Sickle Cell Disease Clinical Trial
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
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.
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.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
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