Kidney Diseases, Kidney Failure, Kidney Injury
Conditions
Keywords
Glomerular Filtration Rate, Relmapirazin, Iohexol, Pharmacokinetics, Transdermal fluorescence detection, MB-102
Brief summary
The goal of this clinical trial was to compare transdermal glomerular filtration rate (tGFR) to plasma-derived indexed GFR (nGFR) using MB-102 (relmapirazin) as the fluorescent compound. Adults with kidney function ranging from estimated glomerular filtration rate (eGFR) \<120 to \>15 mL/min/1.73 m2 and spanning the entire range of human skin colors as defined by the Fitzpatrick Skin Scale (FSS) were included in the study. The main questions that the study aimed to answer were: * To establish that the MB-102 transdermal fluorescence assessed GFR using the MediBeacon Transdermal GFR System with the TGFR reusable sensor with disposable adhesive ring was comparable to the measured MB-102 plasma GFR. * To evaluate the safety and effectiveness of the MediBeacon Transdermal GFR System and the TGFR reusable sensor with disposable adhesive ring for the non-invasive transdermal fluorescence detection of MB-102 in participants On dosing day, participants had the TGFR reusable sensor with disposable adhesive ring placed on their chest, and the MediBeacon Transdermal GFR System initiated to collect background fluorescence. When this was completed, participants then received a single dose of MB-102. Blood samples were collected and fluorescent measurements were taken over a 12- or 24-hour (or longer) period, depending upon enrollment group. For those with significant renal compromise, fluorescent measurements were continued until the sensor no longer detected MB-102 in the body. Following completion of the treatment period, participants returned to the study center approximately 1 week later for a safety follow-up visit. Researchers compared the results to see if the transdermal GFR measurements were comparable to the measured plasma GFR.
Interventions
DRUGMB-102
18.6 mg/mL in a 7.0 mL volume administered by intravenous injection over 30 - 60 seconds, followed by a 10 mL normal saline flush administered intravenously over 30 - 60 seconds
On treatment day, participants had the TGFR reusable sensor with disposable adhesive ring placed on their chest, and the MediBeacon® Transdermal GFR Measurement System was initiated to collect background fluorescence. When this was completed, participants received a single dose of MB-102. Fluorescent measurements were collected for 12-24 hours. For those with significant renal compromise, fluorescent measurements were continued until the sensor no longer detected MB-102 in the body.
Sponsors
MediBeacon
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Eligible female non-pregnant participants who are either not of child-bearing potential or willing to use adequate contraception during the trial * Males must be willing to practice abstinence or utilize adequate contraception from dosing day to at least 7 days post-dose * For women of childbearing potential, the participant should have a negative serum pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly i.e. abstinence, oral contraceptive either combined or progesterone alone; injectable progesterone, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, IUD device or system or male partner sterilization * Men will not donate sperm during the study and for 1 month following the last dose of study drug. * Participants who are capable of directly providing informed consent and who can comply with the requirements and restrictions required by the protocol * Adequate venous access sufficient to allow blood sampling per protocol requirements
Exclusion criteria
* Participants positive for COVID-19 at the time of dosing * Recent donation or loss of blood or plasma: 100 mL to 499 mL within 30 days prior to the initial dose of the study medication; or more than 499 mL within 56 days prior to the initial dose of study medication * Non-steroidal anti-inflammatory (NSAID) use within 3 days of MB-102 dosing * The participant has participated in a clinical trial and has received an investigational product within the following time ranges: prior to the first dosing day in the current study: either 30 days or 5 half-lives of the investigational product (whichever duration is longer). * History of skin sensitivity to adhesives (e.g. Band-Aids, surgical tape) * History of severe allergic hypersensitivity reactions (unacceptable adverse events) or anaphylactoid reaction to any allergen including drugs, MB-102 or other related products (intolerance to a drug is not considered a drug allergy). * Any characteristics which, in the opinion of the investigator, makes the participant a poor candidate for participation in the clinical trial * Significant scaring, tattoos or alterations in pigmentation on the sternum or other sensor location testing areas that would alter sensor readings versus other areas of the skin * Use of tanning sprays, tanning products etc. on the upper chest within 2 weeks of dosing day * Use make-up, lotions, Vaseline or other products on the area of the upper chest on the day prior to or the day of dosing * Any serious or uncontrolled medical disorder, active infection, physical exam finding, laboratory finding, or psychiatric condition that in the opinion of the investigator would limit the participant's ability to complete study requirements or may put the participant at increased risk or compromise the interpretability of study results. * Currently receiving dialysis * Currently anuric * Positive serum pregnancy test * Participants with an eGFR \> 120 mL/min/1.73m\^2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of Transdermal Derived Glomerular Filtration Rate (tGFR) to the Plasma-derived Indexed Glomerular Filtration Rate (nGFR) | Up to 24 hours following the study dose | The performance measure of P30 is defined as the proportion of transdermal derived GFR values that are within 30% of the measured plasma-derived GFR across all participants. The comparison of transdermal derived glomerular filtration rate (tGFR) with respect to the plasma-derived indexed glomerular filtration rate (nGFR) was calculated with a double-sided 97% confidence interval (CI). The performance goal was 0.85, and success for the study was defined as a lower limit of the 97% CI greater than 0.85. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events Associated With MB-102 Administration | From the time of dosing through the follow-up visit, up to 10 days | An adverse event is defined as any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, temporally associated with the use of a medicinal product, whether or not related to the investigational medical device or drug. |
