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

Study Overview
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Brief Summary
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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).

Detailed Description
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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).

Official Title
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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).

Conditions
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Sickle-Cell Disease

Intervention / Treatment
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* Drug: Sevuparin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo infusion | Other: Placebo<br>* Placebo for IV infusion<br>|
| Experimental: Sevuparin<br>Sevuparin infusion | Drug: Sevuparin<br>* The Drug Product sevuparin solution for IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to resolution of VOC | Time from start of infusion until resolution of VOC crisis/episode | From hospitalisation until discharge, defined as freedom from parenteral opioid use and readiness for discharge i.e. from randomisation until day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and pattern of treatment-emergent adverse event (TEAEs) | All events to be reported from randomization until end of study | Time from start randomsiation until end of study, approximately 1 month 1 week after randomisation | 
| Pharmacokinetic (PK) characteristics of sevuparin | PK characteristics of sevuparin during and after administration of sevuparin as a continuous IV infusion (subgroup) ◦Area under the plasma concentration versus time curve (AUC) of Sevuparin. | Pre dose, 1h, 2h, 24h, 1/day (day 3-8) | 
| Mean change in pain intensity | VAS (visual analog scale) every fourth hour. Range from 0 (no pain) to 100 (max pain) | From baseline (visit 1) until day 3-7 | 
| Duration of severest pain, | Defined as time to a 30% reduction in pain intensity (VAS) | From baseline (visit 1) until day 3-7 | 
| Cumulative dose of parenteral opioids | Total dose of parenteral opioids | From baseline (visit 1) until day 3-7 |