Chronic Kidney Disease, Healthy Volunteers
Conditions
Brief summary
This is a Phase 1b, single-center, dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effect of RBT-1 in healthy volunteers and in subjects with Stage 3/4 CKD.
Interventions
DRUGRBT-1
Single intravenous administration
Sponsors
Renibus Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male and female subjects age 18 to 80 years (inclusive, at time of ICF). 2. Body weight \<125 kg. 3. Able and willing to comply with all study procedures. 4. Female subjects must be either post-menopausal for at least 1 year or surgically sterile (tubal ligation, hysterectomy or bilateral oophorectomy) for at least 3 months, or if of childbearing potential, have a negative pregnancy test and agree to use dual methods of contraception, or abstain from sexual activity from Screening until 28 days after study drug administration. Male subjects with female partners of childbearing potential must agree to use a highly effective method of contraception from screening until 28 days after study drug administration. All fertile men with female partners of childbearing potential should be instructed to contact the Investigator immediately if they suspect their partner might be pregnant (e.g., missed or late menstrual period) at any time during study participation. 5. CKD Stage 3 as determined by estimated glomerular filtration rate (eGFR) between 30-59 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. 6. CKD Stage 4 as determined by eGFR between 15-29 mL/min/1.73 m2 using the CKD-EPI equation.
Exclusion criteria
1. History of malignancy except carcinoma in situ in the cervix, early stage prostate cancer or non-melanoma skin cancers. 2. Use of investigational drugs or participation in another clinical trial within 30 days or 5 half-lives prior to screening, whichever is longer. 3. Serum ferritin \> 500 ng/ml or who have received IV iron within 28 days of screening, or currently being treated with oral iron. 4. Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study. 5. Any significant acute or chronic diseases. 6. Subjects with abnormal baseline liver tests or hepatitis serologies that suggest active infection. 7. Regular use of drugs of abuse and/or positive findings on urinary drug screening. 8. Current tobacco use and/or positive findings on urinary cotinine screening. 9. Subjects who are severely physically or mentally incapacitated and who, in the opinion of investigator, are unable to perform the subjects' tasks associated with the protocol. 10. Presence of any condition which, in the opinion of the investigator, places the subject at undue risk or potentially jeopardizes the quality of the data to be generated. 11. Subjects with history of photosensitivity or active skin disease 12. Known hypersensitivity or previous anaphylaxis to RBT-1 or to components thereof.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Effect of RBT-1 on Plasma Ferritin Levels | 24 hours post-infusion |
| Effect of RBT-1 on Plasma HO-1 Levels | 24 hours post-infusion |
| Effect of RBT-1 on Plasma IL-10 Levels | 24 hours post-infusion |
Countries
United States
Participant flow
Pre-assignment details
It was pre-specified to analyze healthy volunteers and participants with CKD Stage 3/Stage 4 together and report results by dose.
Participants by arm
| Arm | Count |
|---|---|
| 9 mg SnPP/240 mg FeS Single IV infusion | 6 |
| 27 mg SnPP/240 mg FeS Single IV infusion | 18 |
| 45 mg SnPP/240 mg FeS Single IV infusion | 6 |
| 63 mg SnPP/240 mg FeS Single IV infusion | 6 |
| 90 mg SnPP/240 mg FeS Single IV infusion | 18 |
| Total | 54 |
Baseline characteristics
| Characteristic | 9 mg SnPP/240 mg FeS | 27 mg SnPP/240 mg FeS | 45 mg SnPP/240 mg FeS | 63 mg SnPP/240 mg FeS | 90 mg SnPP/240 mg FeS | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 48.2 years STANDARD_DEVIATION 15.75 | 60.0 years STANDARD_DEVIATION 17.6 | 72.8 years STANDARD_DEVIATION 4.54 | 71.8 years STANDARD_DEVIATION 6.34 | 58.7 years STANDARD_DEVIATION 20.08 | 61.0 years STANDARD_DEVIATION 17.54 |
| BMI | 28.5 kg/m^2 STANDARD_DEVIATION 4.61 | 32.3 kg/m^2 STANDARD_DEVIATION 6.61 | 33.4 kg/m^2 STANDARD_DEVIATION 4.77 | 30.7 kg/m^2 STANDARD_DEVIATION 7.24 | 29.2 kg/m^2 STANDARD_DEVIATION 5.63 | 30.8 kg/m^2 STANDARD_DEVIATION 6.02 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 15 Participants | 6 Participants | 6 Participants | 17 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 180.9 cm STANDARD_DEVIATION 7.27 | 167.6 cm STANDARD_DEVIATION 9.26 | 166.4 cm STANDARD_DEVIATION 6.93 | 170.3 cm STANDARD_DEVIATION 7.41 | 168.5 cm STANDARD_DEVIATION 6.93 | 169.5 cm STANDARD_DEVIATION 8.66 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 0 Participants | 1 Participants | 6 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 3 Participants | 11 Participants | 6 Participants | 5 Participants | 11 Participants | 36 Participants |
| Sex: Female, Male Female | 0 Participants | 9 Participants | 1 Participants | 5 Participants | 7 Participants | 22 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 5 Participants | 1 Participants | 11 Participants | 32 Participants |
| Weight | 93.3 kg STANDARD_DEVIATION 16.37 | 90.3 kg STANDARD_DEVIATION 16.8 | 92.9 kg STANDARD_DEVIATION 17.2 | 88.4 kg STANDARD_DEVIATION 17.18 | 82.9 kg STANDARD_DEVIATION 15.69 | 88.2 kg STANDARD_DEVIATION 16.34 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 18 | 0 / 6 | 0 / 6 | 0 / 18 |
| other Total, other adverse events | 0 / 6 | 6 / 18 | 1 / 6 | 5 / 6 | 12 / 18 |
| serious Total, serious adverse events | 0 / 6 | 0 / 18 | 0 / 6 | 0 / 6 | 0 / 18 |
Outcome results
Primary
Effect of RBT-1 on Plasma Ferritin Levels
Time frame: 24 hours post-infusion
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 9 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma Ferritin Levels | 592.3 Percent change from baseline |
| 27 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma Ferritin Levels | 538.8 Percent change from baseline |
| 45 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma Ferritin Levels | 313.7 Percent change from baseline |
| 63 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma Ferritin Levels | 308.2 Percent change from baseline |
| 90 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma Ferritin Levels | 610.9 Percent change from baseline |
Primary
Effect of RBT-1 on Plasma HO-1 Levels
Time frame: 24 hours post-infusion
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 9 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma HO-1 Levels | -10.5 Percent change from baseline |
| 27 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma HO-1 Levels | 21 Percent change from baseline |
| 45 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma HO-1 Levels | 35.4 Percent change from baseline |
| 63 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma HO-1 Levels | 27.7 Percent change from baseline |
| 90 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma HO-1 Levels | 44.8 Percent change from baseline |
Primary
Effect of RBT-1 on Plasma IL-10 Levels
Time frame: 24 hours post-infusion
Population: Values at either baseline and/or the 24 h timepoint were missing from each of the treatment groups
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 9 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma IL-10 Levels | 66.8 Percent change from baseline |
| 27 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma IL-10 Levels | 95.5 Percent change from baseline |
| 45 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma IL-10 Levels | 574.6 Percent change from baseline |
| 63 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma IL-10 Levels | 333.5 Percent change from baseline |
| 90 mg SnPP/240 mg FeS | Effect of RBT-1 on Plasma IL-10 Levels | 201.4 Percent change from baseline |