Safety Study of MP4CO in Adult Sickle Cell Patients

NCT01356485 | Completed Phase 1 DMC

• 1 other identifier: SCD-105
• Study Type: interventional
• Target: 32
• Locations: 4 countries
• Sites: 5

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.

Conditions

Anemia, Sickle Cell; Sickle Cell Anemia; Sickle Cell Disease; Sickle Cell Disorders; Hemoglobin SC Disease; Sickle Cell Hemoglobin C Disease

Keywords

Sickle cell anemia; Sickle cell disease; Sickling crisis; Vaso-occlusive crisis; Carboxyhemoglobin; Oxygen therapeutic; Hemoglobin solutions; Pegylated hemoglobin

Outcome Measures

Primary Outcomes (1)

• No efficacy evaluations will be made in this safety study

  28 days

Secondary Outcomes (5)

• Adverse events

  From 0 hrs after dosing through 28 Day Follow-up visit

• Vital signs

  Baseline, Hourly from 0 - 8 hours, 24, 48, and 72 hours, and at 7 days

• Laboratory assessments

  Baseline, 24, 48, and 72 hours, and at 7 days

• Pain levels

  Baseline, Hourly from 0 - 8 hours, 24, 48, and 72 hours, and at 7 days

• Pulmonary artery pressure assessment

  Baseline, Pre-infusion, 1 hour post-infusion

Study Arms (2)

MP4CO

EXPERIMENTAL

Escalating doses of MP4CO, administered intravenously

Drug: MP4CO

Saline

PLACEBO COMPARATOR

Normal saline (0.9% sodium chloride solution)

Drug: Sodium chloride solution

Interventions

MP4CO DRUG

43 mg/mL pegylated carboxyhemoglobin \[≥ 90% CO hemoglobin saturation\] in physiological acetate electrolyte solution

Also known as: Pegylated carboxyhemoglobin, PEG carboxyhemoglobin

MP4CO

Sodium chloride solution DRUG

Normal saline (0.9% sodium chloride solution)

Also known as: Normal saline, Sodium chloride, 0.9% NaCL solution

Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male or female patients (18 years of age or older) with diagnosed sickle cell disease based on Hb SS, or S/β0 Thalassemia genotype, who are clinically stable and not experiencing an acute episode of pain

You may not qualify if:

• At least 4 painful VOCs within the preceding year requiring hospital treatment
• Urgent care facility, hospital treatment or admission for treatment of a painful VOC within the previous 2 months
• History of a painful VOC lasting longer than 2 weeks or \> 12 pain episodes requiring intervention in a medical facility (emergency room, urgent care or clinic) in preceding year
• Baseline VAS pain score ≥ 4 cm
• Hemoglobin \< 6 g/dL
• Transfusion of packed red blood cells within previous 4 weeks
• Currently on iron chelation therapy
• History of sickle cell disease-attributed CNS disease (including a) recent or past history of stroke; b) ongoing treatment with chronic transfusion therapy to prevent stroke; c. history of seizures or epilepsy; and d. evidence of or known overt cerebral vasculopathy or known cerebral vessel narrowing
• Evidence of pulmonary hypertension, based on an estimated systolic pulmonary artery pressure \> 25 mmHg calculated from TRJ velocity from a transthoracic echocardiography (TTE) assessment at Screening visit or from a previous TTE assessment if it was done within 1 year prior to randomization
• Baseline oxygen saturation by pulse oximetry ≤ 90%
• History of a priapism within the last year
• History of hypertension requiring anti-hypertensive therapy
• Baseline bradycardia (heart rate \< 60/min)
• History of myocardial infarction, myocardial ischemia, or angina
• Renal dysfunction or creatinine level within past 6 weeks of ≥ 1.2 mg/dL (≥ 106 µmol/L) or a urine protein/creatinine ratio (PCR) \> 50 mg/mmol

Sponsors & Collaborators

• Sangart: lead

Study Sites (5)

Hôpital Henri Mondor

Créteil, France

Location

Sickle Cell Unit, University of West Indies

Kingston, Jamaica

Location

Rafic Hariri University Hospital

Beirut, Lebanon

Location

Guy's Hospital

London, United Kingdom

Location

King's College London

London, United Kingdom

Location

Related Links

• Sangart, Inc. (Home page)

MeSH Terms

Conditions

Anemia, Sickle Cell; Hemoglobin SC Disease; Vaso-Occlusive Crises

Interventions

PEGylated carboxyhemoglobin bovine; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Tania Small, MD

  Sangart, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2011
• First Posted: May 19, 2011
• Study Start: January 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: August 19, 2013

Record last verified: 2013-08

Locations

GB (2); LE (1); FR (1); JA (1)