to humans before. It has been previously tested
in the laboratory and on animals. PB006 is a biosimilar to Tysabri®, this means
it contains the same active substance (natalizumab) as Tysabri, a drug marketed
and used for the treatment of patients with Multiple Sclerosis (MS).
This study will be performed in 10 healthy male/female volunteers. The study
will be performed in 1 part.
Study design
The study will consist of 1 period during which the volunteer will stay in the
research center for 4 days (3 nights). This will be followed by 2 days during
which you will visit the research center for a short visit. These short visits
will take place on Day 7 and 14.
The volunteer will be given 300 mg PB006 as an intravenous infusion (solution
of the compound that will be administered directly in a blood vessel),
administered over 60 minutes.
For safety reasons, initially 2 volunteers will receive the study compound at
least 2 hours apart. After administration, the safety and tolerability of the
study compound in these 2 volunteers will be closely monitored. If there are no
concerns about the safety and tolerability 48 hours after administration, then
the remaining 8 volunteers will receive the study compound. The study will be
discontinued if, in the opinion of the responsible doctor, unacceptable side
effects appear.
Intervention
The volunteer will be given 300 mg PB006 as an intravenous infusion (solution
of the compound that will be administered directly in a blood vessel),
administered over 60 minutes.
For safety reasons, initially 2 volunteers will receive the study compound at
least 2 hours apart. After administration, the safety and tolerability of the
study compound in these 2 volunteers will be closely monitored. If there are no
concerns about the safety and tolerability 48 hours after administration, then
the remaining 8 volunteers will receive the study compound. The study will be
discontinued if, in the opinion of the responsible doctor, unacceptable side
effects appear.
Study burden and risks
As with any drug, the study compound may cause side effects, though not
everybody will be affected.
As PB006 will be administered to man for the first time in this study, side
effects of PB006 in man have not been reported to date. However, PB006 is
highly similar to Tysabri (natalizumab) that has been marketed and given to
patients.
The following side effects are most frequently observed (in 1 in 10 people or
more) in medical-research studies with Tysabri/natalizumab:
• 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
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 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.
In people testing negative for JCV, the incidence of PML is estimated at less
than 1 in 10,000. However, people with all three known risk factors have a
higher 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).
Possible discomforts due to procedures
Drawing blood and/or insertion of the indwelling cannula (tube in an arm vein)
may be painful or cause some bruising.
In total, we will take about 100 milliliters (mL) of blood from the volunteer.
This amount does not cause any problems in adults.
To make a heart tracing, electrodes (small, plastic patches) will be pasted at
specific locations on the arms, chest and legs. Prolonged use of these
electrodes can cause skin irritation (rash and itching).
Bergfeldstrasse 9
Holzkirchen 83607
DE
Bergfeldstrasse 9
Holzkirchen 83607
DE
Listed location countries
Age
Inclusion criteria
- healthy males and females
- 18-65 years, inclusive
- BMI: 18.5-32.0 kg/m2
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 (e.g. methotrexate, cyclosporine, azathioprine, mitoxantrone, tacrolimus)
3. Known or suspected hypersensitivity to natalizumab, or any components of the formulation used (L-histidine/L-histidine hydrochloride, sodium chloride, polysorbate 80).
4. Any exposure to steroids within one month prior to dosing, to agents such as interferon-β, glatiramer acetate, fingolimod laquinimod within the last 2 months, toteriflunomide during the last 3.5 months, or to dimethyl fumarate within 6 months prior to dosing.
5. Positive test for anti-JCV antibodies [screening 1].
6. Female subject who has been pregnant within 6 months prior to screening 2, or breastfeeding or lactating within 3 months prior to screening 2.
7. Any of the liver enzymes (AST, ALT, alkaline phosphatase [ALP],
gamma-glutamyltransferase [GGT]) and TBL above the ULN. In such a case the assessment may be repeated once. [Screening 2 and Day-1]
8. Any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).;Suffering from hepatitis B, hepatitis C, cancer or HIV/AIDS. In case of participation in another drug study within 60 days before the start of this study.
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 | EUCTR2018-004761-13-NL |
| CCMO | NL68917.056.19 |