This study has been transitioned to CTIS with ID 2023-509334-19-00 check the CTIS register for the current data. This study aims to determine the safety, pharmacokinetics (PK) and recommended Phase 3 dose (RP3D) of RYZ101 in Part 1, and the safety,…
ID
Source
Brief title
Condition
- Endocrine neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Efficacy
To determine if treatment with RYZ101, compared to SoC therapy, improves
centrally confirmed PFS in study subjects.
PFS as determined by BICR
PFS will be defined as the time from the date of randomization until the date
of progression (as determined by BICR from tumor assessments using RECIST v1.1)
or death due to any cause, whichever occurs earlier.
Secondary outcome
Secondary Efficacy
To determine if treatment with RYZ101, compared to SoC therapy, improves OS in
study subjects.
OS: OS will be defined as the time from the date of randomization until the
date of death due to any cause.
To determine if treatment with RYZ101, compared to SoC therapy, improves ORR in
study subjects.
ORR, as determined by BICR according to RECIST v1.1.
To evaluate the efficacy of RYZ101 compared to SoC therapy in terms of
Investigator-assessed PFS.
PFS as determined by the Investigator
To further evaluate the efficacy of RYZ101 compared to SoC therapy by
Investigator-assessed ORR, as well as BOR, DoR, and disease control rate as
determined by BICR and by the Investigator.
- ORR, as assessed by the Investigator according to RECIST v1.1
- BOR, disease control rate (PR + CR + SD), and DoR (only for subjects with a
RECIST v.1.1 response) assessed by BICR and by the Investigator according to
RECIST v1.1
Safety
Objectives Endpoints
To characterize the safety and tolerability of RYZ101 in study subjects
Incidence and severity of AEs by NCI CTCAE v5, including SAEs, laboratory
changes, ECG changes, and other safety findings
Exploratory
To evaluate the efficacy of RYZ101 compared to SoC therapy in terms of
investigator-assessed PFS after first subsequent anti-cancer therapy (PFS2)
PFS2 as determined by the investigator
PFS2 will be defined as the time from randomization to second objective disease
progression, or death from any cause, whichever first
To evaluate biomarkers and their potential association with the efficacy and
safety of RYZ101
Relationship between biomarkers, including but not limited to CgA in the serum
and (5-HIAA) in the urine, with AEs of special interest and/or efficacy
endpoints (e.g., PFS, OS, BOR, DoR)
To study the evolution and determinants of subjects* HRQoL
Changes in
- EQ-5D-5L
- EORTC QLQ-C30 and
- EORTC QLQ GI NET21 questionnaire scores.
Pharmacokinetic
To evaluate the PK of RYZ101 **Population predicted exposure parameters (i.e.
Cmax, AUC, average concentration)
- Relationship between exposure endpoints and clinical outcomes (efficacy and
safety)
Pharmacokinetic and ECG Substudy
To evaluate PK and ECG parameters in a subset of approximately 30 subjects
- PK parameters, measured by:
- Cmax, Tmax, AUC, Vd, clearance, T1/2
- Percentage of radioactivity of the injected parent drug recovered in urine
- ECG parameters (including QTc), measured by continuous ECG recording using a
12-lead Holter monitoring device
Background summary
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a group of
biologically and clinically heterogeneous and relatively indolent neoplasms
arising in secretory cells of the neuroendocrine system located in the
gastrointestinal (GI) tract (GI-NETs) and pancreas (p-NETs) (Cives and
Strosberg, 2018; Cives et al. 2020).
GEP-NETs are life-threatening tumors that are often associated with
debilitating hormonal symptoms. The only curative treatment for subjects with
GEP-NET is surgical resection; however, only a minority of subjects present
early enough for complete surgical resection; see Section 2.1
for details.
Part 2 will evaluate the safety and efficacy of RYZ101 compared with
investigator-selected SoC therapy in subjects with inoperable, advanced,
well-differentiated SSTR+ GEP-NETs that have progressed following treatment
with 177Lu-SSA.
Study objective
This study has been transitioned to CTIS with ID 2023-509334-19-00 check the CTIS register for the current data.
This study aims to determine the safety, pharmacokinetics (PK) and recommended
Phase 3 dose (RP3D) of RYZ101 in Part 1, and the safety, efficacy, and PK of
RYZ101 compared with investigator-selected standard of care (SoC) therapy in
Part 2 in subjects with inoperable, advanced, well-differentiated, somatostatin
receptor expressing (SSTR+) gastroenteropancreatic neuroendocrine tumors
(GEP-NETs) that have progressed following treatment with Lutetium 177-labelled
somatostatin analogue (177Lu-SSA) therapy, such as 177Lu-DOTATATE or
177Lu-DOTATOC (177Lu-DOTATATE/TOC), or 177Lu-high affinity [HA]-DOTATATE.
The aim of the PK and electrocardiogram (ECG) substudy is to evaluate the PK
and cardiac safety of RYZ101 in a subset of subjects randomized to RYZ101 in
Part 2 of the study.
Study design
This is a global, multicenter, randomized, open-label, 2-part (Part 1 [Phase
1b] followed by Part 2 [Phase 3]) study of RYZ101, an Actinium 225 radiolabeled
somatostatin analog (SSA) for injection. Part 1 is an uncontrolled dose
de-escalation study to confirm the safety and determine the RP3D of RYZ101
based on Bayesian optimal interval (BOIN) design (Liu and Yuan 2015;
Yuan et al. 2016) with a target toxicity rate of 25%. The initial dose will be
consistent with the dose range evaluated in the pilot study by Ballal, Bal, and
colleagues (Ballal et al. 2020; Bal et al. 2021). The purpose of the
randomized, controlled Phase 3 evaluation is to evaluate the progression-free
survival (PFS) benefits of RYZ101 over SoC therapy in subjects with SSTR+
GEP-NET that has progressed following treatment with 177Lu-SSA.
Part 2 is a randomized, controlled Phase 3 study to determine if treatment with
RYZ101 prolongs PFS assessed by blinded independent central review (BICR)
(primary objective), and overall survival (OS; key secondary objective)
compared to SoC therapy in subjects with SSTR+ GEP-NETs that have progressed
following treatment with 177Lu-SSA. Approximately, 210 subjects will be
randomized in a balanced 1:1 ratio to receive RYZ101 administered at the RP3D
once Q8W for up to 4 cycles or to protocol-permitted SoC therapy (selected by
the Investigator prior to randomization) given according to local labeling; see
Figure 1-2. Randomization will be stratified by length of time between the last
dose of 177Lu-SSA and first disease progression following this treatment (<12
months vs. >=12 months), by anatomic location of the primary tumor
(gastrointestinal [GI] tract vs. pancreas) and by treatment with long-acting
SSA (octreotide 20-30 mg every 4 weeks [Q4W] or lanreotide 120 mg Q4W) at
baseline that will continue on study (yes vs. no).
Subjects with a body weight of <=45 kg will receive RYZ101 at a dose calculated
based on a minimum body weight of 45 kg. This is based on clinical experience
with 5 patients under 50 kg treated with 225Ac-DOTATATE (Bal et al. 2021; Data
on File).
During the treatment period, subjects will undergo radiographical evaluations
(by local computed tomography [CT]/ magnetic resonance imaging [MRI]) every 12
weeks ±7 days from the date of first dose of study treatment (regardless of
drug interruption) until the time of centrally confirmed disease progression
(PD). Disease progression and tumor response will be evaluated by BICR and by
the investigator using Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1 (Eisenhauer et al.2009). Subjects should remain on their assigned
treatment until central confirmation of PD. Management of the subject will be
based on the investigator*s assessment of the disease. Subjects who discontinue
study drug for radiographic PD confirmed by BICR will be followed approximately
every 6 months (via phone or office visit) during LTFU until the end of the
study for survival status, adverse events (AEs)/serious adverse events (SAEs)
considered to be related to study treatment, adverse events of special interest
(AESIs), laboratory evaluations (may be completed locally), development of
secondary malignancy, and subsequent anticancer therapy information.
