Study IM011-127 is a Phase 2 randomized, double-blind, placebo-controlled, multicenter clinical study designed to assess the safety and tolerability, efficacy and biomarker response of BMS-986165 12 mg BID in subjects with moderate to severe…
ID
Source
Brief title
Condition
- Gastrointestinal ulceration and perforation
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of the study is to estimate the efficacy of BMS-986165 at
Week 12
This will measured by the proportion of subjects in clinical response at Week
12
Secondary outcome
Secondary objectives of the study will be as follows:
1. to assess the safety and tolerability of BMS-986165. This will be measured
by the Number and proportion of subjects experiencing Adverse Events (AE),
Serious AEs, AEs leading to discontinuation from the study, and AEs of interest
(AEI) throughout the study
2. to estimate the effect of BMS-986165 on inflammatory biomarkers. This will
be measured by the change in baseline in biomarkers of inflammation over time.
3. To explore the efficacy of BMS-986165 at Week 12. This will be measured by:
i. Proportion of subjects in clinical remission at Week 12
ii. Change from baseline in modified Mayo score at Week 12
iii. Change from baseline in individual subscores of the modified Mayo score at
Week 12
iv. Change from baseline in the UC-100 score at Week 12
4. To explore the efficacy of BMS-986165 over time. This will be measured by:
i. Change from baseline in the Stool Frequency (SF) and Rectal Bleeding (RB)
subscores at over time
ii. Change from baseline in the sum of the SF and RB subscores over time
iii. Proportion of participants in symptomatic remission over time
iv. Change from baseline in partial Mayo score over time
5. To explore the effect of BMS-986165 on the endoscopic appearance of the
mucosa. This will be measured by:
i. Change from baseline in the UC Endoscopic Index of Severity (UCEIS) score at
Week 12
Ii. Proportion of subjects in endoscopic remission at Week 12
Iii. Proportion of subjects in endoscopic improvement at Week 12
Iv. Proportion of subjects with endoscopic response at Week 12
6. To explore the effect of BMS-986165 on the histological appearance of the
mucosa. This will be measured by:
i. Change from baseline in the Robarts Histopathology Index (RHI) at Week 12
Ii. Proportion of subjects in histologic improvement by Geboes score
7. To explore the efficacy of BMS-986165 at Week 52. This will be measured by:
i. Proportion of subjects in clinical remission at Week 52
Ii. Proportion of subjects in clinical response at Week 52
Iii. Proportion of subjects in endoscopic remission at Week 52
Iv. Proportion of subjects with endoscopic improvement at Week 52
v. Proportion of subjects with histologic improvement at Week 52.
vi. Proportion of subjects with corticosteroid-free remission at Week 52.
8. To estimate the effect of BMS-986165 on inflammatory biomarkers. This will
be measured by a change in baseline in biomarkers of inflammation over time.
9. To explore the effect of BMS-986165 on peripheral blood (PB) immune cells.
This will be measured by a change from baseline in PB immune cells over time.
10. To explore the effect of BMS-986165 on mucosal cells. This will be measured
by a change from baseline in mucosal cells at week 12.
11. To explore the effect of BMS-986165 on the intestinal microbiome in stool
and colon mucosa. This will be measured by a change from baseline in the
intestinal microbiome over time.
12. To explore the effect of BMS-986165 on the metabolome in stool and serum.
This will be measured by a change from baseline in metabolome over time.
13. To explore the effect of BMS-986165 on the transcriptome in blood and colon
biopsies. This will be measured by a change from baseline in gene expression.
14. To explore the effect of BMS-986165 on the epigenetics in PB immune cells
and colon biopsies. This will be measured by a change from baseline in
epigenetics.
15. To explore the PK of BMS-986165. This will be measured by comparing
concentrations of BMS-986165, BMT-153261, and other metabolites (if applicable)
at various timepoints.
16. To explore the effect of BMS-986165 on PROs and quality of life. This will
be measured by a change from baseline at various timepoints for the
inflammatory bowel disease questionnaire (IBDQ).
17. To explore the effect of BMS-986165 on UC-related hospitalization and
surgery. This will be measured by the proportion of subjects with surgery
and/or hospitalisation due to UC at various time points.