| Number of Participants With Treatment-emergent Adverse Events Associated With the MediBeacon Transdermal GFR Measurement System Device | From the time of dosing through the follow-up visit, up to 10 days | An adverse event is defined as any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, temporally associated with the use of a medicinal product, whether or not related to the investigational medical device or drug. |
Countries
United States
Participant flow
Pre-assignment details
Safety Population: all participants who enrolled in the study and were dosed with MB-102
Participants by arm
| Arm | Count |
|---|---|
| Participants With eGFR ≥ 70 mL/Min/1.73 m^2 A TGFR Reusable Sensor with Disposable Adhesive Ring was placed on participants' chests at least 15 minutes prior to dosing on treatment day, and the MediBeacon Transdermal GFR System was initiated to collect background fluorescence. After the collection of background fluorescence, a single dose of MB-102 (130 mg) was administered intravenously to participants with estimated glomerular filtration rate (eGFR) eGFR ≥ 70 mL/min/1.73 m\^2. Approximately half of the participants had Fitzpatrick Scale Type I, II or III, and half had Type IV, V and VI skin color type. Blood samples and fluorescent measurements were collected over 12 hours. | 84 |
| Participants With eGFR < 70 mL/Min/1.73 m^2 A TGFR Reusable Sensor with Disposable Adhesive Ring was placed on participants' chests at least 15 minutes prior to dosing on treatment day, and the MediBeacon Transdermal GFR System was initiated to collect background fluorescence. After the collection of background fluorescence, a single dose of MB-102 (130 mg) was administered intravenously to participants with estimated glomerular filtration rate eGFR \< 70 mL/min/1.73 m\^2. Approximately half of the participants had Fitzpatrick Scale Type I, II or III, and half had Type IV, V and VI skin color type. Blood samples and fluorescent measurements were collected over 24 hours. | 65 |
| Total | 149 |
Baseline characteristics
| Characteristic | Participants With eGFR < 70 mL/Min/1.73 m^2 | Total | Participants With eGFR ≥ 70 mL/Min/1.73 m^2 |
|---|---|---|---|
| Age, Continuous | 66.0 years STANDARD_DEVIATION 8.62 | 57.8 years STANDARD_DEVIATION 13.3 | 51.5 years STANDARD_DEVIATION 12.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 26 Participants | 60 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 89 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 31 Participants | 57 Participants | 26 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown or not reported | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 30 Participants | 82 Participants | 52 Participants |
| Sex: Female, Male Female | 33 Participants | 70 Participants | 37 Participants |
| Sex: Female, Male Male | 32 Participants | 79 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 65 |
| other Total, other adverse events | 2 / 84 | 5 / 65 |
| serious Total, serious adverse events | 0 / 84 | 0 / 65 |
Outcome results
Primary
Correlation of Transdermal Derived Glomerular Filtration Rate (tGFR) to the Plasma-derived Indexed Glomerular Filtration Rate (nGFR)
The performance measure of P30 is defined as the proportion of transdermal derived GFR values that are within 30% of the measured plasma-derived GFR across all participants. The comparison of transdermal derived glomerular filtration rate (tGFR) with respect to the plasma-derived indexed glomerular filtration rate (nGFR) was calculated with a double-sided 97% confidence interval (CI). The performance goal was 0.85, and success for the study was defined as a lower limit of the 97% CI greater than 0.85.
Time frame: Up to 24 hours following the study dose
Population: Modified intent-to-measure population (all participants enrolled in the study for whom an average session tGFR or an average snapshot tGFR had been calculated, with no major protocol deviations and no outlier pharmacokinetic parameters)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With eGFR ≥ 70 mL/Min/1.73 m^2 | Correlation of Transdermal Derived Glomerular Filtration Rate (tGFR) to the Plasma-derived Indexed Glomerular Filtration Rate (nGFR) | 0.950 Proportion of tGFR within 30% of nGFR |
| Participants With eGFR < 70 mL/Min/1.73 m^2 | Correlation of Transdermal Derived Glomerular Filtration Rate (tGFR) to the Plasma-derived Indexed Glomerular Filtration Rate (nGFR) | 0.971 Proportion of tGFR within 30% of nGFR |
Secondary
Number of Participants With Treatment-emergent Adverse Events Associated With MB-102 Administration
An adverse event is defined as any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, temporally associated with the use of a medicinal product, whether or not related to the investigational medical device or drug.
Time frame: From the time of dosing through the follow-up visit, up to 10 days
Population: Safety Population: all participants who enrolled in the study and were dosed with MB-102
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With eGFR ≥ 70 mL/Min/1.73 m^2 | Number of Participants With Treatment-emergent Adverse Events Associated With MB-102 Administration | 1 Participants |
| Participants With eGFR < 70 mL/Min/1.73 m^2 | Number of Participants With Treatment-emergent Adverse Events Associated With MB-102 Administration | 1 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events Associated With the MediBeacon Transdermal GFR Measurement System Device
An adverse event is defined as any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, temporally associated with the use of a medicinal product, whether or not related to the investigational medical device or drug.
Time frame: From the time of dosing through the follow-up visit, up to 10 days
Population: Safety Population: all participants who enrolled in the study and were dosed with MB-102
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With eGFR ≥ 70 mL/Min/1.73 m^2 | Number of Participants With Treatment-emergent Adverse Events Associated With the MediBeacon Transdermal GFR Measurement System Device | 0 Participants |
| Participants With eGFR < 70 mL/Min/1.73 m^2 | Number of Participants With Treatment-emergent Adverse Events Associated With the MediBeacon Transdermal GFR Measurement System Device | 0 Participants |