Clinical Trial: Safety Study of MP4CO in Adult Sickle Cell Patients

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multi-center, Randomized, Double Blind, Dose Escalation Safety Study of MP4CO in Clinically Stable Adult Sickle Cell Patients

Brief Summary:

Sickle Cell Anemia 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 in the circulatory system, the deoxygenated abnormal hemoglobin S can begin to polymerize. When this occurs, the red blood cells can become sticky and elongated. These sickled red blood cells are less flexible and will obstruct small blood vessels and block normal red blood cells from traveling through the circulatory system, which limits oxygen delivery to tissues and organs. This is known as a "sickle crisis".

Patients suffering from a sickle crisis experience severe pain and are at risk of stroke, heart attack or even death. By lowering the level of oxygen pressure at which sickling occurs and opening the vasculature and rapidly delivering oxygen directly to ischemic tissues, the addition of MP4CO to existing treatment protocols may alleviate pain associated with a sickle cell crisis, abort a crisis and/or potentially reduce the duration of a crisis. This could mean less time in the hospital and an improved quality of life for patients with sickle cell anemia.

Detailed Summary:

To date, no specific agent has been approved to treat sickle cell crisis, to reduce the severity of a sickling crisis, or to shorten the duration of admission. Current therapy for a sickling 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. Carbon monoxide (CO) binds to Hb S and, while attached, prevents and reverses polymerization of Hb S chains and consequent distortion of the red blood cell. Carbon monoxide at very low doses also acts as a messenger to cells, reducing inflammation, reducing oxygen requirements, and preventing programmed cell death (apoptosis).

The MP4 molecule can be modified to carry CO and other gases to enhance therapeutic benefit for certain patients. MP4CO is therefore designed to deliver therapeutic, non-toxic levels of CO, to provide an immediate metabolic signal to cells and to reduce inflammation. Once the CO is released from the compound, the MP4 molecule gets oxygenated in the lung and then delivers oxygen to ischemic tissues.

Previously published studies provide a good foundation to postulate that a chemically modified hemoglobin such as MP4CO might have the ideal properties as an oxygen therapeutic agent for treatment or reversal of a sickling crisis. The initial release of CO from MP4CO is predicted to have a therapeutic effect including immediate stabilization of Hb S to prevent further polymerization and reverse existing sickling, vasodilation of capillaries, and anti-inflammatory properties. The subsequent circulation of the MP4 molecule as an oxygen therapeutic agent (after converting to MP4OX following oxygenation in the lungs) will help to 1) preferentially oxygenate ischemic cells, 2) reverse partially sickled red cells, and 3) impro
Sponsor: Sangart

Current Primary Outcome: No efficacy evaluations will be made in this safety study [ Time Frame: 28 days ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Adverse events [ Time Frame: From 0 hrs after dosing through 28 Day Follow-up visit ]
• Vital signs [ Time Frame: Baseline, Hourly from 0 - 8 hours, 24, 48, and 72 hours, and at 7 days ]
  Blood pressure, heart rate, respiration, temperature
• Laboratory assessments [ Time Frame: Baseline, 24, 48, and 72 hours, and at 7 days ]
  Hematology, serum chemistry, urinalysis, renal function and biomarkers
• Pain levels [ Time Frame: Baseline, Hourly from 0 - 8 hours, 24, 48, and 72 hours, and at 7 days ]
  Patient self-assessment of pain levels using Visual Analogue Scale
• Pulmonary artery pressure assessment [ Time Frame: Baseline, Pre-infusion, 1 hour post-infusion ]
  Trans-thoracic Echocardiography (TTE)

Original Secondary Outcome:

• Adverse events [ Time Frame: From 0 hrs after dosing through 28 Day Follow-up visit ]
• Vital signs [ Time Frame: Baseline, Hourly from 0 - 8 hours, 24, 48, and 72 hours, and at 7 days ]
  Blood pressure, heart rate, respiration, temperature
• Laboratory assessments [ Time Frame: Baseline, 24, 48, and 72 hours, and at 7 days ]
  Hematology, serum chemistry, urinalysis, renal function and biomarkers
• Pain levels [ Time Frame: Baseline, Hourly from 0 - 8 hours, 24, 48, and 72 hours, and at 7 days ]
  Patient self-assessment of pain levels using Visual Analogue Scale

Information By: Sangart

Dates:
Date Received: May 17, 2011
Date Started: January 2012
Date Completion:
Last Updated: August 15, 2013
Last Verified: August 2013