The sponsor is developing a compound (PB016) similar to Entyvio® (vedolizumab, hereafter referred to as Entyvio). As part of medical-scientific studies to confirm the similarity of the biological products, the sponsor wants to compare PB016 with EU-…
ID
Source
Brief title
Condition
- Other condition
- Gastrointestinal ulceration and perforation
Synonym
Health condition
ulcerative colitis and Crohn's disease and pouchitis
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Using the intravenous (IV) presentation:
• To demonstrate pharmacokinetic (PK) comparability of PB016 to US licensed
Entyvio® in terms of AUC0 last of vedolizumab
• To demonstrate PK comparability of PB016 to EU approved Entyvio® in terms of
AUC0-last of vedolizumab
• To demonstrate PK comparability of EU approved Entyvio® to US-licensed
Entyvio® in terms of AUC0-last of vedolizumab for scientific bridge
• To demonstrate PK comparability of PB016 to US licensed Entyvio® in terms of
AUC0 inf of vedolizumab
• To demonstrate PK comparability of PB016 to EU approved Entyvio® in terms of
AUC0 inf of vedolizumab
• To demonstrate PK comparability of EU approved Entyvio® to US-licensed
Entyvio® in terms of AUC0-inf of vedolizumab for scientific bridge
Secondary outcome
• To demonstrate PK comparability of PB016 to US licensed Entyvio® in terms of
Cmax of vedolizumab
• To demonstrate PK comparability of PB016 to EU approved Entyvio® in terms of
Cmax of vedolizumab
• To demonstrate PK comparability of EU approved Entyvio® to US-licensed
Entyvio® in terms of Cmax of vedolizumab
• To support comparable PK profiles of PB016 with US-licensed Entyvio® and with
EU approved Entyvio in terms of tmax, t1/2, and clearance
• To support comparable immunogenicity profiles of PB016 with US-licensed
Entyvio® and with EU approved Entyvio®
• To support comparable safety and tolerability profiles of PB016 and both US
licensed Entyvio® and EU approved Entyvio®
Background summary
Entyvio is a drug approved in Europe, the USA, and Australia for the treatment
of ulcerative colitis and Crohn*s disease and in the EU also for the treatment
of pouchitis. In this study, Entyvio sold in Australia will be given to you as
EU-approved Entyvio. Ulcerative colitis causes inflammation in the colon, while
in Crohn*s disease inflammation is seen anywhere in the digestive tract. In
spite of Crohn's disease and ulcerative colitis being very different diseases,
both have the following symptoms: abdominal pain, diarrhea, rectal bleeding,
severe internal cramps/muscle spasms in the region of the pelvis and weight
loss. Pouchitis is an inflammation of the pouch, an artificial rectum
surgically created out of gut tissue in ulcerative colitis patients. The rectum
is the storage area before stool leaves the body.
The active ingredient of Entyvio is vedolizumab, which is an antibody. These
antibodies work by binding to proteins in the body so that the harmful effect
of that protein is removed. Entyvio stops the cells that cause inflammation
from going into the gastrointestinal tract. This reduces damage to the
gastrointestinal tract caused by ulcerative colitis and Crohn*s disease.
The study compound remains in the body for a long time. The half-life, that is
the time it takes for the amount of the study compound in the blood to be
halved, is approximately 26 days for vedolizumab. It is expected that the
half-life of PB016 will be similar.
Study objective
The sponsor is developing a compound (PB016) similar to Entyvio® (vedolizumab,
hereafter referred to as Entyvio). As part of medical-scientific studies to
confirm the similarity of the biological products, the sponsor wants to compare
PB016 with EU-approved and US-licensed Entyvio. All 3 of these biological
products have the same active ingredient, called vedolizumab.
PB016 has not been administered to humans before. The purpose of this study is
to investigate how quickly and to what extent PB016 is absorbed and eliminated
from the body compared to the EU-approved Entyvio, and US-approved Entyvio. It
will also be investigated how the body responds to PB016 compared to the two
Entyvio products. In addition, the study will assess the safety and
tolerability profiles of PB016 and both Entyvio products.