Background summary
IM011-127 is a multicentre, phase 2, double-blind study involving patients with
moderate to severe Ulcerative Colitis (UC). The study will assess the safety
and efficacy of BMS-986165 at two dose levels (6mg and 12mg), compared with
placebo. The placebo arm is included in this study design to mitigate bias in
the reporting of safety data and patient reported outcomes. Previous research
and pharmacology data models show that greater target engagement may be
achieved when the dose is increased from 6mg twice daily (BID).
UC is a chronic inflammatory disease of the gastrointestinal tract which has an
impact on mortality and quality of life. The management and treatment of the
disease has placed a huge demand on various healthcare services. Despite new
treatment options which have become available over the last several years,
significant challenges remain. Current treatments are often ineffective, only
inducing are temporary response. In other cases the treatment regimens can
cause toxic side effects. There is still remains a significant need for
well-tolerated and effective treatments. For example, studies with tumour
necrosis factor inhibitors (TNFi) report that 10% to 30% of subjects do not
respond to their first treatment and 23% to 46% of subjects lose their response
over time. Therefore, there is still an unmet need for novel, safe,
well-tolerated, and orally administered therapies that can effectively treat UC
and modify the disease course.
BMS-986165 is a selective Tyrosine Kinase 2 (TyK2) inhibitor. TyK2 is an
enzyme involved in various signalling pathways found within the cell known as
cytokines: interlukin (IL)-12, IL-23 and Type I interferon (IFN) signalling.
The TyK2 enzyme works by speeding up the transfer of phosphate groups from
high-energy, phosphate-donating molecules to specific proteins. This process is
known as phosphorylation. The phosphorylation of these proteins results in the
downstream activation of specific responses for these signalling pathways.
TyK2 is widely expressed. TYk2-dependent signalling pathways and the chemical
messengers that they modulate are thought to be involved in the onset and
development of various immune-mediated diseases including UC, Crohn's disease
(CD), psoriasis, psoriatic arthritis and systemic lupus erythematous (SLE).
Data from this study will be analysed to:
(i) estimate the efficacy of BMS-986165 12 mg twice daily in patients with
moderate to severe UC;
(ii) evaluate the safety and tolerability of BMS-986165 in that patient
population;
(iii) estimate the effect of BMS-986165 on biomarkers (signalling factors in
the blood) of inflammation;
(iv) explore if biomarkers are associated with a clinical response to
BMS-986165 or are predictive of clinical response;
(v) determine if biomarkers should be further studied in the Phase 3 clinical
trial program;
Study objective
Study IM011-127 is a Phase 2 randomized, double-blind, placebo-controlled,
multicenter clinical study designed to assess the safety and tolerability,
efficacy and biomarker response of BMS-986165 12 mg BID in subjects with
moderate to severe Ulcerative Colitis. The primary objective is to estimate the
effect of BMS-986165 on clinical response at Week 12.
Study design
Study IM011-127 is a multicenter, randomized, double-blind, placebo-controlled,
parallel group, Phase 2 clinical trial designed to assess the safety and
tolerability, efficacy, and biomarker response of BMS-986165 12 mg twice daily,
orally following a 12-week treatment period. An additional 40-week Open Label
Extension (OLE) period (to Week 52) is available for eligible subjects.
Approximately 50 patients will participate in the study, with 10 expected to
take part from the Netherlands
The study is divided into a screening period, 2 treatment periods and a
follow-up period. The first treatment period will be double-blind. The
effectiveness of the study treatment will be compared to the effectiveness of a
placebo. Patients will be assigned by chance to one of two treatment groups:
• Group 1: BMS-986165 12 mg twice a day, or
• Group 2: Placebo twice a day.
Patients must be randomised within 14 calendar days of the screening endoscopy
assessment. Randomisation will be done by an automated sorting process through
IVRS (a telephone based computer system). This maintains the integrity of the
randomisation itself. To be eligible for randomisation patients must meet the
inclusion criteria and must not meet any of the exclusion criteria. Patients
will be expected to complete an electronic diary throughout the screening
period. The diary will be reviewed by the hospital research team to calculate a
Mayo score. This will contribute to the eligibility assessment.
There is an 75% chance the patient will receive BMS-986165 and a 25% chance of
receiving placebo. This double-blind treatment period will last up to 12
weeks.
The second treatment period will be open-label. Patients will receive BMS
986165 6 mg twice a day. This open-label extension treatment period will last
up to 40 weeks.
After patients have completed the treatment period or for those who permanently
discontinue the study drug before the end of the treatment period, they will
enter a 4 week post treatment follow-up period.
Intervention
Patients who have completed screening procedures (up to 28 days duration) and
met inclusion/exclusion criteria will be randomized on Day 1 of the treatment
period.
Patients will be randomized in a 3:1:1 ratio using interactive response
technology (IRT) to one of three arms:
Arm A (Treatment arm)
oral BMS-986165 12 mg, twice daily
Arm C (Control arm)
BMS-986165 placebo, twice daily
Patients in all arms will undergo the same study evaluation procedures:
assessments of medical and Ulcerative Colitis (UC) disease history, prior
medications, concomitant medications and UC medications, tobacco use, baseline
Stool Frequency; blood, stool and urine collection for checking safety,
pharmacokinetics, and biomarkers, vital signs monitoring, endoscopy with
biopsies, ECG, additional efficacy assessments and the physician*s global
assessment (PGA); and patient collection of PROs in daily electronic diaries.
After patients complete the first treatment period, they may be eligible to
enter the Open-label Extension Period: Subjects who are likely to derive a
clinical benefit from ongoing participation in the study following Week 12, as
judged by the investigator, are eligible to enter the OLE period and receive
the following study treatment:
BMS-986165 6 mg BID
Patients who complete the Week 12 visit and decline to enter the OLE period,
those who complete the Week 52 visit, or those who permanently discontinue
study drug at any time during the study (Section 7) will enter a 4-week
post-treatment follow-up period.
Study burden and risks
Several sources of research suggest that inhibition of TYK 2 signalling by
BMS-986165 may be beneficial to patients with active Ulcerative Colitis (UC).
Study IM0111-27 is the first study involving patients with moderate to severe
UC, receiving BMS-986165 at doses above 6 mg BID PO. The BMS-986165 12 mg BID
treatment regimen has not been studied previously in UC patients. Therefore the
study has been designed to closely monitor patients safety throughout. Safety
monitoring will occur at study sites, by the Sponsor, and also by an external,
independent Data Monitoring.
Adverse Events of Interest (AEIs) have been defined, based on the mechanism of
action of BMS-986165 and the observed safety profile in the BMS-986165 clinical
trial program. The eligibility and randomisation criteria have been clearly
defined to ensure that subjects have *failed* at least 1 first-line standard of
care medication (ie, had a primary nonresponse, secondary loss of response, or
intolerance), have active UC on randomisation, and also to minimize the risk
for AEIs such as infections or malignancy, which may be associated with
immunomodulator use. Frequent study visits and safety assessments, with
monitoring of subject safety by investigators, the Sponsor, and the Data
Monitoring Committee are designed to promote the safety of subjects within this
study. In addition, the protocol provides clear recommendations on the
recognition and management of AEs that have been observed with BMS-986165 12 mg
BID in completed Normal Healthy Volunteer studies.
Medical Monitoring by the Sponsor
Patient safety will be monitored in a blinded manner by the Sponsor on a
regular basis. The Sponsor will review blinded patient-level data entered in
the clinical database as well as aggregated safety data across studies. This
approach facilitates close monitoring of individual safety events as well as
surveillance for potential safety signals.
Data Monitoring Committee (DMC)
An external, independent DMC will provide oversight on the safety of patients
within this study, The DMC will regularly review accumulating data from this
study, and advise the Sponsor regarding the continuing safety of trial subjects
and those yet to be recruited to the trial, as well as the continuing validity
and scientific merit of the trial.
Data summaries and listings will be provided to the DMC to facilitate their
safety assessment at regularly scheduled meetings and on an ad-hoc basis if
needed. The DMC will also be provided with suspected, unexpected serious
adverse reaction (SUSAR) reports relating to BMS-986165 and recommendations
from other DMCs supporting the BMS-986165 clinical development program.
Regular DMC safety reviews will include all AEs, SAEs, and AEIs. Based on their
review of safety data, the DMC will make recommendations regarding the
appropriateness of continuing the study, with or without study modifications,
or stopping the study.
