Randomized phase 2 study of GMI-1070 in SCD: Reduction in time to resolution of vaso-occlusive events and decreased opioid use

Marilyn J. Telen, Theodore Wun, Timothy L. McCavit, Laura M. De Castro, Lakshmanan Krishnamurti, Sophie Lanzkron, Lewis L. Hsu, Wally R. Smith, Seungshin Rhee, John L. Magnani, Helen Thackray

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Treatment of vaso-occlusive crises (VOC) or events in sickle cell disease (SCD) remains limited to symptom relief with opioids. Animal models support the effectiveness of the pan-selectin inhibitor GMI-1070 in reducing selectin-mediated cell adhesion and abrogating VOC. We studied GMI-1070 in a prospective multicenter, randomized, placebo-controlled, double-blind, phase 2 study of 76 SCD patients with VOC. Study drug (GMI-1070 or placebo) was given every 12 hours for up to 15 doses. Other treatment was per institutional standard of care. All subjects reached the composite primary end point of resolution of VOC. Although time to reach the composite primary end point was not statistically different between the groups, clinically meaningful reductions in mean and median times to VOC resolution of 41 and 63 hours (28% and 48%, P = .19 for both) were observed in the active treatment group vs the placebo group. As a secondary end point, GMI-1070 appeared safe in acute vaso-occlusion, and adverse events were not different in the two arms. Also in secondary analyses, mean cumulative IV opioid analgesic use was reduced by 83% with GMI-1070 vs placebo (P = .010). These results support a phase 3 study of GMI-1070 (now rivipansel) for SCD VOC. This trial was registered at www.clinicaltrials.gov as #NCT01119833.

Original languageEnglish (US)
Pages (from-to)2656-2664
Number of pages9
JournalBlood
Volume125
Issue number17
DOIs
StatePublished - Apr 23 2015

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Sickle Cell Anemia
Opioid Analgesics
Placebos
Selectins
Cell adhesion
Composite materials
Standard of Care
Cell Adhesion
GMI-1070
Animals
Therapeutics
Animal Models
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Telen, M. J., Wun, T., McCavit, T. L., De Castro, L. M., Krishnamurti, L., Lanzkron, S., ... Thackray, H. (2015). Randomized phase 2 study of GMI-1070 in SCD: Reduction in time to resolution of vaso-occlusive events and decreased opioid use. Blood, 125(17), 2656-2664. https://doi.org/10.1182/blood-2014-06-583351

Randomized phase 2 study of GMI-1070 in SCD : Reduction in time to resolution of vaso-occlusive events and decreased opioid use. / Telen, Marilyn J.; Wun, Theodore; McCavit, Timothy L.; De Castro, Laura M.; Krishnamurti, Lakshmanan; Lanzkron, Sophie; Hsu, Lewis L.; Smith, Wally R.; Rhee, Seungshin; Magnani, John L.; Thackray, Helen.

In: Blood, Vol. 125, No. 17, 23.04.2015, p. 2656-2664.

Research output: Contribution to journalArticle

Telen, MJ, Wun, T, McCavit, TL, De Castro, LM, Krishnamurti, L, Lanzkron, S, Hsu, LL, Smith, WR, Rhee, S, Magnani, JL & Thackray, H 2015, 'Randomized phase 2 study of GMI-1070 in SCD: Reduction in time to resolution of vaso-occlusive events and decreased opioid use', Blood, vol. 125, no. 17, pp. 2656-2664. https://doi.org/10.1182/blood-2014-06-583351
Telen, Marilyn J. ; Wun, Theodore ; McCavit, Timothy L. ; De Castro, Laura M. ; Krishnamurti, Lakshmanan ; Lanzkron, Sophie ; Hsu, Lewis L. ; Smith, Wally R. ; Rhee, Seungshin ; Magnani, John L. ; Thackray, Helen. / Randomized phase 2 study of GMI-1070 in SCD : Reduction in time to resolution of vaso-occlusive events and decreased opioid use. In: Blood. 2015 ; Vol. 125, No. 17. pp. 2656-2664.
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