The purpose of this study is to investigate how safe the new compound JNJ-67670187 is and how well it is tolerated when it is administered to healthy volunteers. Another purpose is to see how the body responds to JNJ 67670187 by analysing blood,…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the safety and tolerability of JNJ-67670187 (11-strain Clostridia
mix) compared with placebo after administration of:
Single Dose administered orally once in healthy participants (Part 1).
Multiple Dose administered orally once daily over 14 consecutive days with and
without bowel preparation pretreatments in healthy participants (Parts 2 and
3).
Secondary outcome
To assess the colonization dynamics of JNJ-67670187 in the stool following
single and multiple oral study intervention administrations (Parts 1 and 2).
To assess the colonization dynamics of JNJ-67670187 following multiple oral
study intervention administrations with specific pretreatments (Parts 2 and 3).
Background summary
JNJ-67670187 is a new compound that may eventually be used for the treatment of
inflammatory bowel disease (IBD).
JNJ 67670187 contains 11 viable bacterium (Clostridium) strains which were
isolated from the faeces of a single healthy human donor. These bacteria do not
cause illnesses and produce no toxins. Similar bacterial strains have been
demonstrated to reduce inflammation in laboratory experiments. JNJ 67670187,
which is a so-called live biotherapeutic product (LBP), may provide a
therapeutic benefit for patients with IBD. JNJ-67670187 is in development and
is not yet registered as a drug.
Study objective
The purpose of this study is to investigate how safe the new compound
JNJ-67670187 is and how well it is tolerated when it is administered to healthy
volunteers. Another purpose is to see how the body responds to JNJ 67670187 by
analysing blood, urine, saliva, and feces samples.
This study will be performed in 102 to 144 healthy volunteers, divided over 3
parts. In Part 1 of this study, JNJ 67670187 will be administered to humans for
the first time. This part will run in Belgium and has been approved by the IEC
and HA. In this part, 18 healthy volunteers will receive JNJ 67670187 as a
single dose at 2 different dose levels. In Parts 2 and 3, JNJ 67670187 will be
taken multiple days (14 days) at the same dose levels. The remainder of this
document concerns Part 2 / Part 3 only.
In Part 2, another purpose is to evaluate the effect of pre-treatment with an
antibiotic on the growth of the bacteria from JNJ 67670187 in the bowel.
Therefore, volunteers with and without pre-treatment with an antibiotic will be
compared.
The results of Part 2 of the study are expected to allow a well-informed
decision on whether to continue with the development of JNJ 67670187 for
treatment of IBD and whether to include a pre-treatment with antibiotics in
future studies with JNJ 67670187 or in future therapy for IBD patients.
Part 2 will consist of 4 groups of 14 volunteers each.
In Part 3, another purpose is to find out if pre-treatment with a laxative, or
with an antibiotic together with a laxative, will help the bacteria in JNJ
67670187 to grow in the bowel of the body.
The results of Part 3 of the study are expected to allow a well-informed
decision on whether to continue with the development of JNJ 67670187 for
treatment of IBD and also whether to include a pre-treatment with laxative with
or without antibiotic in future studies with JNJ-67670187 or in future therapy
for IBD patients.
Part 3 of study will consist of up to 2 groups and 1 optional group of 14
volunteers each.
Study design
Group 1: 7 days (6 nights) with an amount of ambulatory visits. On day 1 the
subjects will receive one oral capsule of study medication or placebo.(This
part is performed in Belgium and has been approved by the HA/IEC).
Group 2: 7 days (6 nights) with an amount of ambulatory visits. On day one the
subjects will receive 10 oral capsules of study medication or placebo.(This
part is performed in Belgium and has been approved by the HA/IEC).
Group 3: 19 days (18 nights). Admission to clinic on day -2. Days 1-14 the
subjects will receive an oral capsule with study medication once a day.
Group 4: 24 days (23 nights). Admission to clinic on day -7 for baseline
assesments. Pre-treatment will start on day -6. On days -6 to -2 the subjects
will receive 1 vancomycine capsule four times a day. On days 1-14 the subjects
will receive an oral capsule with study medication once a day.