Additionally, subjects will continue CT/MRI scans every 12 weeks ± 7 days until
investigator-assessed radiographic progression after first subsequent
anticancer therapy. Subjects who discontinue study drug for reasons other than
PD confirmed by BICR or the start of subsequent anticancer therapy will
continue to have local CT/MRI assessments every 12 weeks ±7 days until
radiographic PD confirmed by BICR. Thereafter, these subjects will be followed
approximately every 6 months during LTFU for survival status, AEs/SAEs
considered related to study treatment, AESIs, laboratory evaluations (may be
completed locally), development of secondary malignancy, and use of subsequent
anticancer therapy until the end of the study. Additionally, subjects will
continue CT/MRI scans every 12 weeks ±7 days until investigator-assessed
radiographic progression after first subsequent anticancer therapy. Following
radiographic PD confirmed by BICR, subjects randomized to the SoC therapy group
may be eligible to cross over and receive RYZ101; these subjects will be
followed for safety and survival status, as well as for investigator-assessed
radiographic progression.
The EuroQol Group 5-Dimension Questionnaire, 5-level version (EQ-5D-5L), the
European Organization for Research and Treatment of Cancer (EORTC) core quality
of life questionnaire (EORTC QLQ-C30) and the EORTC quality of life
questionnaire for gastrointestinal neuroendocrine tumors (QLQ-GI-NET21) will be
used to evaluate subject health-related quality of life (HRQoL) in study
subjects in Part 2 randomized to the RYZ101 or SoC therapy arms. Quality of
life will not be evaluated for subjects in the SoC group if and after they
crossover to RYZ101.
An independent data monitoring committee (IDMC) will review safety and efficacy
data at the interim analyses. In addition, the IDMC will periodically review
safety data at regularly scheduled meetings, according to a prespecified IDMC
charter.
With the exception of subjects participating in the PK and ECG substudy (see
below), all subjects randomized to RYZ101 at select sites (sites with
capabilities and selected to perform the required PK analyses) will also
undergo sparse PK blood sample collection according to the schedule described
in Table 1-2.
Intervention
The estimated study duration will be approximately 7 years (estimated from
January 2022 to January 2029). In Part 2, subject follow-up will continue for 5
years after the last subject was randomized, or until a total of 130 deaths
have occurred, whichever occurs first.
RYZ101 will be supplied as a clear and colorless-to-slightly yellow solution in
a single-dose vial for intravenous (i.v.) infusion, administered Q8W, for a
total of 4 infusions. Detailed instructions for i.v. infusion of RYZ101 are
located in the Pharmacy Manual. Concomitant amino acids (containing arginine
and lysine) will be given with each RYZ101 administration for renal protection,
starting 30 minutes before the RYZ101 infusion for a total of at least 4 hours
in accordance with local practice and consistent with labeling. Instructions
for storage and handling of RYZ101, and co-administration of amino acids are
provided in the Pharmacy Manual.
Study burden and risks
What are the possible discomforts you may experience with checks or
measurements during the study?
- Blood sample: Taking a blood sample can be a little painful. Or you could get
a bruise as a result.
- Tumour biopsy: For patients who need to provide fresh tumour sample, the
risks include a brief sharp pain from the needle used to inject medicine to
numb the skin. The biopsy needle will produce a duller pain. There may be
bleeding, bruising, swelling, infection, or scarring at the site of the biopsy.
The location where the tumour sample is taken may require stitches which will
be removed by a study nurse or study doctor about one week after the biopsy.
The biopsy site should be kept covered, clean, and dry until it heals.
- Blood pressure: An inflatable cuff will be placed on your arm and a machine
will measure your blood pressure and heart rate, after you have been sitting
down for 5 minutes. You may experience mild discomfort in your arm while the
cuff is inflated.
- Computerized tomography (CT) scan: You will have to lie still on a table and,
at times, hold your breath for a few seconds in order to avoid blurring the
pictures. You may hear a slight buzzing, clicking and whirring sounds as the CT
scanner moves around your body. You will receive information on how to get
ready for this procedure. As part of the CT scans, contrast material may need
to be taken by mouth and/or injected into your vein to make certain organs and
tumour sites visible on the scan. This contrast material may cause an allergic
reaction or damage your kidneys.
- Multigated Acquisition Scan (MUGA): The radioactive tracer used during a MUGA
scan is a diagnostic dose of radiation that is similar to the dose you would
receive during a PET scan (described below). The radioactive substance you
receive is safe for most people. Your body will get rid of it through your
kidneys within about 24 hours.
- ECG: Small sticky pads are placed on your chest, shoulders and hips. These
may cause some local irritation and be uncomfortable to remove. We may also
need to clip small patches of your hair in these areas.
