Head and Neck Neoplasms, Imaging, Nerve Injury, Parotid Neoplasm, Surgery, Thyroid Neoplasms
Conditions
Keywords
Nerve, Fluorescence, Surgery, Imaging, Real-time, Intraoperative, Highlighting
Brief summary
Bevonescein to Highlight Nerves in Patients Undergoing Head & Neck Surgery
Detailed description
This study will evaluate the safety, tolerability, and efficacy of Bevonescein (ALM-488) administered as an intravenous (IV) infusion to patients undergoing head & neck surgery. The study will also characterize the pharmacokinetics of Bevonescein (ALM-488) in this subject population and determine the dose of Bevonescein (ALM-488) needed to generate a fluorescence signal in nerve tissue to enable fluorescence recordings and image analysis with an imaging system. The study will also evaluate the effect of timing of Bevonescein (ALM-488) administration, relative to surgery, on fluorescence characteristics.
Interventions
DRUGBevonescein
Bevonescein Sterile Solution is an intravenously administered, synthetic, peptide dye conjugate indicated for the real-time intraoperative fluorescence detection and localization of nerve tissue.
Sponsors
Alume Biosciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
This is a Phase 1/Phase 2 study in patients undergoing Head & Neck Surgery.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. A neoplasm located in the head and neck. 2. Primary surgical treatment is by parotidectomy, or thyroidectomy, or cervical neck dissection. 3. Can understand and is willing to sign a written informed consent document. 4. ≥18 years of age. 5. Life expectancy of at least 6 months. 6. Normal liver and kidney functions. 7. If of childbearing potential, must have a negative urine or serum pregnancy test and be using a medically acceptable form of contraception (e.g., hormonal birth control, intrauterine devices, double-barrier method) or abstinence. The subject, if male, must use a medically acceptable form of contraception (e.g. condom) or abstinence. 8. Plans to undergo head and neck surgery.
Exclusion criteria
1. Prior radiation or chemotherapy for any prior head and neck neoplasm. 2. Open surgery in the ipsilateral head and neck within 1 year. 3. Abnormal cardiac rhythm not controlled with medication, history of stroke, coronary events and/or heart failure within 1 year. 4. Current evidence of renal disease. 5. Pregnant or breastfeeding. 6. Unresolved acute toxicity from prior anti-cancer therapy. 7. History of fluorescein allergy. 8. Any other criteria deemed by the Principal Investigator that may prevent the patient from successfully completing the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety - The Number of Patients With ALM-488 Related Adverse Events | 28 (+5) days | The number of patients with ALM-488 related Adverse Events according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time of Peak ALM-488 Concentration in Plasma (Cmax) | 28 (+5) days | Time of peak ALM-488 concentration in plasma following intravenous ALM-488 infusion (hours). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Defining 100mg This arm of the study will include Dose Defining cohort at 100mg. ALM-488: ALM-488 Sterile Solution is an intravenously administered, synthetic, peptide dye conjugate indicated for the real-time intraoperative fluorescence detection and localization of nerve tissue. | 3 |
| Dose Defining 200mg This arm of the study will include Dose Defining cohort at 200mg. ALM-488: ALM-488 Sterile Solution is an intravenously administered, synthetic, peptide dye conjugate indicated for the real-time intraoperative fluorescence detection and localization of nerve tissue. | 3 |
| Dose Defining 400mg This arm of the study will include Dose Defining cohort at 400mg. ALM-488: ALM-488 Sterile Solution is an intravenously administered, synthetic, peptide dye conjugate indicated for the real-time intraoperative fluorescence detection and localization of nerve tissue. | 3 |
| Dose Defining 500mg This arm of the study will include Dose Defining cohort at 500mg. ALM-488: ALM-488 Sterile Solution is an intravenously administered, synthetic, peptide dye conjugate indicated for the real-time intraoperative fluorescence detection and localization of nerve tissue. | 3 |
| Dose Defining 600mg This arm of the study will include Dose Defining cohort at 600mg. ALM-488: ALM-488 Sterile Solution is an intravenously administered, synthetic, peptide dye conjugate indicated for the real-time intraoperative fluorescence detection and localization of nerve tissue. | 3 |
| Dose Timing 1-3hrs This arm of the study will include Dose Timing cohorts of ALM-488 administration 1-3 hrs before surgery.
