Phase 2 Study of MP4CO to Treat Vaso-occlusive Sickle Crisis

This study has been withdrawn prior to enrollment.
(Sangart ceased operations)
Sponsor:
Information provided by (Responsible Party):
Sangart
ClinicalTrials.gov Identifier:
NCT01925001
First received: August 14, 2013
Last updated: October 25, 2013
Last verified: October 2013
  Purpose

Sickle Cell disease is caused by an inherited hemoglobin disorder. Healthy red blood cells are discoid and can deform and move through small blood vessels to carry oxygen to all parts of the body. In Sickle Cell disease, as red blood cells circulate and oxygen is released, the deoxygenated abnormal Hemoglobin S can begin to polymerize and cause red cells to become sticky and elongated. These "sickled" red cells are less flexible and will obstruct small blood vessels and prevent normal red cells from circulating freely, which limits oxygen delivery to tissues and organs. This is known as a "sickling crisis" or "vaso-occlusive crisis" and is the leading cause of hospitalization in patients with Sickle Cell disease.

Patients suffering from a sickle crisis experience severe pain and are at risk of stroke, heart attack or even death. Current therapy is limited to hydration and symptomatic pain relief. The administration of MP4CO as an adjunct treatment to standard therapy may alleviate pain associated with a sickling crisis and potentially reduce the severity and duration of a crisis. This may shorten the time in hospital and potentially improve the quality of life for patients with sickle cell anemia.


Condition Intervention Phase
Anemia, Sickle Cell
Sickle Cell Anemia
Sickle Cell Disease
Sickle Cell Disorders
Hemoglobin SC Disease
Sickle Cell Hemoglobin C Disease
Drug: MP4CO
Drug: Sodium chloride solution
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Multi-center, Randomized, Double-blind, Comparator-Controlled Dose Finding Study to Evaluate MP4CO for the Acute Treatment of Vaso-occlusive Crises in Subjects With Sickle Cell Disease

Resource links provided by NLM:


Further study details as provided by Sangart:

Primary Outcome Measures:
  • Duration of hospitalization for treatment of painful vaso-occlusive crisis (VOC) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Time from randomization to resolution of the vaso-occlusive crisis, assessed by evaluation of cessation of opioid analgesia, recovery of ambulation, and/or ready for hospital discharge.


Secondary Outcome Measures:
  • Pain levels [ Time Frame: Up to 7 days ] [ Designated as safety issue: No ]
    Proportion of subjects with a pre-defined reduction in pain levels assessed using a visual analogue scale (VAS)

  • Readmission to emergency room (ER) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Proportion of subjects with at least one return visit to ER after hospital discharge

  • Re-admission to hospital for treatment of VOC [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Proportion of subjects re-admitted to hospital for VOC treatment within 7 days after discharge

  • Acute Chest Syndrome (ACS) complications [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
    Proportion of subjects with ACS complications


Other Outcome Measures:
  • Adverse events [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
    Adverse events (AEs) assessed daily through 7 days, and Serious Adverse Events (SAEs) throughout Day 28 follow-up visit

  • Urine biomarkers [ Time Frame: Up to 7 days ] [ Designated as safety issue: Yes ]
    Urinalysis, and biomarkers to evaluate renal function

  • Ambulation [ Time Frame: Daily up to 7 days ] [ Designated as safety issue: No ]
    Ability to ambulate assessed by Chair Rise and 50-foot walk tests

  • Pain diary [ Time Frame: Up to 1 year (on average) ] [ Designated as safety issue: No ]
    Electronic diary recording of daily pain levels using a visual analogue scale (VAS)


Enrollment: 0
Study Start Date: October 2013
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MP4CO
Escalating doses of MP4CO, administered intravenously
Drug: MP4CO
43 mg/mL pegylated carboxyhemoglobin [≥ 90% CO hemoglobin saturation] in physiological acetate electrolyte solution
Other Names:
  • Pegylated carboxyhemoglobin
  • PEG carboxyhemoglobin
Active Comparator: Sodium chloride solution
Normal saline (0.9% Sodium Chloride Injection USP)administered intravenously
Drug: Sodium chloride solution
Normal saline solution (0.9% Sodium Chloride Injection USP)
Other Names:
  • Normal saline
  • Sodium chloride USP
  • 0.9% NaCl solution

Detailed Description:

Sickle cell disease (SCD) is an autosomal recessive disorder of the β globin gene of the hemoglobin molecule. To date, no specific agent has been approved to treat a sickle cell crisis, to reduce the severity of a sickling crisis, or to shorten the duration of admission. Current therapy for a crisis is limited to hydration and symptomatic pain relief with opiates when pain is severe enough to cause admission to hospital. Administration of oxygen by inhalation alone has not proven effective. The carbon monoxide (CO) molecule binds to Hb S and, while attached, prevents and reverses polymerization of Hb S chains and the distortion of the red cell. CO at very low doses also acts as a cell-signaling molecule, and may reduce inflammation, decrease oxygen requirements, and prevent programmed cell death (apoptosis).