- MRI scan: An MRI scan is painless and will not expose you to X ray radiation.
Some people may feel frightened by the cramped space inside the machine or by
the loud, repeated sounds the machine makes. Because the MRI scan uses magnetic
field, you will be asked to remove all types of metal from your clothing and
all metal objects from your pockets. Please inform the study doctor if you have
metal in your body from an operation, e.g., heart pacemaker, artificial heart
valves, metal implants such as metal ear implants, bullet pieces, chemotherapy
or insulin pumps or any other metal such as metal clips or rings. The MRI
scanner makes loud banging noises while taking a measurement, so either ear
plugs, or specially designed headphones will be given to reduce the noise. MRI
scans are not usually recommended during pregnancy. During the MRI scan, you
will be asked to lie down on your back on a table and you will need to stay
still until the pictures have been taken. Each MRI examination should take less
than 1 hour. As part of the MRI scans, contrast material may need to be taken
by mouth and/or injected into your vein to make certain organs and tumour sites
visible on the scan. This contrast material may cause an allergic reaction or
damage your kidneys.
- PET scan: You will be given details of what to do to prepare for your PET
scan. For example, you will be asked not to eat for 4 to 6 hours before your
appointment time and to drink only water. You will be given an injection of a
small amount of a radiotracer (a radioactive substance injected in your body
prior to imaging that can be detected in your body by the scanner) into a vein
in your arm or hand. The radiotracer will travel to particular parts of your
body. By analysing the areas where the radiotracer does and doesn't build up,
it is possible to work out how well certain body functions are working and
identify any abnormalities. You will be asked to remain still for about an hour
before the scan (since moving and speaking can affect where the radiotracer
goes in your body) and also for about 30 minutes during the scan. You may hear
buzzing or clicking sounds during the scan. Risks include local pain, bruising,
bleeding, blood clot formation, and in rare instances, an infection might occur
at the site of where the needle is pricked for injecting the radiotracer. There
is a small risk of allergic reaction to the injected radiotracer.
You should not have close contact with pregnant women, babies and young
children for a few hours after this scan as you will be slightly radioactive
during this time.
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Listed location countries
Age
Inclusion criteria
1. Age of at least 18 years at the time of signing the informed consent.
2. Histologically proven, Grade 1-2 well differentiated, inoperable, advanced
GEP-NETs.
3. Ki67 (mitotic) index <=20%.
4. Eastern Cooperative Oncology Group (ECOG) status 0-2.
5. Life expectancy of at least 12 weeks.
6. Subjects with functional tumors who are receiving octreotide LAR or
lanreotide for symptom control must be on a stable dose for at least 12 weeks
prior to enrollment (Part 1) or randomization (Part 2).
a. Subjects with nonfunctional tumors or functional tumors that do not require
octreotide LAR or lanreotide for symptom control must discontinue octreotide
LAR or lanreotide at least 4 weeks prior to enrollment (Part 1) or
randomization (Part 2).
7. Progressive GEP-NET (GI or pancreas) based on RECIST v1.1 following a
minimum of 2 cycles and a maximum of 4 cycles of treatment with 177Lu-DOTATATE
(7.4 GBq ±10% each cycle or a total cumulative dose of up to 29.6 GBq ±10%),
177Lu-DOTATOC (7.5 GBq ±10% each cycle or a total cumulative dose of up to 30
GBq ±10%), or 177Lu-HA-DOTATATE (7.4 GBq ±10% each cycle or a total cumulative
dose of up to 29.6 GBq ±10%). Radiographic progression must be demonstrated
within 18 months from enrollment (Part 1) or randomization
(Part 2). Premature discontinuation of 177Lu-DOTATATE, 177Lu-DOTATOC, or
177Lu-HA- DOTATATE (i.e., 177Lu-SSA) treatment should not have been due to PD.
Dose reductions for
toxicity based on local labeling are allowed. No time limit is defined between
177Lu-SSA treatment and enrollment (Part 1)/randomization (Part 2). Other
anticancer treatments that do not meet exclusion criteria are allowed in this
interval. Subjects must have progressed on or after the last non-177Lu-SSA
anticancer treatment.
a. CT/MRI scan should be completed within 42 days (inclusive) prior to
enrollment (Part 1) or randomization (Part 2) and show disease progression
compared to a previous scan obtained at least 6 months following the last
177Lu-DOTATATE/TOC or 177Lu-HA- DOTATATE treatment (see Exclusion Criterion #1)
and within 18 months from screening (Figure 1-3). No non-SSA anticancer
treatment is permitted between the most recent scan used for eligibility
confirmation and the first dose of study treatment. A baseline CT/MRI scan must
always be obtained within 4 weeks (28 days) of the first dose of study
treatment for on-study response assessment (the most recent scan for
confirmation of progression may be used as the baseline scan if obtained prior
to enrollment/randomization and within 28 days of the first dose of study
treatment.)
b. For subjects on octreotide LAR or lanreotide, progression should be
documented while the subject was on a fixed dose of octreotide LAR or
lanreotide.
c. There must be at least 1 SSTR-PET imaging-positive (using a regulatory
agency-approved imaging method, e.g., 68Gallium [68Ga] or 64Copper
[64Cu]-based), measurable site of disease (according to RECIST v1.1) and no
RECIST v1.1 measurable metastatic lesions that are SSTR imaging -negative.
Assessment of SSTR expression must be within 90 days (inclusive) prior to
enrollment (Part 1) or randomization (Part 2) without any intervening non-SSA
anticancer treatments for GEP-NET.
d. Tumor uptake observed in each RECIST v1.1 measurable lesion using a
regulatory agency -approved SSTR-PET imaging method must be greater than the
liver uptake observed on regulatory agency-approved SSTR-PET imaging, to be
centrally confirmed in Part 2.
8. Part 2: Subject is a candidate for therapy with 1 of the following SoC
options:
a. Everolimus 10 mg daily by mouth
b. Sunitinib 37.5 mg daily by mouth
c. High-dose octreotide LAR 60 mg Q4W by intramuscular (i.m.) injection
d. High dose frequency lanreotide 120 mg every 2 weeks (Q2W) by deep
subcutaneous (s.c.) injection.
9. Adequate renal function, as evidenced by creatinine clearance (CrCl) >=50
mL/min (calculated using the Cockcroft-Gault formula)
10. Adequate hematologic function, defined by the following laboratory results:
a. Part 1: Hemoglobin concentration >=5.6 mmol/L (>=9.0 g/dL); absolute
neutrophil count (ANC) >=1500 cells/µL (>=1500 cells/mm3); platelets >=100 x 109/L
(100 x 103/mm3)
b. Part 2: Hemoglobin concentration >=5.0 mmol/L (>=8.0 g/dL); ANC >=1000 cells/µL
(>=1000 cells/mm3); platelets >100 x 109/L (100 x 103/mm3).
11. Total bilirubin <=3 x upper limit normal (ULN)
12. Serum albumin >=3.0 g/dL unless prothrombin time is within the normal range
13. For women of childbearing potential (WOCBP):
a. Negative serum pregnancy test within 48 hours prior to the first dose of
study treatment
b. Agreement to use barrier contraception and a second form of highly effective
contraception while receiving study treatment and for 6 months following their
last dose of study treatment. Alternatively, total
abstinence is also considered a highly effective contraception method when this
is in line with the preferred and usual lifestyle of the subject.
c. A woman is considered to be of childbearing potential if she is
postmenarchal, has not reached a postmenopausal state (>=12 continuous months of
amenorrhea with no identified cause other than menopause), and has not
undergone surgical sterilization (total hysterectomy, or bilateral tubal
ligation or bilateral oophorectomy at least 6 weeks before taking study
treatment).
14. Sexually active male subjects must use a condom during intercourse while
receiving study treatment and for 3 months after the last dose of the study
treatment and should not father a child during this period.
a. Male study participants whose sexual partners are WOCBP must also agree to
use a second form of highly effective contraception while receiving study
treatment and for 3 months following their last dose of RYZ101. Alternatively,
total abstinence is also considered a highly effective contraception method.
b. A condom is required to be used also by vasectomized men as well as during
intercourse with a male partner to prevent delivery of the drug via seminal
fluid.
