Clinical trial NCT01119833 (phase 2, status: completed)
Conditions: sickle cell disease, vaso-occlusive crisis, pain crisis
ICD codes: D57.1, D57.20, D57.212, D57.219, D57.211, D57.213, D57.218
Drugs: gmi-1070, placebo
SMILES: [H][C@@](CC1CCCCC1)(O[C@H]1[C@@H](O)[C@@H](CO)O[C@@H](O[C@@H]2C[C@@H](C[C@H](NC(=O)C3=CC(=O)NC(=O)N3)[C@H]2O[C@@H]2O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]2O)C(=O)NCCNC(=O)COCCOCC(=O)NC2=C3C(=CC(=C2)S(O)(=O)=O)C=C(C=C3S(O)(=O)=O)S(O)(=O)=O)[C@@H]1OC(=O)C1=CC=CC=C1)C(O)=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          1. 12 to 60 years of age

          2. Confirmed diagnosis of sickle cell disease (HbSS or HbS-β0thalassemia)

          3. Diagnosis of VOC at the time of enrollment

          4. Hospitalized or in process of admission at the time of enrollment

          5. Able to receive the first dose of study drug within 24 hours of initial medical
             evaluation in the Emergency Department/clinic for VOC;

             o Subjects treated as an outpatient within the past 48 hours for the same VOC episode
             may be enrolled if dosing is also expected within 24 hours of their second (admitting)
             presentation.

          6. Documented and observed written informed consent (and assent, where applicable)

        Exclusion Criteria:

          1. Infection, diagnosed or strongly suspected, as evidenced by one or more of the
             following:

               -  Fever >39°C (102.2°F)

               -  In the presence of fever ≥38.5°C (101.3°F), 1 of the following:

                    -  Positive findings (suspicious for infection) on diagnostic tests, such as
                       cerebral spinal fluid [CSF] evaluation, radiographs, or bacterial culture of
                       normally sterile sites

                    -  Exam findings leading to diagnosed or strongly suspected bone or joint
                       infection

                    -  Determination by physician that bacterial or serious systemic viral
                       infection is likely (eg, influenza, mononucleosis)

                    -  Subjects may be included with uncomplicated urinary tract infections
                       (provided they do not have fever ≥38.5° C [101.3° F] or costo-vertebral
                       angle [CVA] tenderness), and/or suspected minor viral syndromes (upper
                       respiratory infection symptoms but no symptoms suggestive of bacterial
                       infection other than uncomplicated otitis media or uncomplicated
                       streptococcal pharyngitis)

          2. Acute chest syndrome, diagnosed or strongly suspected, as evidenced by a new
             infiltrate on chest radiograph, and 1 or more of the following:

               -  Fever >39° C (102.2° F)

               -  Hypoxia (confirmed by arterial blood gases [ABG] with paO2 <70 mmHg)

               -  Chest pain

               -  Suspicious findings on exam (tachypnea, intercostal retractions, wheezing, and/or
                  rales)

          3. Sickle cell disease (SCD) pain atypical of VOC, including hepatic or splenic
             sequestration, cholecystitis, or pneumonia.

          4. Acute stroke, acute priapism, severe avascular necrosis of the hip/shoulder when the
             presenting pain is only in the affected hip/shoulder

          5. Serum creatinine:

               -  >1.2 mg/dL for subjects 16 to 60 years of age

               -  >1.0 mg/dL for subjects 12 to 15 years of age

          6. Alanine transaminase (ALT/SGPT) >2x upper limit of normal (ULN) (based on clinic
             laboratory normal range)

          7. Hemoglobin <5 g/dL

          8. Platelets <100,000/mm3

          9. Recent (within the past 30 days) major surgery, hospitalization for other than VOC,
             documented serious bacterial infection requiring antibiotic treatment, or significant
             bleeding

         10. Hospitalization for uncomplicated VOC, or treated with parenteral pain medications in
             other medical settings such as the emergency department or day hospital for
             uncomplicated VOC, within past 14 days.

             o Subjects may be included if treated as an outpatient within the past 48 hours for
             the same VOC episode.

         11. Recent (within the past 90 days) cerebrovascular accident, transient ischemic attack,
             or seizure

         12. pRBC transfusions in the past 14 days

         13. Systemic steroid therapy within 48 hours prior to enrollment or expectation that
             therapy may be used during the study (inhaled or topical steroids are allowed)

         14. For those on chronic or long-acting opioids, a change in dose in the past 14 days OR
             pain requiring medical attention in the past 14 days (change in opioid medication for
             acute pain in the past 48 hours and directly related to this VOC admission is allowed)

         15. Greater than 5 episodes of hospitalization for VOC in the past 6 months (180 days)

         16. Medical or psychiatric condition that, in the opinion of the investigator, may pose a
             risk to the subject for participation or interfere with the conduct or results of the
             study

         17. Currently receiving, or has received within the previous 4 weeks, any other
             investigational agent

         18. Previous administration of GMI-1070

         19. Expectation that the subject will not be able to be followed for the duration of the
             study

         20. Pregnant or lactating female; or female of childbearing potential or male unable or
             unwilling to comply with birth control methods or abstinence during the course of the
             study

         21. Active use of illicit drugs and/or alcohol dependence, as determined by the
             investigator