ALM-488: ALM-488 Sterile Solution is an intravenously administered, synthetic, peptide dye conjugate indicated for the real-time intraoperative fluorescence detection and localization of nerve tissue. | 6 |
| Dose Timing 3-5 Hrs This arm of the study will include Dose Timing cohorts of ALM-488 administration 3-5 hrs before surgery.
ALM-488: ALM-488 Sterile Solution is an intravenously administered, synthetic, peptide dye conjugate indicated for the real-time intraoperative fluorescence detection and localization of nerve tissue. | 6 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | COVID-19 related hospitalization | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Dose Defining 200mg | Dose Defining 400mg | Dose Defining 500mg | Dose Defining 600mg | Dose Timing 1-3hrs | Dose Timing 3-5 Hrs | Dose Defining 100mg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 4 Participants | 0 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 5 Participants | 2 Participants | 3 Participants | 20 Participants |
| Age, Continuous | 49.7 years | 56.7 years | 68 years | 56.7 years | 36 years | 65 years | 41 years | 52.6 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 4 Participants | 5 Participants | 2 Participants | 15 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 3 participants | 3 participants | 6 participants | 6 participants | 3 participants | 27 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 5 Participants | 2 Participants | 2 Participants | 13 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 1 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 2 / 3 | 1 / 3 | 1 / 3 | 0 / 3 | 2 / 3 | 3 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 1 / 3 | 0 / 6 | 1 / 6 |
Outcome results
Primary
Safety - The Number of Patients With ALM-488 Related Adverse Events
The number of patients with ALM-488 related Adverse Events according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time frame: 28 (+5) days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Defining 100mg | Safety - The Number of Patients With ALM-488 Related Adverse Events | 0 Participants |
| Dose Defining 200mg | Safety - The Number of Patients With ALM-488 Related Adverse Events | 0 Participants |
| Dose Defining 400mg | Safety - The Number of Patients With ALM-488 Related Adverse Events | 0 Participants |
| Dose Defining 500mg | Safety - The Number of Patients With ALM-488 Related Adverse Events | 0 Participants |
| Dose Defining 600mg | Safety - The Number of Patients With ALM-488 Related Adverse Events | 0 Participants |
| Dose Timing 1-3hrs | Safety - The Number of Patients With ALM-488 Related Adverse Events | 0 Participants |
| Dose Timing 3-5 Hrs. | Safety - The Number of Patients With ALM-488 Related Adverse Events | 0 Participants |
Other Pre-specified
Time of Peak ALM-488 Concentration in Plasma (Cmax)
Time of peak ALM-488 concentration in plasma following intravenous ALM-488 infusion (hours).
Time frame: 28 (+5) days
Population: Patients were accrued into the Dose Defining Cohorts (Dose Escalation/De-Escalation) and the Dose Timing Cohorts using inclusion and exclusion criteria as specified in the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Defining 100mg | Time of Peak ALM-488 Concentration in Plasma (Cmax) | 0.50 hours | Standard Deviation 0 |
| Dose Defining 200mg | Time of Peak ALM-488 Concentration in Plasma (Cmax) | 0.50 hours | Standard Deviation 0 |
| Dose Defining 400mg | Time of Peak ALM-488 Concentration in Plasma (Cmax) | 0.50 hours | Standard Deviation 0 |
| Dose Defining 500mg | Time of Peak ALM-488 Concentration in Plasma (Cmax) | 0.42 hours | Standard Deviation 0.14 |
| Dose Defining 600mg | Time of Peak ALM-488 Concentration in Plasma (Cmax) | 0.42 hours | Standard Deviation 0.14 |
| Dose Timing 1-3hrs | Time of Peak ALM-488 Concentration in Plasma (Cmax) | 0.42 hours | Standard Deviation 0.13 |
| Dose Timing 3-5 Hrs. | Time of Peak ALM-488 Concentration in Plasma (Cmax) | 0.40 hours | Standard Deviation 0.14 |