MP4CO is designed as an ischemic rescue therapy to deliver non-toxic levels of CO, to provide an immediate metabolic signal to cells to help reverse red cell sickling, and to reduce inflammation.

Previously published studies provide a foundation to postulate that MP4CO might have the appropriate properties for treatment or reversal of an acute sickling crisis. The initial release of CO from MP4CO is predicted to have a beneficial effect including immediate stabilization of Hb S to prevent further red cell polymerization and reverse existing sickling, dilation of capillaries to enhance tissue perfusion, and anti-inflammatory cell-signalling properties. The subsequent circulation of the MP4 molecule as an oxygen therapeutic (after converting to MP4OX following oxygenation in the lungs) will help to 1) preferentially oxygenate ischemic tissue, 2) reverse partially sickled red cells, and 3) improve perfusion and oxygenation of local tissues to potentially ameliorate the painful crisis caused by sickling of red cells. In addition, MP4CO has enhanced chemical stability, which enables storage at room temperature.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed Informed Consent (and assent as required for minors)
  • Diagnosis of SCD (known HbSS or HbSß0)
  • Sixteen years of age or older
  • Prior history of at least one VOC requiring hospitalization within the last 24 months

Exclusion Criteria:

  • ≥ 5 VOCs within the preceding 6 months requiring Emergency Room (ER) visits or hospital admissions
  • History of overt stroke or cerebral vascular accident within the previous 12 months
  • Remained in the hospital for ≥2 weeks (14 days) for VOC management within the previous 6 months
  • Known pulmonary hypertension based on an estimated tricuspid regurgitant jet velocity (TRJV) >2.90 m/s or definitive diagnosis by prior right heart catheterization
  • Baseline SaO2 level by pulse oximetry <92% on room air
  • Systemic hypertension (baseline systolic pressure ≥ 160 mmHg or diastolic pressure ≥ 90 mmHg)
  • History of myocardial infarction, myocardial ischemia, or angina
  • On a chronic red blood cell transfusion therapy program (simple or exchange)
  • Renal dysfunction presenting with a GFR<60 mL/min/1.73m
  • Any diagnosis of a concurrent chronic debilitating disease that may affect the completion of the study or results of the study as determined by the investigator
  • Currently enrolled in any other investigational treatment study
  • Significant substance abuse.
  • Known to have HIV, active hepatitis B, or C infection, or active tuberculosis
  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: NCT01925001

Locations
Bahrain
Salmaniya Medical Complex
Manama, Bahrain
Belgium
University Hospital Brugmann
Brussels, Belgium
Brazil
Rio de Janerio Instituto Estadual de Hematologie
Rio de Janerio, Brazil
France
Hôpital Henri Mondor
Créteil, France
Georges Pompidou European University Hospital
Paris, France
Lebanon
Univ. Medical Center Rizk Hospital
Beirut, Lebanon
American Univ. of Beirut Medical Center
Beirut, Lebanon
Netherlands
Academic Medical Center
Amsterdam, Netherlands
Qatar
Cornell Medical City
Doha, Qatar
Turkey
Cukurova University Medical Facilty
Adana, Turkey
Mersin University Medical Faculty
Mersin, Turkey
United Kingdom
King's College Hospital
London, United Kingdom
Guys Hospital
London, United Kingdom
Queen Mary Hospital
London, United Kingdom
Sponsors and Collaborators
Sangart
Investigators
Study Director: Tania Small, MD Sangart, Inc., San Diego, CA
Principal Investigator: Swee Lay Thein, MD King's College Hospital NHS Trust
  More Information

Additional Information:
Publications:

Responsible Party: Sangart
ClinicalTrials.gov Identifier: NCT01925001     History of Changes
Other Study ID Numbers: SCD-206
Study First Received: August 14, 2013
Last Updated: October 25, 2013
Health Authority: Bahrain: Ethics Committee
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: National Health Surveillance Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Lebanon: Ministry of Public Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Oman: Academic Accreditation Authority
Qatar: Hamad Medical Corporation
Saudi Arabia: Ministry of Health
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Sangart:
Sickle cell anemia
Sickle cell disease
Sickling crisis
Vaso-occlusive crisis
Carboxyhemoglobin
Oxygen therapeutic
Ischemic rescue therapy
Hemoglobin solution
Pegylated hemoglobin

Additional relevant MeSH terms:
Hemoglobin C Disease
Anemia
Anemia, Sickle Cell
Hemoglobin SC Disease
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014