In addition to regularly scheduled DMC meetings, ad hoc DMC meetings will occur
in the following circumstances:
- Two or more subjects experience an SAE of the same preferred term and that
is considered related to the study treatment by the investigator (for example,
not explained by intercurrent medical condition or concomitant medication)
- Two or more subjects are discontinued due to the same laboratory abnormality
as defined in section 7.1 in the protocol
As part of the trial, patients will be expected to attend multiple clinic
visits where they will undergo physical examinations, vital sign measurements,
endoscopy, biopsy, ECG, blood, stool and urine tests for safety assessment,
pregnancy testing (for females of child bearing potential) and monitoring for
adverse events. Blood will also be collected at certain visits for research
purposes (Pharmacokinetic and biomarker studies).
Patients will be asked to complete an electronic diary about their stool
frequency and any occurrence of rectal bleeding, daily, throughout the
screening and treatment periods. They will also be required to complete
questionnaires about their ulcerative colitis disease and quality of life and
various points throughout the study.
Patients will be required to take tablets twice daily for up to 52 weeks,
during the treatment period. The diary and pill bottle will be reviewed by
site-staff. Study treatment may be taken without regard to meals. Patients are
required to fast for a minimum of 10 hours before the randomization visit (Day
1) and the Week 12 (Day 85) visit, as fasting lipid and glucose blood samples
will be obtained at those times.
Women of child-bearing potential must agree to follow instructions for methods
of contraception for the duration of treatment with the study medicine.
BMS-986165 could provide clinical benefit and improvements in the outcomes for
patients with UC. However, with all experimental drugs and clinical trials,
there are known and unknown risks. Study medication and procedure related risks
are outlined in the patient information sheet in detail to ensure the patients
are fully informed before agreeing to participate.
Orteliuslaan 1000
Urecht 3528 BD
NL
Orteliuslaan 1000
Urecht 3528 BD
NL
Listed location countries
Age
Inclusion criteria
1.) Type of Participant and Target Disease Characteristics
a. A diagnosis of Ulcerative Colitis (UC) at least (>=) 3 months* duration prior
to screening and source documents must include (i) an endoscopy report, which
shows features consistent with UC, and (ii) a histopathology report showing
features consistent with UC.
If an endoscopy report is not available prior to screening, the screening
endoscopy can be used to confirm the diagnosis. If a histopathology report is
not available prior to screening, endoscopic biopsies can be obtained at the
screening endoscopy (with appropriate consent) and sent to a local
histopathology laboratory for reporting, to meet the criteria described above
prior to randomization.
b. UC disease distribution extending proximal to the rectum (ie, left-sided
colitis or pancolitis)
c. Moderately to severely active UC, defined by a modified Mayo score of 5 to 9
points inclusive, which includes all of the following:
i. A stool frequency (SF) subscore of >= 2, and
ii. A rectal bleeding (RB) subscore >= 1, and
iii. An endoscopic (ES) subscore of >= 2
d. Must be up to date with surveillance for dysplasia and screening for
colorectal neoplasia, according to local standard of care
2.) Age and Reproductive Status
a. Males and Females, ages 18 (or local age of majority) to 65 years,
inclusive, at the time of screening.
b. Women who are not of child-bearing potential are exempt from contraception
requirements. Female subjects must have documented proof that they are not of
childbearing potential
c. Women of Child Bearing Potential (WOCBP) must have a negative highly
sensitive serum or urine pregnancy test.
(minimum sensitivity 25 IU/L or equivalent units of human chorionic
gonadotropin) within 24 hours prior to the start of study treatment. If a urine
test cannot be confirmed as negative (eg, an ambiguous result), a serum
pregnancy test is required. The participant must be excluded from participation
if the serum pregnancy result is positive.
