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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01925001
Recruitment Status : Withdrawn (Sangart ceased operations)
First Posted : August 19, 2013
Last Update Posted : October 28, 2013
Information provided by (Responsible Party):

Tracking Information
First Submitted Date  ICMJE August 14, 2013
First Posted Date  ICMJE August 19, 2013
Last Update Posted Date October 28, 2013
Study Start Date  ICMJE October 2013
Estimated Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 16, 2013)
Duration of hospitalization for treatment of painful vaso-occlusive crisis (VOC) [ Time Frame: Up to 28 days ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2013)
  • Pain levels [ Time Frame: Up to 7 days ]
    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 ]
    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 ]
    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 ]
    Proportion of subjects with ACS complications
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 16, 2013)
  • Adverse events [ Time Frame: Up to 28 days ]
    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 ]
    Urinalysis, and biomarkers to evaluate renal function
  • Ambulation [ Time Frame: Daily up to 7 days ]
    Ability to ambulate assessed by Chair Rise and 50-foot walk tests
  • Pain diary [ Time Frame: Up to 1 year (on average) ]
    Electronic diary recording of daily pain levels using a visual analogue scale (VAS)
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE Phase 2 Study of MP4CO to Treat Vaso-occlusive Sickle Crisis
Official Title  ICMJE 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
Brief Summary

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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Anemia, Sickle Cell
  • Sickle Cell Anemia
  • Sickle Cell Disease
  • Sickle Cell Disorders
  • Hemoglobin SC Disease
  • Sickle Cell Hemoglobin C Disease
Intervention  ICMJE
  • Drug: MP4CO
    43 mg/mL pegylated carboxyhemoglobin [≥ 90% CO hemoglobin saturation] in physiological acetate electrolyte solution
    Other Names:
    • Pegylated carboxyhemoglobin
    • PEG carboxyhemoglobin
  • Drug: Sodium chloride solution
    Normal saline solution (0.9% Sodium Chloride Injection USP)
    Other Names:
    • Normal saline
    • Sodium chloride USP
    • 0.9% NaCl solution
Study Arms  ICMJE
  • Experimental: MP4CO
    Escalating doses of MP4CO, administered intravenously
    Intervention: Drug: MP4CO
  • Active Comparator: Sodium chloride solution
    Normal saline (0.9% Sodium Chloride Injection USP)administered intravenously
    Intervention: Drug: Sodium chloride solution
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: October 25, 2013)
Original Estimated Enrollment  ICMJE
 (submitted: August 16, 2013)
Estimated Study Completion Date  ICMJE October 2015
Estimated Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bahrain,   Belgium,   Brazil,   France,   Lebanon,   Netherlands,   Qatar,   Turkey,   United Kingdom
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01925001
Other Study ID Numbers  ICMJE SCD-206
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Sangart
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Sangart
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Tania Small, MD Sangart, Inc., San Diego, CA
Principal Investigator: Swee Lay Thein, MD King's College Hospital NHS Trust
PRS Account Sangart
Verification Date October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP