A trial investigating rivipansel in treatment of vaso-occlusive crisis (VOC) requiring hospitalization in patients with sickle cell disease did not meet its primary or secondary efficacy endpoints, but it appeared safe and well tolerated. Results were published in the journal Blood.
The phase 3, double-blind, randomized, controlled RESET trial (ClinicalTrials.gov Identifier: NCT02187003) included 2 study arms. Patients were randomly assigned 1:1 to receive either rivipansel or placebo. Rivipansel was given either until meeting discharge criteria or until receipt of a total of 15 doses, with dosage based on weight and age. The trial also had an open-label extension (OLE; ClinicalTrials.gov Identifier: NCT02433158), in which all patients received rivipansel.
The study’s primary efficacy endpoint was the duration of time from initiation of study drug to the time at which patients met all readiness criteria for discharge (TTRFD). Several secondary efficacy endpoints and safety endpoints were also assessed.
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The RESET analysis population included 173 patients in the rivipansel arm and 172 in the placebo arm. Discontinuations occurred with 15.6% of patients in the rivipansel arm and 18.0% in the placebo arm. The OLE enrolled 153 patients, 46.9% of whom had originally been in the rivipansel arm of the RESET study, whereas 53.1% had been in the placebo arm.
In the RESET study, the median TTRFD of the rivipansel arm was 87.8 hours (95% CI, 65.7-100.2), compared with 93.5 hours (95% CI, 74.7-109.7) for the placebo arm. This reflected a difference of -5.7 hours (hazard ratio [HR], 0.97; P =.79) for the rivipansel arm with respect to the placebo arm. Protocol-defined subgroup analyses also did not show significant differences.
Reported secondary endpoints also did not reflect statistically significant differences between treatment arms. The difference in the median time to hospital discharge (TTD) was -3.9 hours (HR, 0.96, 95% CI, 0.77-1.19; P =.72) between rivipansel and placebo arms. The difference in median time to discontinuation of intravenous opioids (TTDIVO) was -1.25 hours (HR, 1.02, 95% CI, 0.82-1.26; P =.86). Additionally, the difference in median cumulative intravenous opioid use (CIVO) was -0.06 morphine-equivalent units (MEU)/kg (ratio of medians, 1.01, 95% CI, 0.65-1.57; P =.85).
The OLE study showed a median TTD of 80.89 hours (90% CI, 67.07-90.33) in early-treatment participants, with a median TTDIVO of 63.87 hours (90% CI, 35.02-76.05), and a median CIVO of 1.83 MEU/kg (interquartile range, 0.61-5.15).
In RESET study safety population, adverse events (AEs) were reported in 88.3% of patients in the rivipansel arm and in 82.3% of patients in the placebo arm. Treatment-related AEs were reportedly comparable between study arms, and serious AEs and acute chest syndrome reportedly occurred at similar rates between study arms.
“In this phase 3 study, rivipansel treatment was well tolerated but failed to show improvement compared with placebo for the primary and secondary efficacy end points,” the investigators wrote in their report. However, post hoc analyses of the RESET study suggested the timing of administration of rivipansel may be a factor in some metrics of efficacy.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Reference
Dampier CD, Telen MJ, Wun T, et al; on behalf of the RESET Investigators. A randomized clinical trial of the efficacy and safety of rivipansel for sickle cell vaso-occlusive crisis. Blood. 2023;141(2):168-179. doi:10.1182/blood.2022015797
