Safety and Pharmacokinetics of SANGUINATE™ in Sickle Cell Disease (SCD) Patients

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2013 by Prolong Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Prolong Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01374165
First received: May 26, 2011
Last updated: April 23, 2013
Last verified: April 2013
  Purpose

Prolong proposes to test safety, tolerability and pharmacokinetics of SANGUINATE™ in sickle cell disease (SCD) patients. Prolong's preclinical studies showed that SANGUINATE™ was safe in a number of different animal models and toxicology studies. In this Phase I trial, Prolong will test whether it is also safe and tolerable in sickle cell patients. The study will be conducted in 15 adult (>18 years) patients.


Condition Phase
Sickle Cell Disease
Phase 1

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Phase I Open Label, Unblinded, Single Dose Study for Evaluating the Safety and Pharmacokinetics of SANGUINATE™ in Sickle Cell Disease (SCD) Patients

Resource links provided by NLM:


Further study details as provided by Prolong Pharmaceuticals:

Primary Outcome Measures:
  • Evaluate the safety and tolerability of two dose regimen for SANGUINATE™ in sickle cell disease patients [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]

    The following assessments will be used to evaluate the safety of SANGUINATE™ administration:

    • adverse events, serious adverse events
    • laboratory abnormalities by highest toxicity grade
    • laboratory abnormalities by largest increase in toxicity grade from baseline


Secondary Outcome Measures:
  • Determine the plasma pharmacokinetic (PK) profile of SANGUINATE™ in sickle cell disease patients. Mean values by treatment received will be calculated for the following PK parameters for PEGylated bovine hemoglobin: [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
    • Cmax -the maximum measured plasma concentration
    • tmax -the time to reach maximum plasma concentration
    • AUC0-last -the area under the plasma concentration versus time curve from time zero to the time of the last measurable plasma concentration, calculated by the linear or log/linear trapezoidal method
    • AUC0-inf -the area under the plasma concentration versus time curve from time zero to infinity, calculated as: AUCinf = AUCt + (Ct/Kel), where Ct = the last measurable concentration
    • λz -the apparent elimination rate constant
    • t1/2 -the terminal half-life
    • CV -coefficient of variation


Biospecimen Retention:   Samples Without DNA

Whole blood and urine


Estimated Enrollment: 15
Groups/Cohorts
Low dose SANGUINATE™

160 mg/kg of SANGUINATE™.

SANGUINATE™ (PEG-bHb-CO) an OTA is composed of three moieties, polyethylene glycol, bHb and carbon monoxide that act in a specific manner to promote the delivery of oxygen to tissue. SANGUINATE™ was not developed to be used as a blood substitute. It is instead an oxygen transfer agent intended to functionally deliver and release oxygen to hypoxic tissues.

High dose of SANGUINATE™

320 mg/kg of SANGUINATE™.

SANGUINATE™ (PEG-bHb-CO) an OTA is composed of three moieties, polyethylene glycol, bHb and carbon monoxide that act in a specific manner to promote the delivery of oxygen to tissue. SANGUINATE™ was not developed to be used as a blood substitute. It is instead an oxygen transfer agent intended to functionally deliver and release oxygen to hypoxic tissues.


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Sickle Cell Disease (SCD) patients

Criteria

Eligibility Criteria:

Sickle cell patients will be enrolled and will be selected based on:

Inclusion:

  1. Patients must understand and be willing to give written informed consent prior to any study procedures or evaluations and be willing to adhere to all study schedules and requirements.
  2. Hb levels: > 6 gr/dl - <10 gr/dl;
  3. Age: > 18 - 65 years;
  4. Body Mass Index ≥20 and ≤30 kg/m2;
  5. Documented 12-lead ECG with no clinically significant abnormalities, as determined by the Investigator;
  6. Female subjects of reproductive potential must have a negative serum pregnancy (β-HCG) test at screening and a negative urine pregnancy test at Day 0 prior to dosing. Female subjects must also be non-lactating;
  7. Adequate venous access and can receive intravenous infusions;
  8. Frequency of ER hospitalizations < 6x/yr for SCD pain events documented "medical history".

Exclusion:

  1. In medical opinion of investigator, the patient is not an appropriate candidate;
  2. Patient is infected;
  3. The patient is Febrile;
  4. Patient has Acute chest syndrome or documented Sickle Cell Crisis;
  5. Patient with hemoglobin above 10gr/dl or below 6 gm/dl
  6. If female, pregnant or lactating;
  7. History of clinically significant disease, as determined by the Investigator;
  8. History of allergy or major allergic reaction considered to be clinically significant by the Investigator;
  9. Physical examination or 12-lead ECG result(s) considered to be clinically significant by the Investigator;
  10. Received or intending to receive a vaccination in the two weeks prior to dosing, or anytime during study participation;
  11. Unable to comply with study attendance, protocol procedures or other study requirements;
  12. Frequency of ER hospitalizations > 6x/yr for SCD pain events;
  13. Patient has Renal or liver dysfunction;
  14. Patient has Severe pulmonary hypertension (index > 3 meters per sec based on documented Echocardiograph);
  15. Any history of significant cardiac, renal, neurologic, metabolic, pulmonary, gastrointestinal, chronic hepatic disease or any other disease which in the judgment of the investigator would interfere with the study or confound the results;
  16. Screening laboratory result indicating HIV-positivity, or previously diagnosed with AIDS, AIDS related complex, or other immunodeficiency;
  17. Screening laboratory result indicating serologic positivity for hepatitis C antibodies or hepatitis B surface antigens, unless explained by a documented vaccination.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01374165

Contacts
Contact: Benjamin Brenner, Prof 972 4 8543520 b_brenner@rambam.health.gov.il

Locations
Israel
Rambam Health Care Campus Not yet recruiting
Haifa, Israel
Contact: Benjamin Brenner, Prof.    972 4 8543520    b_brenner@rambam.health.gov.il   
Sub-Investigator: Nagib Dali, Dr.         
Sub-Investigator: Evelyne Shabad, Dr.         
Sponsors and Collaborators
Prolong Pharmaceuticals
  More Information

No publications provided

Responsible Party: Prolong Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01374165     History of Changes
Other Study ID Numbers: SCIL-SANG-001
Study First Received: May 26, 2011
Last Updated: April 23, 2013
Health Authority: Israel: Ministry of Health

Keywords provided by Prolong Pharmaceuticals:
SCD

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on August 20, 2014