A Phase 2A, Exploratory, Two-Part, Open-Lable Trial to Evaluate Dose and Safety of Nanoecho PARTICLE-1 (Ferumoxtran) Using Nanoecho Imaging Device Examinations of Rectal Lymph Nodes in Healthy Volunteers (Part a) and Rectal Cancer Patients (Part B).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

NanoEcho AB (publ)

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Not possible to specify, Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

16 Oct 2024 → ongoing

Decision date (initial)

2024-09-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Safety

Part A1: To identify sufficient dose of NEP-01 and timepoint for examination of rectal lymph nodes in healthy volunteers using NanoEcho Imaging Device.
Part A2: To validate dose of NEP-01 and timepoint for using NanoEcho Imaging Device for examination of healthy rectal lymph nodes in healthy volunteers.
Part B: To validate dose of NEP-01 and timepoint for using NanoEcho Imaging Device for examination of healthy rectal lymph nodes in rectal cancer patients.

Secondary objectives 12

1. Part A: To evaluate lymph node detection using NEP-01 and NanoEcho Imaging Device for examination of rectal lymph nodes in healthy volunteers.
2. Part A: To evaluate the safety and tolerability of NEP-01 and NanoEcho Imaging Device examination in healthy volunteers.
3. Part A: To evaluate the usability of the NanoEcho Imaging system in healthy volunteers.
4. Part B: To evaluate lymph node detection using NEP-01 and NanoEcho Imaging Device for examination of rectal lymph nodes in rectal cancer patients.
5. Part B: To evaluate suspectedlymph node detection using NanoEcho Imaging Device, MRI, and histopathology.
6. Part B: To evaluate lymph node metastasis detection of NEP-01 using NanoEcho Imaging Device in rectal cancer patients.
7. Part B: To evaluate the safety and tolerability of NEP-01 and NanoEcho Imaging Device examination in rectal cancer patients.
8. Part B: To evaluate the usability of the NanoEcho Imaging system in rectal cancer patients.
9. Part A2: To evaluate lymph node detection using NEP-01 and NanoEcho Imaging Device for examination of rectal lymph nodes in healthy volunteers.
10. Part A2: To evaluate the different probe covers used.
11. Part A2: To evaluate the safety and tolerability of NEP-01 and NanoEcho Imaging Device examination in healthy volunteers.
12. Part B: To validate dose of NEP-01 and timepoint for using NanoEcho Imaging Device for examination of unhealthy rectal lymph nodes in rectal cancer patients.

Conditions and MedDRA coding

Rectal cancer

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Part A: Willing and able to give written informed consent for participation in the trial.
2. Part A: Healthy male participant, or female participant of non-childbearing potential aged 18 to 50 years, inclusive.
3. Part A: Body mass index (BMI) ≥ 18.5 and ≤ 30.0 kg/m2 at the time of the screening visit.
4. Part A: Medically healthy participant without abnormal clinically significant medical history, physical findings, vital signs, ECG and laboratory values at the time of the screening visit, as judged by the Investigator. (Discussion is encouraged between the Investigator and the Sponsor Medical Representative regarding the clinical relevance of any abnormal laboratory value during the pre dose period.)
5. Part A: Women of non-childbearing potential are pre-menopausal females who have undergone any of the following surgical procedures; hysterectomy, bilateral salpingectomy or bilateral oophorectomy, or who are post-menopausal defined as 12 months of amenorrhea (in questionable cases a blood sample with detection of follicle stimulating hormone [FSH] >25 IU/L is confirmatory). Male participants must be willing to use condom or be vasectomised or practice sexual abstinence from heterosexual intercourse (only allowed when this is the preferred and usual lifestyle of the participant) to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the administration of IMP until 3 months after the administration of IMP. Any female partner of a non-vasectomised male participant who is of childbearing potential must use contraceptive methods with a failure rate of < 1% to prevent pregnancy (see above) from at least 2 weeks prior to the administration of IMP to 4 weeks after the administration of IMP.
6. Part B: Willing and able to give written informed consent for participation in the trial.
7. Part B: Participant with primary rectal cancer planned for surgery. MRI must have been performed within the last 3 months before administration of IMP.
8. Part B: Tumour diagnosed with stage T1-T4.
9. Part B: It should be possible to use a probe in rectum (no tumour that blocks).
10. Part B: Male participant, or female participant of non-childbearing potential ≥ 18 years of age.
11. Part B: Women of non-childbearing potential are pre-menopausal females who have undergone any of the following surgical procedures; hysterectomy, bilateral salpingectomy or bilateral oophorectomy, or who are post-menopausal defined as 12 months of amenorrhea (in questionable cases a blood sample with detection of FSH >25 IU/L is confirmatory). Male participants must be willing to use condom or be vasectomised or practice sexual abstinence from heterosexual intercourse (only allowed when this is the preferred and usual lifestyle of the participant) to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the administration of IMP until 3 months after the administration of IMP. Any female partner of a non-vasectomised male participant who is of childbearing potential must use contraceptive methods with a failure rate of < 1% to prevent pregnancy (see above) from at least 2 weeks prior to the administration of IMP to 4 weeks after the administration of IMP.

