FERUMOXTRAN-10 for Rectal cancer

Inclusion criteria

• {"criterion_text":"- Part A: Willing and able to give written informed consent for participation in the trial.\n- Part B: Male participant, or female participant of non-childbearing potential ≥ 18 years of age.\n- Part A: Healthy male participant, or female participant of non-childbearing potential aged 18 to 50 years, inclusive.\n- Part A: Body mass index (BMI) ≥ 18.5 and ≤ 30.0 kg/m2 at the time of the screening visit.\n- 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.)\n- 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.\n- Part B: Willing and able to give written informed consent for participation in the trial.\n- Part B: Participant with primary rectal cancer planned for surgery. MRI must have been performed within the last 3 months before administration of IMP.\n- Part B: Tumour diagnosed with stage T1-T4.\n- Part B: It should be possible to use a probe in rectum (no tumour that blocks)."}

Exclusion criteria

• {"criterion_text":"- 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.\n- Part A: Person with pacemaker.\n- Part A: Person with metal implants.\n- Part A: Previous history of full radiation of rectum.\n- 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.\n- 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.\n- 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.\n- 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.)\n- Part A: History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.\n- Part A: Presence or history of drug abuse, as judged by the Investigator.\n- Part A: History of, or current use of anabolic steroids, as judged by the Investigator.\n- Part A: Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the administration of IMP.\n- Part A: The Investigator considers the participant unlikely to comply with trial procedures, restrictions and requirements.\n- 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.\n- Part B: Person with any kind of stoma.\n- Part B: Person with pacemaker or implantable cardioverter defibrillators.\n- Part B: Person with magnetic implants in the middle part of their body.\n- Part B: Previous history of radiation of rectum.\n- Part B: Prescence of malignancy other than rectal cancer.\n- 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.\n- Part B: MRI examination and analysis planned within eight weeks after Visit 2.\n- 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.\n- 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.\n- Part B: The Investigator considers the participant unlikely to comply with trial procedures, restrictions and requirements.\n- Part A: Any planned major surgery within the duration of the trial.\n- Part A: Any previous or current anorectal disorder which may increase risk or burden of trial participation.\n- Part A: Any positive result at the screening visit for serum hepatitis B surface antigen, hepatitis C antibodies and/or human immunodeficiency virus (HIV).\n- 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\n- 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.\n- 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."}

Primary endpoints

• {"endpoint_text":"- Part A1: - Dose-response curve (normalised average nTrace value for lymph nodes with an even nTrace distribution))","definition_or_measurement_approach":"Dose-response curve using normalised average nTrace value for lymph nodes with an even nTrace distribution"}
• {"endpoint_text":"- Part A1: - Time -response curve (normalised average nTrace value for lymph nodes with an even nTrace distribution)","definition_or_measurement_approach":"Time-response curve using normalised average nTrace value for lymph nodes with an even nTrace distribution"}
• {"endpoint_text":"- Part B: Normalised average nTrace value (in healthy lymph nodes with an even nTrace distribution) corresponding to dose and time selection in Part A.","definition_or_measurement_approach":"Normalised average nTrace value in lymph nodes corresponding to selected dose/time"}
• {"endpoint_text":"- Part A1: Dose-response curve (normalised average nTrace value for lymph nodes regardless of nTrace distribution)","definition_or_measurement_approach":"Dose-response curve using normalised average nTrace value regardless of nTrace distribution"}
• {"endpoint_text":"- Part A1: Time -response curve (normalised average nTrace value for lymph nodes regardless of nTrace distribution)","definition_or_measurement_approach":"Time-response curve using normalised average nTrace value regardless of nTrace distribution"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Dose-response curve using normalised average nTrace value for specified distribution corresponding to Part A1 selection"}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time-response curve using normalised average nTrace value corresponding to Part A1 selection"}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Dose-response curve using normalised average nTrace value regardless of distribution corresponding to Part A1 selection"}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time-response curve using normalised average nTrace value regardless of distribution corresponding to Part A1 selection"}
• {"endpoint_text":"- Part B: Normalised average nTrace value (in healthy lymph nodes regardless of nTrace distribution) corresponding to dose and time selection in Part A.","definition_or_measurement_approach":"Normalised average nTrace value in lymph nodes corresponding to dose/time selection from Part A"}

Secondary endpoints

• {"endpoint_text":"- 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?","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part A1: At what size of lymph nodes and in which sections and fractions are nTrace detectable in lymph nodes?","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part A1: At what size of lymph nodes and in which sections and fractions are nTrace showing an even distribution in lymph nodes?","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part A1: Frequency, seriousness, and intensity of adverse events (AEs).","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part A1: Frequency and nature of device deficiencies (DDs).","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part A1: Clinically significant changes in vital signs, ECG, safety laboratory measurements (haematology, clinical chemistry, coagulation) and physical examination findings.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part A1: Result of user experience questionnaire","definition_or_measurement_approach":""}
• {"endpoint_text":"- 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?","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part B: At what size of lymph nodes and in which sections and fractions are nTrace detectable in lymph nodes?","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part B: At what size of lymph nodes and in which sections and fractions are nTrace showing an even distribution in lymph nodes?","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part B: Number of suspected lymph nodes detected by NanoEcho diagnostic method, historic MRI and pathology.","definition_or_measurement_approach":"Comparison/counting across NanoEcho, historic MRI and pathology"}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Sensitivity and specificity using histopathology as the reference (true comparator)"}
• {"endpoint_text":"- Part B: Size of detectable lymph node with metastases","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part B: Size of detectable metastases.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part B: How far off from the tumour is tumour infiltration detectable?","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part B: Frequency, seriousness and intensity of AEs.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part B: Frequency and nature of DDs.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part B: Clinically significant changes in vital signs, ECG, safety laboratory measurements (haematology, clinical chemistry, coagulation) and physical examination findings.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part B: Result of user experience questionnaire.","definition_or_measurement_approach":""}
• {"endpoint_text":"- 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?","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part A2: At what size of lymph nodes and in which sections and fractions are nTrace detectable in lymph nodes?","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part A2: At what size of lymph nodes and in which sections and fractions are nTrace showing an even distribution in lymph nodes?","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part A2: Identify which probe cover that gives the best visualised images and highest nTrace value.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part A2: Frequency, seriousness, and intensity of adverse events (AEs) for the IMP and the medical device.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part A2: Frequency and nature of device deficiencies (DDs).","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part A2: Clinically significant changes in vital signs, ECG, safety laboratory measurements (haematology, clinical chemistry, coagulation) and physical examination findings.","definition_or_measurement_approach":""}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part B: Normalised average nTrace value (in unhealthy lymph nodes regardless of nTrace distribution) corresponding to dose and time selection in Part A.","definition_or_measurement_approach":""}

Sweden

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

27-11-2025

Processing Time Days

525

Number Of Sites

2

Number Of Participants

45

Primary sponsor

Full Name

NanoEcho AB (publ)

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden