The study will be performed in 2 parts, Part 1 and Part 2. Part 2 has been clinically completed. The remainder of this document concerns Part 1 only. The purpose of Part 1 of this study is to determine the reversal of the blood thinning effects of…
ID
Source
Brief title
Condition
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the reversal of the anticoagulant effects of JNJ-70033093 by 4F-PCC
and rFVIIa in healthy subjects as measured by changes from baseline of the
coagulation testing parameters (aPTT and TGA).
Secondary outcome
To assess the safety and tolerability of 4F-PCC and rFVIIa when
co-administered with milvexian to reverse its anticoagulant effects in healthy
participants.
To assess the pharmacokinetics (PK) of multiple doses of milvexian at 200 mg
BID on Days 4 to 7 (Part 1).
To assess the pharmacokinetics (PK) of single 100 mg and 500 mg doses of
milvexian administered under fed condition on Day 1 in healthy participants
(Part 2).
To assess the PK of rFVIIa in healthy participants (Part 2).
Background summary
Milvexian is a new compound that may potentially be used for the treatment of
blood clots in the heart, in the blood vessels or in the brain. Milvexian is a
blood thinner (an anti coagulant) that can prevent the formation of blood clots
in blood vessels (so-called *thrombo-embolic* disorders). These blood clots can
travel through the bloodstream and block arteries which prevents blood from
delivering oxygen and nutrients to the organs. When that happens in the heart,
it is called a heart attack and, in the brain, it is called a cerebral
infarction (also called stroke). All these conditions may ultimately result in
death or permanent disability. Milvexian aims to prevent the formation of the
blood clot. It works by blocking a *blood clotting* protein (FXIa) from
performing its function. Anticoagulation of all types have the potential to
contribute to bleeding. In addition, there may be situations in which the
anticoagulation effects may need to be reversed (eg, urgent surgery).
Therefore, the availability of a drug that can reverse the effects of milvexian
could be valuable in patients with life-threatening bleeding or in those
requiring urgent surgery.
The drug that is used in this part of the study (Part 1) to reverse the effects
of milvexian is 4F PCC. 4F PCC is available on the market as Kcentra, Beriplex,
Cofact, and Octaplex. It contains 4 factors that act as *coagulants* that make
blood clot again.
Study objective
The study will be performed in 2 parts, Part 1 and Part 2. Part 2 has been
clinically completed. The remainder of this document concerns Part 1 only.
The purpose of Part 1 of this study is to determine the reversal of the blood
thinning effects of milvexian (also called JNJ 70033093). To reverse the blood
thinning effects we will test the blood clotting medicine 4F-PCC. We will
determine the reversal by measuring different proteins in your blood that
influence blood clotting (this is called pharmacodynamics). Milvexian has been
administered to humans before. It has also been extensively tested in the
laboratory and on animals. Milvexian will be tested as multiple doses of 200 mg
twice daily for 3.5 days. 4F-PCC is no new drug; it is already available on the
market in several dosages and formulations. 4F-PCC will be tested as a single
intravenous infusion at a dose of 50 IU/kg. The reversal effects of 4F-PCC will
be compared to the effects of a placebo. A placebo is a medicine without any
active ingredient.
Additionally, we will investigate how safe and well tolerated the new compound
milvexian is when co administered with 4F-PCC to healthy volunteers. It will
also be investigated how quickly and to what extent milvexian is absorbed and
eliminated from the body (this is called pharmacokinetics).
Part 1 of this study will be performed in approximately 16 healthy male and
female volunteers. Part 1 has 2 periods, Period 1 and Period 2. In each study
Period, milvexian and 4F-PCC or its matching placebo will be tested. There will
be an interval of 14 to 21 days between the two study periods.
Study design
Participation from screening until the follow-up visit will be approximately
116 days.
On Day 1, 2, and 3 of each period, milvexian will be given twice per day: once
in the morning and once in the evening (12 hours apart). On Day 4 of each
period, only a morning dose will be given. Milvexian will be given as oral
capsules with 240 milliliters (mL) of noncarbonated water. The dose of
milvexian that will be given each time is 200 milligram (mg). This will be
given as 2 capsules of 100 mg each.
After fasting for 10 hours overnight on Day 1, 2, and 3 of each period, the
volunteer will be given a standard breakfast 30 minutes before the morning dose
of milvexian. the volunteer is asked to eat the entire breakfast within 20
minutes.
On Day 4 of each period, milvexian will be given without a breakfast after
fasting for 10 hours overnight.
