RBT-1 Safety and Cytoprotective Response Biomarkers in Healthy Volunteers and Subjects with CKD
Bibliographic record
Abstract
Background: RBT-1 (stannous protoporphyrin [SnPP] with iron sucrose [FeS]) is a novel drug designed to precondition organs to prevent acute injury via activation of Nrf2, anti-inflammatory, and iron sequestering pathways. Pretreatment with RBT-1 in several animal models of acute kidney injury (AKI) has demonstrated protection from AKI in conjunction with upregulation of cytoprotective proteins. Here, we report results of a Phase 1b study of RBT-1 that assessed safety and cytoprotective response biomarker induction in healthy volunteers and subjects with stage 3 and 4 chronic kidney disease (CKD). Methods: Fifty-four (54) subjects (18 healthy volunteers and 36 subjects with CKD) were enrolled and received a single IV dose of RBT-1 (9, 27, 45, 63, or 90 mg SnPP with 240 mg FeS). Plasma heme oxygenase-1 (HO-1), interleukin-10 (IL-10) and ferritin were selected as surrogate measures of organ protective activity. Safety was assessed through Day 29, and cytoprotective response biomarkers were assessed through 168 hours post-dose. Results: RBT-1 was well tolerated in both healthy volunteers and subjects with CKD. The most common treatment-emergent adverse event was photosensitivity reaction (a known reaction to SnPP), which occurred in 15 subjects (27.8%) and was more commonly observed in the higher dose groups (63 and 90 mg SnPP/240 mg FeS). Photosensitivity was transient and generally mild in intensity. No serious adverse events were reported. RBT-1 induced dose-dependent, statistically significant increases in cytoprotective response biomarkers in both healthy volunteers and subjects with CKD. Peak increases from baseline in healthy volunteers and subjects with CKD were: 386% and 402% for HO-1, respectively; 99% and 332% for IL-10, respectively; and 1552% and 469% for ferritin, respectively. Conclusions: RBT-1 is well tolerated with a similar safety profile in healthy volunteers and subjects with CKD Stage 3 or 4 and elicits a biomarker response in humans that is associated with RBT-1-mediated organ protection in animal models of AKI. The positive safety and biomarker efficacy data provide a strong scientific basis to study RBT-1 as an AKI prevention strategy in patients undergoing elective cardiac surgery. Funding: Commercial Support - Renibus Therapeutics, Inc.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".