Study design
For the study it is necessary that the volunteer stays in the research center
for 1 period of 9 days (8 nights). This will be followed by 8 short visits to
the research center. These short visits will take place on Day 10, 15, 29, 43,
64, 85, 106, and 127.
Day 1 is the day when the volunteer receives the study compound. The volunteer
is expected at the research center the day before the day of administration of
the study compound, and will leave the research center on Day 8 of the study.
Below is an overview of the days of stay at the research center, or when the
volunteers visits the research center.
Screening: Day -28 up to Day 2 ; Arrival on Day -1; In-house stay: Day -1 up to
Day 8
Departure: Day 8; Short visits on Days 10, 15, 29, 43, 64, 85, 106, and 127;
Follow-up on Day 127
Intervention
The planned dose levels for the study are as follows:
The (up to) 120 volunteers will receive one of three treatments on Day 1 once:
27 to 40 : PB016, intravenous infusion, 300 mg
27 to 40: EU-approved Entyvio, intravenous infusion, 300 mg
27 to 40: US-licensed Entyvio, intravenous infusion, 300 mg
Study burden and risks
Blood draw
Drawing blood may be painful or cause some bruising. The use of the indwelling
cannula can sometimes lead to inflammation, swelling, hardening of the vein,
blood clotting, and bleeding in the environment of the puncture site. In some
individuals, a blood draw can sometimes cause pallor, nausea, sweating, low
heart rate, or drop in blood pressure with dizziness or fainting.
In total, we will take about 286 milliliters (mL) for males and 296.5 mL for
females of blood from screening to follow up. This difference in blood volume
can be attributed from extra blood samples for pregnancy tests. This amount
does not cause any problems in adults. To compare: a blood donation involves
500 mL of blood being taken each time. If the investigator thinks it is
necessary for the safety of a participant, extra samples might be taken for
possible additional testing. If this happens, the total amount of blood drawn
may be more than the amount indicated above.
Heart tracing
To make a heart tracing, electrodes will be placed on arms, chest and legs.
Prolonged use of these electrodes can cause skin irritation.
Coronavirus test
Samples for the coronavirus test will be taken from the back of the nose and
throat using swabs. Taking the samples only takes a few seconds, but can cause
discomfort and can give an unpleasant feeling. Taking a sample from the back of
the throat may cause the volunteer to gag. When the sample is taken from the
back of the nose, the volunteer may experience a stinging sensation and the
eyes may become watery.
Trzy Lipy 3
Gdask 80-172
PL
Trzy Lipy 3
Gdask 80-172
PL
Listed location countries
Age
Inclusion criteria
1. Sex: male or female.
2. Age: 18 years to 65 years, inclusive, at screening.
3. Body mass index (BMI): 18.5 kg/m2 to 30.0 kg/m2, inclusive, at screening.
4. Status: healthy subjects.
5. The subject is healthy at screening as determined by their medical history,
physical examination, vital signs, an ECG, and clinical laboratory testing as
judged by the Investigator.
Further criteria apply
Exclusion criteria
1. Any known prior exposure to vedolizumab or any other therapeutic mAb or any
other B- and T-cell targeting therapies provided with biological drugs 4 months
before study.
2. Any known exposure to immunosuppressive or immunomodulatory synthetic drugs
or other synthetic drugs with known immunosuppressive or immunomodulatory
action (eg, methotrexate, cyclosporine, azathioprine, mitoxantrone, tacrolimus)
within 3 months before study.
3. Known or suspected hypersensitivity to vedolizumab, or any components of the
formulation used (citric acid monohydrate, sodium citrate dihydrate,
L-histidine, L histidine monohydrochloride, larginine hydrochloride,
polysorbate 80).
4. Any exposure to steroids within one month prior to dosing, to agents such as
interferon-β, glatiramer acetate, fingolimod, or laquinimod within the last 2
months, to teriflunomide during the last 3.5 months, or to dimethyl fumarate
within 6 months prior to dosing.
5. Plasma exchange within 3 weeks prior to dosing.
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 | EUCTR2021-003594-57-NL |
| CCMO | NL81326.056.22 |