Exclusion criteria 31

1. Part A: History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial, or influence the results or the participant’s ability to participate in the trial.
2. Part A: Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the administration of IMP.
3. Part A: Malignancy within the past 5 years, with the exception of in situ removal of basal cell carcinoma.
4. Part A: Any planned major surgery within the duration of the trial.
5. Part A: Any previous or current anorectal disorder which may increase risk or burden of trial participation.
6. Part A: Any positive result at the screening visit for serum hepatitis B surface antigen, hepatitis C antibodies and/or human immunodeficiency virus (HIV).
7. Part A: After 10 minutes supine rest at the screening visit, any vital signs values outside the following ranges: - Systolic blood pressure: <90 or ≥140 mmHg, or - Diastolic blood pressure <50 or ≥90 mmHg, or - Pulse <40 or ≥90 bpm
8. Parat A: Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the screening visit, as judged by the Investigator.
9. Part A: History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to the IMP, IMP excipients or other parenteral iron products, or excipients of the enema to be used in the trial.
10. Part A: Person with pacemaker.
11. Part A: Person with metal implants.
12. Part A: Previous history of full radiation of rectum.
13. Part A: Regular use of any prescribed or non-prescribed medications, including antacids, analgesics, herbal remedies, vitamins and minerals, within 2 weeks prior to the (first) administration of IMP, except occasional intake of paracetamol (maximum 2000 mg/day and not exceeding 3000 mg/week), as well as nasal decongestants without cortisone, antihistamine or anticholinergics for a maximum of 10 days, at the discretion of the Investigator.
14. Part A: Planned treatment or treatment with another investigational drug within 3 months prior to Day -1. Participants consented and screened but not dosed in previous phase I trials are not to be excluded.
15. Part A: Current smokers or users of nicotine products. Irregular use of nicotine (e.g., smoking, snuffing, chewing tobacco) less than three times/week is allowed before the screening visit.
16. Part A: Positive screening result for drugs of abuse or alcohol at the screening visit or on admission to the trial site prior to the (first) administration of the IMP. (Positive results that are expected given the participant’s medical history and prescribed medications can be disregarded as judged by the Investigator.)
17. Part A: History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
18. Part A: Presence or history of drug abuse, as judged by the Investigator.
19. Part A: History of, or current use of anabolic steroids, as judged by the Investigator.
20. Part A: The Investigator considers the participant unlikely to comply with trial procedures, restrictions and requirements.
21. Part B: History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial, or influence the results or the participant’s ability to participate in the trial.
22. Part B: Person with any kind of stoma.
23. Part B: Person with pacemaker or implantable cardioverter defibrillators.
24. Part B: Person with magnetic implants in the middle part of their body.
25. Part B: Previous history of radiation of rectum.
26. Part B: Prescence of malignancy other than rectal cancer.
27. Part B: After 10 minutes supine rest at the screening visit, abnormal clinically significant systolic blood pressure, diastolic blood pressure or pulse, as judged by the Investigator.
28. Part B: MRI examination and analysis planned within eight weeks after Visit 2.
29. Part B: History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to the IMP, IMP excipients or other parenteral iron products.
30. Part B: Planned treatment or treatment with another investigational drug within 3 months prior to Day -1. Participants consented and screened but not dosed in previous phase I trials are not to be excluded.
31. Part B: The Investigator considers the participant unlikely to comply with trial procedures, restrictions and requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 10