d. A female subject is eligible to participate if she is not pregnant or
breastfeeding and at least one of the following conditions applies:
(1) Is not a WOCBP
OR
(2) a WOCBP and using a contraceptive method(s) as described in the protocol
during the intervention period (at a minimum until after the last dose of study
intervention)
e. Males who are sexually active with WOCBP must agree to follow instructions
for contraception as desribed in the protocol
f. Azoospermic males are exempt from contraceptive requirements
3. ) Prior UC Medication Failure Inclusion Criteria
a. Documentation of an inadequate response, loss of response, or intolerance to
a treatment course of 1 or more of the following standard of care medications:
i. Oral 5-aminosalicylic acids (5-ASAs) (eg, mesalamine, sulfasalazine,
olsalazine, or balsalazide)
ii. Corticosteroids (eg, prednisone or budesonide MMX)
iii. Immunomodulators (eg, azathioprine [AZA], 6-mercaptopurine [6-MP], or
methotrexate [MTX]
iv. Anti-TNF agents (eg, infliximab, adalimumab, or golimumab)
v. Integrin inhibitors (eg, vedolizumab)
vi. Anti-IL-12/IL-23p40 antibodies (eg, ustekinumab): subjects can only be
included if they were intolerant to treatment. Inadequate response or loss of
response is an exclusion factor.
4.) Washout and Dose Stabilization Inclusion Criteria
a. Must comply with washout periods for prohibited concomitant medications
summarized in the protocol
b. Must comply with dose stabilization rules for 5-ASAs, corticosteroids and
probiotics (if applicable) prior to randomization, as listed in the protocol
Exclusion criteria
1.) Medical Conditions
a. Women who are pregnant or breastfeeding
2.) Ulcerative Colitis (UC) Exclusion Criteria
a. UC involving the rectum only (UC proctitis).
b. Current diagnosis of Crohn*s disease, indeterminate colitis, ischemic
colitis or microscopic.
c. Current or recent (within 12 weeks prior to randomization) evidence of
fulminant UC (also known as acute severe UC) or toxic megacolon.
d. Current or recent (within 12 weeks prior to randomization) evidence of
bowel perforation or intra-abdominal abscess.
e. Current or recent colonic diverticulitis. Subject must be adequately
treated and off antibiotics for diverticulitis for 60 days prior to
randomization.
f. Current colonic adenomas or mucosal dysplasia
i. A subject with adenomatous polyps may be eligible if the polyps have been
completely removed or eradicated (documented). The subject must be free of
polyps at randomization.
ii. A subject with mucosal dysplasia may be eligible if the dysplasia has been
completely removed/resected/eradicated (as applicable, documented), and the
subject is free of dysplasia at randomization. This should be discussed with
the BMS Medical Monitor/designee prior to screening
iii. Subjects with a history of UC greater than (>) 8 years* duration (who have
not had a colonoscopy in the prior 12 months) must have a full colonoscopy at
screening.
Subjects who require a colonoscopy to screen for dysplasia (based on local
guidelines) must have a full colonoscopy at screening
Subjects who require a colonoscopy to screen for colorectal cancer (based on
local guidelines) must have a full colonoscopy at screening.
3.) Gastrointestinal (GI) Surgery Exclusion Criteria
a. History or evidence of extensive colonic resection, subtotal or total
colectomy, with or without a stoma or pouch.
b. Current need for, or anticipated need for, surgical intervention for UC
during the study.
c. GI surgery within 3 months prior to randomization Subject must have adequate
wound healing prior to randomization.
4.) Additional Gastrointestinal (GI) Exclusion Criteria
a. Current or recent (within 12 weeks prior to randomization) GI disease that
may confound efficacy assessment or any GI disease associated with poor
absorption of the investigational product (for example, untreated celiac sprue,
bile salt-mediated diarrhoea, or short bowel syndrome).
b. Receiving enteral feeding, defined formula diets, or total parenteral
alimentation.
5.) Immune and Infectious Disease Exclusion Criteria
a. History of congenital or acquired immunodeficiency
b. Known serious infection, defined as any infection requiring hospitalization
or treatment with parenteral (intramuscular [IM] or IV) antimicrobial agents
(eg, antibiotics, antiviral, antifungal, or antiparasitic agents) within 30
days of the first dose of study treatment. Completion of oral antimicrobial
agents within 2 weeks of the first dose of study treatment.
Antibiotics used to cover a procedure such as endoscopy would not exclude the
subject.
c. Current or recent (within 12 weeks prior to randomization) herpes zoster,
herpes simplex, or influenza infection
d. History of disseminated or complicated herpes zoster infection (including,
but not limited to, multi-dermatomal involvement, ophthalmic zoster, central
nervous system involvement, or post-herpetic neuralgia)
6.) Prior Concomitant/ Therapy
a. Prior exposure to BMS-986165 or a TYK2 inhibitor
b. Prior treatment failure (inadequate response or loss of response) to
medications that target the same pathway as BMS-986165, such as anti-
IL-12/IL-23p40 antibodies (eg, ustekinumab, briakinumab) or anti-IL-23p19
antibodies (eg, guselkumab, risankizumab, tildrakizumab, brazikumab [MEDI2070],
and mirikizumab [LY3074828]).