Group 5: 19 days (18 nights). Admission to clinic on day -2. On days 1-14 the
subjects will receive 10 capsules of study medication once a day.
Group 6: 24 days (23 nights). Admission to clinic on day -7 for baseline
assessments. Pre-treatment will start on day -6. On days -6 to -2 the subjects
will receive 1 vancomycine capsule once a day. On days 1-14 the subjects will
receive 10 capsules of study medication once a day.
Group 7: 20 days (19 nights). Admission to clinic on day -3 for baseline
assesments. Pre-treatment will start on day -2. On days -6 to -2 the subjects
will receive 17g PEG laxative with 240mL of juice or water 4 times a day. On
days 1-14 the subjects will receive 10 capsules of study medication once a day.
Group 8: 24 days (23 nights) Admission to clinic on day -7 for baseline
assessments. Pre-treatment will start on day -6. On days -6 to -3 the subjects
will receive one capsule with vancomycin four times a day. On days -2 they will
receive one capsule of vancomycine four times a day and 17mg PEG laxative with
240
mL juice or water once a day. On days 1-14 they will receive 10 capsules of
study medication once a day.
Group 9: 19 days (18 nights). Admission to clinic on day -2. On days 1-14 the
subjects will receive 10 capsules of study medication once a day. On day 15 a
liquid injection will be inserted in the intestine as a preparation for the
biopsy.
Intervention
You will receive JNJ-67670187 or placebo once daily for 14 days as oral
capsules with 240 milliliters (mL) of water. JNJ-67670187 will be given at 2
different dose levels, which means that you may receive either 1 capsule or 10
capsules.
In Group 1 and 2 the subjects will receive the study medication once. In group
1 one capsule will be administered. In group 2 ten capsules will be
administered.
In Groups 3 and 5, volunteers will only receive the study compound without any
pre-treatment. In Group 5, the strength of the study compound will be higher
than in Group 3. Therefore, Group 5 will only start when it is confirmed that
safety results of the first 18 days of Group 3 do not raise any safety issues.
Volunteers in Groups 4 and 6 will receive pre treatment with an antibiotic
(i.e., vancomycin) for 5 days, followed by one day without any treatment before
administration of the study compound will be started. The antibiotic will be
given 4 times a day at an oral dose of 125 mg / dose for 5 consecutive days. In
Group 6, the strength of the study compound will be 10 times higher compared
to Group 4.
Group 7 is an optional group which will only be conducted if in previous
parts/groups no bacteria from JNJ 67670187 were detected in the feces of the
volunteers. Volunteers in Group 7 will be pre treated with a laxative (i.e.,
Movicolon) for 2 days before administration of the study compound. The laxative
will be a polyethylene glycol (PEG) laxative given 4 times a day for 2 days at
a dose of 17 grams mixed with approximately 240 mL of water or juice.
Volunteers in Group 8 will be pre treated with an antibiotic (i.e., vancomycin)
for 5 days in combination with 2 days of pre treatment with a laxative (i.e.,
Movicolon), before administration of the study compound .
• The antibiotic vancomycin will be given 4 times a day at an oral dose of 125
mg / dose for 5 consecutive days.
• The laxative will be a polyethylene glycol (PEG) laxative given 4 times a day
for 2 days at a dose of 17 grams mixed with approximately 30 240 mL of water or
juice.
The 2 day pre treatment with the laxative will be started on the last (5th) day
of pre treatment with the antibiotic.
Group 9 is an optional group which will only be conducted if in previous
parts/groups no bacteria from JNJ 67670187 were detected in the feces of the
volunteers. The purpose of Group 9 would then be to find out if bacteria from
JNJ 67670187 will populate the mucous wall of the bowel. This will be
investigated by taking small tissue biopsy and mucous samples of the bowel.
Depending on results in previous groups in Parts 2 and 3, pre treatments may be
added to this group.