1. Part A1: - Dose-response curve (normalised average nTrace value for lymph nodes with an even nTrace distribution))
2. Part A1: - Time -response curve (normalised average nTrace value for lymph nodes with an even nTrace distribution)
3. Part B: Normalised average nTrace value (in healthy lymph nodes with an even nTrace distribution) corresponding to dose and time selection in Part A.
4. Part A1: Dose-response curve (normalised average nTrace value for lymph nodes regardless of nTrace distribution)
5. Part A1: Time -response curve (normalised average nTrace value for lymph nodes regardless of nTrace distribution)
6. Part A2: Dose-response curve (normalised average nTrace value for lymph nodes with an even nTrace distribution) corresponding to dose and time selection in Part A1
7. Part A2: Time -response curve (normalised average nTrace value for lymph nodes with an even nTrace distribution) corresponding to dose and time selection in Part A1.
8. Part A2: Dose-response curve (normalised average nTrace value for lymph nodes regardless of nTrace distribution) corresponding to dose and time selection in Part A1.
9. Part A2: Time -response curve (normalised average nTrace value for lymph nodes regardless of nTrace distribution) corresponding to dose and time selection in Part A1.
10. Part B: Normalised average nTrace value (in healthy lymph nodes regardless of nTrace distribution) corresponding to dose and time selection in Part A.

Secondary endpoints 28

1. Part A1: At what size of lymph nodes and in which sections and fractions are lymph nodes detectable (B-mode), but no nTrace detectable in lymph nodes?
2. Part A1: At what size of lymph nodes and in which sections and fractions are nTrace detectable in lymph nodes?
3. Part A1: At what size of lymph nodes and in which sections and fractions are nTrace showing an even distribution in lymph nodes?
4. Part A1: Frequency, seriousness, and intensity of adverse events (AEs).
5. Part A1: Frequency and nature of device deficiencies (DDs).
6. Part A1: Clinically significant changes in vital signs, ECG, safety laboratory measurements (haematology, clinical chemistry, coagulation) and physical examination findings.
7. Part A1: Result of user experience questionnaire
8. Part B:At what size of lymph nodes and in which sections and fractions are lymph nodes detectable (B-mode) but no nTrace detectable in lymph nodes?
9. Part B: At what size of lymph nodes and in which sections and fractions are nTrace detectable in lymph nodes?
10. Part B: At what size of lymph nodes and in which sections and fractions are nTrace showing an even distribution in lymph nodes?
11. Part B: Number of suspected lymph nodes detected by NanoEcho diagnostic method, historic MRI and pathology.
12. Part B: True positive fraction (N+) (sensitivity) and true negative fraction (N0) (specificity) of identified lymph nodes as assessed by NEP-01 using NanoEcho Imaging Device in rectum using histopathology as true comparator.
13. Part B: Size of detectable lymph node with metastases
14. Part B: Size of detectable metastases.
15. Part B: How far off from the tumour is tumour infiltration detectable?
16. Part B: Frequency, seriousness and intensity of AEs.
17. Part B: Frequency and nature of DDs.
18. Part B: Clinically significant changes in vital signs, ECG, safety laboratory measurements (haematology, clinical chemistry, coagulation) and physical examination findings.
19. Part B: Result of user experience questionnaire.
20. Part A2: At what size of lymph nodes and in which sections and fractions are lymph nodes detectable (B-mode), but no nTrace detectable in lymph nodes?
21. Part A2: At what size of lymph nodes and in which sections and fractions are nTrace detectable in lymph nodes?
22. Part A2: At what size of lymph nodes and in which sections and fractions are nTrace showing an even distribution in lymph nodes?
23. Part A2: Identify which probe cover that gives the best visualised images and highest nTrace value.
24. Part A2: Frequency, seriousness, and intensity of adverse events (AEs) for the IMP and the medical device.
25. Part A2: Frequency and nature of device deficiencies (DDs).
26. Part A2: Clinically significant changes in vital signs, ECG, safety laboratory measurements (haematology, clinical chemistry, coagulation) and physical examination findings.
27. Part B: To compare the proportion of lymph nodes with an even distribution and the normalised nTrace value in unhealthy nodes compared to healthy nodes.
28. Part B: Normalised average nTrace value (in unhealthy lymph nodes regardless of nTrace distribution) corresponding to dose and time selection in Part A.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

NanoEcho AB (publ)

Sponsor organisation

NanoEcho AB (publ)

Address

Gasverksgatan 1, St Peters Kloster St Peters Kloster

City

Lund

Postcode

222 29

Country

Sweden

Scientific contact point

Organisation

NanoEcho AB (publ)

Contact name

Ulrika Axelsson

Public contact point

Organisation

NanoEcho AB (publ)

Contact name

Ulrika Axelsson

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications