Sickle Cell Disease
Conditions
Keywords
Sickle Cell Disease
Brief summary
This Phase 1/Phase 2 study will evaluate GMI-1070, a pan-selectin inhibitor, in adults with stable sickle cell disease. The study will assess safety, pharmacokinetics, and microvascular effects of intravenous GMI-1070 in the outpatient setting.
Interventions
DRUGGMI-1070
Intravenous GMI-1070 given as two doses over the course of one day
Sponsors
GlycoMimetics Incorporated
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 45 years * Established diagnosis of SCD-SS or SCD-SB0-thal * At medical baseline, with no evidence of worsening of disease over the last 3 months * Available and agree to return for follow-up visits for the full duration of the study * Able to cooperate with study procedures * Documented and observed written informed consent
Exclusion criteria
* Vaso-occlusive crisis * Recent major surgery, hospitalization, infection, significant bleeding, cerebrovascular accident or seizure, or transfusion * Currently receiving, or has received within the previous 4 weeks, any other investigational agent * Pregnant or lactating female; or female of childbearing age unable or unwilling to comply with birth control or abstinence during the course of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety as Measured by the Number of Participants With Adverse Events | 28 days |
Secondary
| Measure | Time frame |
|---|---|
| Total Plasma Clearance | 48 hours |
| Volume of the Central Compartment | 48 hours |
| Intercompartmental Clearance | 48 hours |
| Volume of the Peripheral Compartment | 48 hours |
Other
| Measure | Time frame | Description |
|---|---|---|
| Blood Flow and Biomarkers of Adhesion | 48 hours | As an exploratory outcome mean change in microvascular blood flow from baseline to each time point was measured. Microvascular blood flow was also measured as microFI, perfused vessel density, and RBC velocity. |
Countries
United States
Participant flow
Recruitment details
First subject enrolled 28 May 2009; last subject completed 6 July 2010.
Participants by arm
| Arm | Count |
|---|---|
| GMI-1070 GMI-1070 administered IV at 20 mg/kg loading dose, followed by a single dose of 10 mg/kg in the evening | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | GMI-1070 |
|---|---|
| Age, Continuous | 28 years |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Safety as Measured by the Number of Participants With Adverse Events
Time frame: 28 days
Population: All enrolled subjects were analyzed for safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GMI-1070 | Safety as Measured by the Number of Participants With Adverse Events | 9 participants |
Secondary
Intercompartmental Clearance
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GMI-1070 | Intercompartmental Clearance | 31.6 mL/h/kg | Standard Deviation 17.2 |
Secondary
Total Plasma Clearance
Time frame: 48 hours
Population: All subjects were analyzed for pharmacokinetics; one subject of the 15 enrolled was lost to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GMI-1070 | Total Plasma Clearance | 19.6 mL/h/kg | Standard Deviation 6.42 |
Secondary
Volume of the Central Compartment
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GMI-1070 | Volume of the Central Compartment | 120 mL/kg | Standard Deviation 30.7 |
Secondary
Volume of the Peripheral Compartment
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GMI-1070 | Volume of the Peripheral Compartment | 64.2 mL/kg | Standard Deviation 19.6 |
Other Pre-specified
Blood Flow and Biomarkers of Adhesion
As an exploratory outcome mean change in microvascular blood flow from baseline to each time point was measured. Microvascular blood flow was also measured as microFI, perfused vessel density, and RBC velocity.
Time frame: 48 hours