Part 3 will begin after safety and tolerability of the higher dose of JNJ
67670187 are assessed in previous groups in Part 2. As the dose of JNJ 67670187
will be the same in Groups 7 and 8 (i.e., 10 capsules), these groups may be
dosed simultaneously.
Study burden and risks
Pre-treatment (if applicable)
Symptoms associated with vancomycin use could include: dropping blood pressure,
shortness of breath, redness of the upper body and/or face, and decrease in
kidney function (in less than 1 out of 10 people) and transient or permanent
hearing loss (in less than 1 out of 100 people). The risk of side effects from
vancomycin is expected to be very low during the 5-day period of dosing because
the duration of use is shorter than prescribed for a true infection so that the
amount of drug taken is not likely to remain in the body for a long period of
time.
Laxative(group 7 en 8)
Common side effects include: abdominal cramps, bloating, gassiness, flatulence,
burping, and nausea. Rare symptoms associated with Movicolon use could include:
vomiting, dehydration, allergic reactions. The risk of side effects from
Movicolon is expected to be very low at the doses and for the length of
treatment prescribed in this study. Although the risk in healthy adults is very
low, to prevent dehydration from occurring during the time you take Movicolon
the subjects will be encouraged to drink extra fluids during the day.
Procedures
Drawing blood and/or insertion of the indwelling cannula may be painful or
cause some bruising.
In total, we will take no more than 500 milliliters (mL) of blood from you.
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 your arms, chest and legs. Prolonged use of these
electrodes can cause skin irritation (rash and itching).
Biopsy
Serious complications such as a perforation (a hole in the wall of the colon)
are rare (less than 1 out of 1000 people) and could require surgery. The
procedure may be associated with abdominal pain, diarrhea, bleeding,
flatulence, anal pain and bloating but even these occur in just 1-2% of the
procedures.
Turnhoutseweg 30
Beerse 2340
BE
Turnhoutseweg 30
Beerse 2340
BE
Listed location countries
Age
Inclusion criteria
1. Be a male or female.
2. Be 18 (or the legal age of consent in the jurisdiction in which the study is
taking place) to 60 years of age, inclusive.
3. Have a body mass index (BMI) between 18 and 30 kilogram per square metre
(kg/m^2) inclusive, and a body weight of at least 50 kilogram (kg).
4. Be otherwise healthy on the basis of physical examination, medical history,
and vital signs, and 12-lead electrocardiogram (ECG) performed at screening and
at admission.
5. Be otherwise healthy on the basis of clinical laboratory tests performed at
screening and at admission. If the results of the serum chemistry panel,
hematology, or urinalysis are outside the normal reference ranges, the
participant may be included only if the investigator judges the abnormalities
or deviations from normal to be not clinically significant. This determination
must be recorded in the participant's source documents and initialed by the
investigator.
Exclusion criteria
Coexisting Medical Conditions or Past Medical History
1. History of any clinically significant medical illness or medical disorders
the investigator considers should exclude the participant, including (but not
limited to), neuromuscular, hematological disease, immune deficiency state,
respiratory disease, hepatic or gastrointestinal (GI) disease, neurological or
psychiatric disease, ophthalmological disorders, neoplastic disease, renal or
urinary tract diseases, or dermatological disease.
2. Has any condition for which, in the opinion of the investigator,
participation would not be in the best interest of the participant (eg,
compromise the well being) or that could prevent, limit, or confound the
protocol-specified assessments.
3. Inability to swallow capsules (dysphagia).
4. Has a known intolerance or allergy to vancomycin, polyethylene glycol (PEG)
laxatives, or any of the excipients in the study interventions.
5. Has a known intolerance or allergy to 2 or more classes of the antibiotics
that may be used to treat infection with the study intervention (tigecycline,
metronidazole, ampicillin/sulbactam, amoxicillin/clavulanate, meropenem,
imipenem/cilastatin, and/or vancomycin).
Design
Recruitment
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 | EUCTR2018-002287-81-NL |
| ClinicalTrials.gov | NCT03723746 |
| CCMO | NL67899.056.18 |