Subjects who have been exposed to the medications listed above, but who have
not had a treatment failure, may be eligible for inclusion. Similarly, subjects
who have experienced intolerance to the medications listed above (eg, an
infusion reaction) without a treatment failure may be eligible for inclusion.
c. Prior treatment failure (inadequate response or loss of response) to a JAK
inhibitor, such as tofacitinib
Prior exposure to a JAK inhibitor, without treatment failure, is not
exclusionary.
d. Current oral prednisone > 20 mg/day (or equivalent) or current budesonide
MMX > 9 mg/day (or equivalent)
e. Use of topical rectal treatment with 5-ASA or corticosteroid within 2 weeks
prior to randomisation
f. Use of intravenous (IV) corticosteroids within 2 weeks prior to the
screening period
g. Use of immunomodulators (AZA, 6-MP, or MTX) within 4 weeks prior to
randomization
h. Use of other investigational agents within 4 weeks or 5 half-lives
(whichever is longer) prior to randomization
Faecal transplant is considered an investigational agent for the purpose of
this protocol and is subject to a 4-week washout period prior to randomization.
i. Previous stem cell transplantation
j. Use of lymphocyte apheresis or selective monocyte, granulocyte apheresis
(eg, Cellsorba*) within 12 months prior to randomization
k. Administration of a live vaccine within 90 days prior to randomization
Live vaccines should not be used during the study or within the 2 months
following last dose.
Heat-killed, or otherwise inactivated vaccines, or protein or subunit vaccines
(eg, influenza and pneumococcal vaccines) may be received at any time on study.
The efficacy of vaccination in subjects who are receiving BMS-986165 is unknown.
l. Currently on any therapy for chronic infection (eg, pneumocystis,
cytomegalovirus, herpes simplex, herpes zoster, invasive bacterial or fungal
infections, or atypical mycobacteria)
7.) Physical and Laboratory Test Findings
a. Evidence of organ dysfunction or any clinically significant deviation from
normal in physical examination, vital signs, ECG, CXR, or clinical laboratory
determinations beyond what is consistent with the target population
b. Clinically significant abnormalities on Chest Xray (CXR) or ECG
c. Evidence of active or latent tuberculosis (TB), as follows:
i. History of active TB prior to the screening visit, regardless of completion
of adequate treatment
OR
ii. Has signs or symptoms of active TB as judged by the investigator OR CXR
obtained during the screening period or anytime within 6 months before
screening, with documentation, with evidence of current active or old active
pulmonary TB
OR
iii. Latent TB infection (LTBI) defined as positive IFN-γ release assay (IGRA)
such as QuantiFERON®-TB Gold, QuantiFERON®-TB Gold Plus, or T-Spot® at
screening, or other diagnostic test in the absence of clinical manifestations
OR
iv. An indeterminate IGRA result at screening with no signs or symptoms of
active TB
Subjects diagnosed with LTBI during screening may be eligible if (1) there are
no current signs or symptoms of active TB and (2) the subject has received
adequate documented treatment for LTBI within 5 years of screening OR has
initiated prophylactic treatment for LTBI per local guidelines. The subject
must now be rescreened after 1 month of treatment. The subject must agree to
complete a locally recommended course of treatment for LTBI to continue in the
study.
A subject with an indeterminate IGRA test result may be retested within the
same screening period. If the second result is also indeterminate, the subject
will be excluded from the study. If the second result is positive, the subject
should be treated as having LTBI. If the second result is negative, the subject
may be eligible provided no other exclusion criterion for TB is met.
d. Evidence of hepatitis B virus (HBV) at screening as defined in the protocol
e. Evidence of hepatitis C virus (HCV) at screening, defined as:
i. Positive for HCV antibody (anti-HCV) and
ii. Positive via a confirmatory test for HCV (eg, detectable
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
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 | EUCTR2019-004878-26-NL |
| CCMO | NL75314.018.20 |