Sevuparin Infusion for the Management of Acute VOC in Subjects With SCD

A Multi-Centre, Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Investigate Efficacy and Safety of Sevuparin Infusion for the Management of Acute Vaso-Occlusive Crisis (VOC) in Subjects With Sickle-Cell Disease (SCD).

A Multi-Centre, Phase II, Randomized, Double-Blind, Placebo-Controlled Study to investigate Efficacy and Safety of Sevuparin Infusion for the Management of Acute Vaso-Occlusive Crisis (VOC) in Subjects with Sickle-Cell Disease (SCD).

This will be a phase II, multi-centre, randomized, double-blind, placebo-controlled study designed to assess preliminary efficacy, safety and pharmacokinetics (PK) of 2-7 days continuous IV administration of sevuparin for the management of acute VOC in subjects with SCD.

Adults and adolescents ≥ 12 years of age will be randomized to treatment with sevuparin or placebo (ratio 1:1).

Inclusion Criteria:

• Sign a written informed consent (adults, parents) and assent (adolescents)
• Male or female, age 12-50 years.
• Diagnosis of Sickle cell disease
• Subjects admitted for an acute, painful VOC to be treated/or treated with parenteral opioid analgesia.
• Expectancy of need for hospitalization during at least 48 hours.
• Be at least 1 year postmenopausal, surgically sterile, or if Women of Child Bearing Potential (WOCBP), e.g. following menarche practicing an effective method of birth control

Exclusion Criteria:

• Severe hepatic failure/disease, abnormal liver enzyme tests or history of hepatitis B virus (HBV), hepatitis C virus (HCV)
• Abnormal conjugated (direct) bilirubin 3 fold above ULN
• History of clinically significant bleeding in vital organs
• Current clinically significant bleeding, as judged by the investigator
• Current use of acetylsalicylic acid (ASA), anti-platelet therapy, anticoagulant therapy
• Abnormal coagulation laboratory values
• A platelet count <75,000/µL.
• BMI >35
• Subjects with more than 5 hospitalizations for VOC during the last 6 months
• Evidence of acute SCD complications other than VOC at screening
• The use of strong opioids for > 3 consecutive days during the last 15 days before presenting to the hospital
• History of chronic drug abuse.
• Renal dysfunction
• Known infection (positivity) with human immunodeficiency virus (HIV), HBV or HCV.
• Significant ECG abnormality
• History of a clinically significant drug allergy to heparin, LMWH's, sevuparin, or morphine.
• Use of any investigational agent during the 30 days prior to the first dose.
• For females: pregnancy, lactating or intention of becoming pregnant
• Evidence of clinically significant disorders that might interfere with the study aim or safety of the subject
• Any condition that, in the view of the Investigator, places the subject at high risk of poor treatment compliance or of not completing the study.