Chronic Kidney Disease, Healthy Volunteers
Conditions
Brief summary
This is a Phase 1b, single center, dose-escalating study evaluating the safety, tolerability, and pharmacodynamic effect of RBT-3 in healthy volunteers and in subjects with stage 3-4 chronic kidney disease.
Interventions
DRUGRBT-3
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 8 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 8 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 as determined by estimated glomerular filtration rate (eGFR) between 15-59 ml/min as estimated using the CKD-EPI equation (CKD class 3-4).
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. 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 (eGFR ≥15 ml/min). 6. Regular use of drugs of abuse and/or positive findings on urinary drug screening. 7. Current tobacco use and/or positive findings on urinary cotinine screening. 8. 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. 9. 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. 10. Known hypersensitivity or previous anaphylaxis to FeS.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Effect of RBT-3 on Plasma Ferritin Levels | 24 hours post-infusion |
| Effect of RBT-3 on Plasma HO-1 Levels | 24 hours post-infusion |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 120 mg Single IV infusion | 6 |
| 240 mg Single IV infusion | 6 |
| 360 mg Single IV infusion | 6 |
| Total | 18 |
Baseline characteristics
| Characteristic | 120 mg | 240 mg | 360 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 60.0 years STANDARD_DEVIATION 7.32 | 57.7 years STANDARD_DEVIATION 14.87 | 63.3 years STANDARD_DEVIATION 11.83 | 60.3 years STANDARD_DEVIATION 11.3 |
| 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 | 1 Participants | 2 Participants | 2 Participants | 5 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 | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 4 Participants | 3 Participants | 12 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 2 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Effect of RBT-3 on Plasma Ferritin Levels
Time frame: 24 hours post-infusion
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 120 mg | Effect of RBT-3 on Plasma Ferritin Levels | 2.49 Ratio (24 h post-infusion over baseline) |
| 240 mg | Effect of RBT-3 on Plasma Ferritin Levels | 4.42 Ratio (24 h post-infusion over baseline) |
| 360 mg | Effect of RBT-3 on Plasma Ferritin Levels | 4.90 Ratio (24 h post-infusion over baseline) |
Primary
Effect of RBT-3 on Plasma HO-1 Levels
Time frame: 24 hours post-infusion
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 120 mg | Effect of RBT-3 on Plasma HO-1 Levels | 0.0171 Ratio (24 h post-infusion over baseline) |
| 240 mg | Effect of RBT-3 on Plasma HO-1 Levels | -0.7086 Ratio (24 h post-infusion over baseline) |
| 360 mg | Effect of RBT-3 on Plasma HO-1 Levels | -0.0641 Ratio (24 h post-infusion over baseline) |