Safety of Rivipansel (GMI-1070) in the Treatment of One or More Vaso-Occlusive Crises in Hospitalized Subjects With Sickle Cell Disease

Study Overview
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Brief Summary
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This is an open label extension study in subjects with Sickle Cell Disease (SCD) who have completed the double blind Phase 3 study (B5201002).

Detailed Description
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This is an open label extension study in subjects who are 6 years of age or older with Sickle Cell Disease (SCD) who have completed the double blind Phase 3 study (B5201002). This study is designed to evaluate the safety and describe the efficacy of rivipansel as treatment for one or more vaso-occlusive crisis (VOC) events in hospitalized subjects with SCD.

Official Title
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An Open-Label Extension Study to Evaluate the Safety of Rivipansel (GMI-1070) in the Treatment of One or More Vaso-Occlusive Crises in Hospitalized Subjects With Sickle Cell Disease

Conditions
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Sickle Cell Anemia, Sickle Cell Disease, Sickle Cell Disorders, Pain Crisis, Vaso-occlusive Crisis

Intervention / Treatment
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* Drug: Rivipansel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completion of Study B5201002. Documented diagnosis of SCD. At least 6 years of age. Male and female subjects of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study. Diagnosis of VOC necessitating IV opioids and admission to the hospital. Able to receive the first dose of rivipansel within 24 hours from administration of the first dose of IV opioids for this hospitalization. Exclusion Criteria: Non-compliance with study procedures in the double blind study (B5201002). Occurrence of any severe and/or generalized cutaneous manifestation or any other adverse event during participation in Study B5201002 that was related to study drug and which would therefore make it inappropriate for the subject to receive rivipansel in the current study. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results. Clinically significant deterioration in renal function in Study B5201002. Pregnant female subjects, breastfeeding female subjects and male and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception. Active use of illicit drugs and/or alcohol dependence.

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Includes one adult stratum (>18 years old) and one pediatric stratum (12-17 years old). Subjects aged 12 and over who weigh >40 kg, will receive a loading dose of 1680 mg followed by a maintenance dose of 840 mg. | Drug: Rivipansel<br>* Rivipansel will be infused intravenously every 12 hours up to a maximum of 15 doses.<br>* Other names: GMI-1070;|
| Experimental: Cohort 2<br>Includes one pediatric stratum (6-11 years old). Subjects 6 to 11 years of age or subjects who weigh 40 kg, will receive a loading dose of 40 mg/kg (maximum of 1680 mg) followed by a maintenance dose of 20 mg/kg (maximum of 840 mg). | Drug: Rivipansel<br>* Rivipansel will be infused intravenously every 12 hours up to a maximum of 15 doses.<br>* Other names: GMI-1070;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number (%) of subjects with treatment emergent adverse events (TEAEs) over the study. | Number (%) of subjects with treatment emergent adverse events (TEAEs) over the study, number of TEAEs over the study and rate of TEAEs per subject per Vaso-Occlusive Crisis (VOC) will be summarized overall, by system organ class and by preferred term. | 18 months | 
| Number (%) of subjects with adjudicated Acute Chest Syndrome (ACS) over the study. | Number (%) of subjects with adjudicated Acute Chest Syndrome (ACS) over the study, number of events of adjudicated ACS and the rates of these events per subject per Vaso-Occlusive Crisis (VOC) will be summarized. | 18 months | 
| Number (%) of subjects with adjudicated severe and/or generalized cutaneous manifestations over the study | Number (%) of subjects with adjudicated severe and/or generalized cutaneous manifestations over the study, number of events of adjudicated severe and/or generalized cutaneous manifestations and the rates of these events per subject per Vaso-Occlusive Crisis (VOC) will be summarized. | 18 months | 
| Number (%) of subjects with serious adverse events (SAEs) over the study. | Number (%) of subjects with serious adverse events (SAEs) over the study, number of SAEs over the study and rate of SAEs per subject per VOC will be summarized overall, by system organ class and by preferred term. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject re hospitalization | Number (%) of subjects re hospitalized for VOC within 7, 14, and 30 days of most recent discharge will be provided overall. Number of re hospitalizations for VOC within 7, 14, and 30 days of most recent discharge and the rate of re hospitalization for VOC within 7, 14, and 30 days of most recent discharge per subject per VOC will be provided as well. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCD, Rivipansel, GMI-1070, Selectin Inhibitor, VOC