Chronic Kidney Disease
Conditions
Keywords
Glomerular Filtration Rate, Transdermal fluorescence detection, Relmapirazin
Brief summary
The goal of this clinical trial was to compare transdermal glomerular filtration rate (tGFR) to plasma-derived indexed (to body surface area; BSA) GFR (nGFR) using MB-102 (relmapirazin) as the fluorescent compound. Adults with kidney function ranging from normal to Stage 4 chronic kidney disease (CKD) and participants 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 measured GFR using the MediBeacon Transdermal GFR Measurement System is comparable to the measured MB-102 plasma GFR * To evaluate the safety and tolerability of a single dose of MB-102 in study participants * To evaluate the safety and effectiveness of the MediBeacon Transdermal GFR Measurement System (TGFR) for the non-invasive transdermal fluorescence detection of MB-102 in participants Participants had a transdermal sensor placed on their upper chest, and the TGFR collected background fluorescence. Participants then received a single dose of MB-102. Blood samples were collected and fluorescent measurements were taken over a 12- to 24-hour period. 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 in those with and without normal kidney function and different skin coloration.
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 a transdermal sensor placed on their upper chest, and the MediBeacon Transdermal GFR Measurement System was initiated to collect background fluorescence. After collection of background fluorescence, participants received a single dose of MB-102.
Sponsors
MediBeacon
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
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 child-bearing 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 via PCR testing for COVID-19 (Vaccinated participants without symptoms of COVID-19 are not required to undergo PCR testing but may be tested at the discretion of the study site) * 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 * 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 scarring, 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 * 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 |
|---|---|---|
| Proportion of Transdermal Derived Glomerular Filtration Rate (tGFR) Values Within 30% of the nGFR Plasma-derived Indexed Glomerular Filtration Rate (nGFR) Values | 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. 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 95% confidence interval (CI). The performance goal was 0.85, and success for the study was defined as a lower limit of the 95% 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
China, 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 |
|---|---|
| eGFR ≥ 70 mL/Min/1.73 m^2 Participants with eGFR ≥ 70 mL/min/1.73 m\^2 received one 130 mg dose of MB-102 and a transdermal sensor was placed on their chest. Blood samples and fluorescent measurements were collected over 12 hours. | 130 |
| eGFR < 70 mL/Min/1.73 m^2 Participants with eGFR \< 70 mL/min/1.73 m\^2 received one 130 mg dose of MB-102 and a transdermal sensor was placed on their chest. Blood samples and fluorescent measurements were collected over 24 hours. | 119 |
| Total | 249 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 0 |
| Overall Study | Withdrew consent | 1 | 1 |
Baseline characteristics
| Characteristic | eGFR ≥ 70 mL/Min/1.73 m^2 | eGFR < 70 mL/Min/1.73 m^2 | Total |
|---|---|---|---|
| Age, Continuous | 46.9 years STANDARD_DEVIATION 14.19 | 61.5 years STANDARD_DEVIATION 13.45 | 53.9 years STANDARD_DEVIATION 15.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants | 14 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 94 Participants | 103 Participants | 197 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 37 Participants | 27 Participants | 64 Participants |
| Race (NIH/OMB) Black or African American | 33 Participants | 43 Participants | 76 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 58 Participants | 49 Participants | 107 Participants |
| Sex: Female, Male Female | 62 Participants | 45 Participants | 107 Participants |
| Sex: Female, Male Male | 68 Participants | 74 Participants | 142 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 130 | 0 / 119 |
| other Total, other adverse events | 3 / 130 | 7 / 119 |
| serious Total, serious adverse events | 0 / 130 | 0 / 119 |
Outcome results
Primary
Proportion of Transdermal Derived Glomerular Filtration Rate (tGFR) Values Within 30% of the nGFR Plasma-derived Indexed Glomerular Filtration Rate (nGFR) Values
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. 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 95% confidence interval (CI). The performance goal was 0.85, and success for the study was defined as a lower limit of the 95% CI greater than 0.85.
Time frame: Up to 24 hours following the study dose
Population: Modified intent-to-treat population (all participants enrolled in the study for whom an average session tGFR had been calculated, with no major protocol deviations and no outlier pharmacokinetic parameters)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| eGFR ≥ 70 mL/Min/1.73 m^2 | Proportion of Transdermal Derived Glomerular Filtration Rate (tGFR) Values Within 30% of the nGFR Plasma-derived Indexed Glomerular Filtration Rate (nGFR) Values | 0.96 Proportion of tGFR within 30% of nGFR |
| eGFR < 70 mL/Min/1.73 m^2 | Proportion of Transdermal Derived Glomerular Filtration Rate (tGFR) Values Within 30% of the nGFR Plasma-derived Indexed Glomerular Filtration Rate (nGFR) Values | 0.92 Proportion of tGFR within 30% of nGFR |
| All Participants | Proportion of Transdermal Derived Glomerular Filtration Rate (tGFR) Values Within 30% of the nGFR Plasma-derived Indexed Glomerular Filtration Rate (nGFR) Values | 0.94 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) |
|---|---|---|
| eGFR ≥ 70 mL/Min/1.73 m^2 | Number of Participants With Treatment-emergent Adverse Events Associated With MB-102 Administration | 1 Participants |
| eGFR < 70 mL/Min/1.73 m^2 | Number of Participants With Treatment-emergent Adverse Events Associated With MB-102 Administration | 0 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) |
|---|---|---|
| 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 |
| 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 |