4 hours after ingestion of milvexian on Day 4, 4F-PCC or placebo will be given
as an intravenous infusion (solution of the compound that will be administered
directly in a blood vessel) over up to approximately 30 minutes.
There are 2 treatments in this study:
- Treatment A: 200 mg milvexian twice daily on Days 1 to 3 and a morning dose
on Day 4 and intravenous infusion of 50 IU/kg* 4F-PCC on Day 4 only
- Treatment B: 200 mg milvexian twice daily on Days 1 to 3 and a morning dose
on Day 4 and an intravenous infusion of placebo on Day 4 only
* This means that 50 IU of 4F-PCC will be administered per 1 kg of body weight,
so the actual dose will depend on the volunteers body weight.
The volunteer will receive both Treatment A and B (one treatment in each
period). The order in which the volunteer will receive Treatment A or Treatment
B in each period will be determined by drawing lots.
The actual study will consist of 2 periods during each the volunteer will stay
in the research center for 8 days (7 nights).
In total, the volunteer will visit the research center 4 times:
• The screening visit
• 2 visits of 8 days during each treatment period
• The follow-up visit
Additionally, there will be a follow-up phone call after leaving the research
center in the second period.
There will be at least 14 days but no more than 21 days between Day 1 of each
study period.
Intervention
See Study design
Study burden and risks
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. Insertion of a needle that delivers the
reversal drug 4F-PCC to a vein in your arm may cause pain, bleeding, bruising
or infection at the place where the needle goes into the skin.
In total, we will take approximately 500 milliliters (mL) of blood from the
volunteer from screening to follow-up visit, including the blood samples taken
to repeat tests for safety assessments. This amount does not cause any problems
in adults. To compare: a blood donation involves 500 mL of blood being taken at
once each time. Sometimes a blood test may need to be repeated. If this happens
the total amount of blood drawn will be more than this.
To make a heart tracing, electrodes (small, plastic patches) will be pasted at
specific locations on the volunteers arms, chest and legs. Prolonged use of
these electrodes can cause skin irritation (rash and itching).
A sample for the coronavirus test will be taken from the back of the volunteers
nose and 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 the volunteers throat may cause the volunteer to gag. When the
sample is taken from the back of the volunteers nose, the volunteer may
experience a stinging sensation and the volunteers eyes may become watery.
Turnhoutseweg 30
Beerse B-2340
BE
Turnhoutseweg 30
Beerse B-2340
BE
Listed location countries
Age
Inclusion criteria
1. Participants must be male or female between 18 and <55 years of age.
2. Participants must be healthy on the basis of medical history, physical
examination, vital signs, ECG, and laboratory test results.
3. If a woman, must have a negative highly sensitive serum (β-human chorionic
gonadotropin [β-hCG]) pregnancy test at screening and urine (β-hCG) pregnancy
test on Day -1 of each study period (Part 1) or on Day -1 of Period 1 (Part 2).
4. Body mass index (weight [kg]/height^2 [m]^2) >=18.0 and <29.9 kg/m^2 body
weight not less than 50 kg and not more than 100 kg.
5. After being supine for 5 minutes, systolic blood pressure between 90 and 140
mmHg, inclusive; and no higher than 90 mmHg diastolic, inclusive.
For a complete overview see the protocol
Exclusion criteria
1. If a woman, pregnant, breast-feeding or planning to become pregnant during
the study.
2. History or family history of any known illness that, in the opinion of the
investigator, might confound the results of the study or pose an additional
risk in administering study intervention to the subject or that could prevent,
limit or confound the protocol specified assessments.
3. Participants with current hepatitis B infection, or hepatitis C infection,
or human immunodeficiency virus type1 (HIV-1) or HIV-2 infection at study
screening.
4. History of any significant drug allergy (such as anaphylaxis or
hepatotoxicity) and known allergy to the study intervention or any of the
excipients of the formulations. History of allergy to or unwillingness to
consume any component of high-fat breakfast menu to be provided in this study.
5. Any of the following laboratory results outside of the ranges specified
below at screening or on Day -1 of Period 1, confirmed by repeat: a. Hemoglobin
or hematocrit < lower limit of normal
b. Platelet count < lower limit of normal c. aPTT, or PT > ULN d. Low-density
lipoprotein (LDL), High-density lipoprotein (HDL), apolipoprotein B, or
lipoprotein a, outside the normal reference ranges
(at the screening visit only)
For a complete overview 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 | EUCTR2020-000180-24-NL |
| CCMO | NL73369.056.20 |