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-9 in healthy volunteers and in subjects with Stage 3/4 CKD.
Interventions
DRUGRBT-9
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 a GFR between 30-59 ml/min as estimated using the CKD-EPI equation. 6. CKD stage 4 as determined by a GFR between 15-29 ml/min as estimated 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. Cancer free for less than 5 years. 2. Use of investigational drugs or participation in another clinical trial within 30 days or 5 half-lives prior to Screening, whichever was longer. 3. Serum ferritin \>500 ng/mL or received IV iron within 28 days of Screening. 4. Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study. 5. Any significant acute or chronic diseases, excluding CKD (≥ 15 ml/min); if CKD is present, those not at their baseline of renal function. 6. 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. 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. History of photosensitivity or active skin disease which, in the opinion of the Investigator, could increase the risk of photosensitivity. 12. Known hypersensitivity or previous anaphylaxis to RBT-9 or tin-based product.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of RBT-9 on Plasma Ferritin Levels | 24 hours post-infusion | Percent Change in Plasma Ferritin From Baseline to 24 hours |
| Effect of RBT-9 on Plasma HO-1 Levels | 24 hours post-infusion | Percent Change in Plasma HO-1 From Baseline to 24 hours |
| Effect of RBT-9 on Plasma IL-10 Levels | 24 hours post-infusion | Percent Change in Plasma IL-10 From Baseline to 24 hours |
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 Single IV infusion | 6 |
| 27 mg Single IV infusion | 18 |
| 90 mg Single IV infusion | 18 |
| Total | 42 |
Baseline characteristics
| Characteristic | 9 mg | 27 mg | 90 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 45.5 years STANDARD_DEVIATION 11.69 | 59.3 years STANDARD_DEVIATION 18.5 | 64.3 years STANDARD_DEVIATION 15.29 | 59.5 years STANDARD_DEVIATION 17.16 |
| BMI | 29.8 kg/m2 STANDARD_DEVIATION 3.87 | 30.8 kg/m2 STANDARD_DEVIATION 6.22 | 30.5 kg/m2 STANDARD_DEVIATION 6.71 | 30.5 kg/m2 STANDARD_DEVIATION 6.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 15 Participants | 15 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 175.9 cm STANDARD_DEVIATION 12 | 168.4 cm STANDARD_DEVIATION 10.11 | 170.3 cm STANDARD_DEVIATION 8.96 | 170.3 cm STANDARD_DEVIATION 9.97 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 5 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) White | 2 Participants | 11 Participants | 10 Participants | 23 Participants |
| Sex: Female, Male Female | 0 Participants | 9 Participants | 8 Participants | 17 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 10 Participants | 25 Participants |
| Weight | 92.6 kg STANDARD_DEVIATION 18.79 | 87.2 kg STANDARD_DEVIATION 16.84 | 88.6 kg STANDARD_DEVIATION 20.04 | 88.6 kg STANDARD_DEVIATION 18.18 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 2 / 6 | 4 / 18 | 14 / 18 |
| serious Total, serious adverse events | 0 / 6 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Effect of RBT-9 on Plasma Ferritin Levels
Percent Change in Plasma Ferritin From Baseline to 24 hours
Time frame: 24 hours post-infusion
Population: 1 value was missing at the 24 h timepoint from the 90 mg group
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 9 mg | Effect of RBT-9 on Plasma Ferritin Levels | -9.83 Percent change from baseline |
| 27 mg | Effect of RBT-9 on Plasma Ferritin Levels | 7.66 Percent change from baseline |
| 90 mg | Effect of RBT-9 on Plasma Ferritin Levels | 39.37 Percent change from baseline |
Primary
Effect of RBT-9 on Plasma HO-1 Levels
Percent Change in Plasma HO-1 From Baseline to 24 hours
Time frame: 24 hours post-infusion
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 9 mg | Effect of RBT-9 on Plasma HO-1 Levels | -16.07 Percent change from baseline |
| 27 mg | Effect of RBT-9 on Plasma HO-1 Levels | 10.46 Percent change from baseline |
| 90 mg | Effect of RBT-9 on Plasma HO-1 Levels | 33.37 Percent change from baseline |
Primary
Effect of RBT-9 on Plasma IL-10 Levels
Percent Change in Plasma IL-10 From Baseline to 24 hours
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 | Effect of RBT-9 on Plasma IL-10 Levels | 1.07 Percent change from baseline |
| 27 mg | Effect of RBT-9 on Plasma IL-10 Levels | 153.11 Percent change from baseline |
| 90 mg | Effect of RBT-9 on Plasma IL-10 Levels | 752.53 Percent change from baseline |