Exclusion criteria
1. Subjects with a GEP-NET deemed nonresponsive to PRRT, defined as no disease
control (PR, CR, or SD) achieved for at least 6 months following the last dose
of prior 177Lu-DOTATATE/TOC or 177Lu-HA-DOTATATE treatment. 2. Known
hypersensitivity to 225Actinium, 68Gallium, 64Copper, octreotate, or any of the
excipients of DOTATATE imaging agents 3. Part 1: Prior treatment with
alkylating agents 4. Prior radioembolization 5. Any surgery, chemoembolization,
and radiofrequency ablation within 12 weeks prior to first dose of study drug
6. Use of anticancer agents within the following intervals prior to the first
dose of study drug: a. PRRT: within < 6 months (177Lu-DOTATATE/TOC or
177Lu-HA-DOTATATE only, as described in Inclusion Criterion #7) b.
Chemotherapy: within <6 weeks c. Small molecule inhibitors: within <4 weeks d.
Biological agents: within <7 days or <5 half-lives 7. Prior radiation therapy
as defined below: a. Part 1: Any prior external beam radiation therapy,
including stereotactic body radiation therapy (SBRT) b. Part 2: Any of the
following: i. Radiation therapy within 6 weeks prior to study enrollment ii.
Prior external beam radiation therapy to more than 25% of the bone marrow 8.
Prior participation in any interventional clinical study within 30 days prior
to first dose of study drug 9. Current somatic or psychiatric disease/condition
that may interfere with the objectives and assessments of the study 10.
Significant cardiovascular disease, such as New York Heart Association (NYHA)
Class >=II heart failure a. Subjects with a known left ventricular ejection
fraction (LVEF) <40% will be excluded. b. Subjects with known coronary artery
disease, congestive heart failure not meeting the above criteria, or LVEF <50%
must be on a stable medical regimen that is optimized in the opinion of the
treating physician. c. QT interval corrected for heart rate using Fridericia*s
formula (QTcF) >470 ms for females and >450 ms for males, demonstrated by the
average value of 3 consecutive ECGs 11. Resistant hypertension, defined as
persistent uncontrolled blood pressure (BP) >140/90 mmHg while on optimal doses
of at least 3 antihypertensive medications with 1 being a diuretic. Patients
with baseline hypertension may be eligible after initiation of antihypertensive
therapy. 12. Uncontrolled diabetes mellitus as defined by a persistent fasting
glucose >2 x ULN 13. Have a history of primary malignancy within the past 3
years other than (1) GEP-NET, (2) adequately treated carcinoma in situ or
non-melanoma carcinoma of the skin, (3) any other curatively treated malignancy
that is not expected to require treatment for recurrence during participation
in the study, or (4) an untreated cancer on active surveillance that may not
affect the subject*s survival status for >=3 years based on clinician
assessment/statement and with Medical Monitor approval. 14. Known brain,
meningeal or spinal cord metastases. In Part 2, subjects with previously
treated brain metastases will be allowed if the following conditions are met:
(a) there is no evidence of central nervous system (CNS) progression for at
least 6 months as assessed by local MRI for brain metastasis during screening;
(b) the subject has recovered from acute side effects of radiotherapy; and (c)
the subject is receiving a stable or decreasing dose of steroids. 15. For
subjects with functional tumors that require treatment with SSAs for symptom
control: a. Any subject receiving treatment with short-acting octreotide, which
cannot be interrupted for 24 hours before and 24 hours after the administration
of RYZ101. b. Any subject receiving treatment with octreotide LAR or
lanreotide, which cannot be interrupted for at least 4 weeks before the
administration of RYZ101. 16. Subject requires other treatment that in the
opinion of the investigator would be more appropriate than the therapy offered
in the study 18. Unable or unwilling to comply with the requirements of the
study protocol 19. PRRT other than 177Lu-DOTATATE/TOC or 177Lu-HA-DOTATATE as
described in Inclusion Criterion #7 20. Any condition requiring systemic
treatment with high-dose glucocorticoids (>=20 mg prednisone per day or
equivalent) within 14 days prior to first dose of study treatment and/or which
cannot be stopped while on study (unless solely for the purpose of adrenal
replacement). Inhaled or topical steroids and single dose of steroids as
pre-medication for CT scans with contrast are permitted.
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 |
|---|---|
| EU-CTR | CTIS2023-509334-19-00 |
| EudraCT | EUCTR2022-000507-12-NL |
| CCMO | NL81684.100.22 |