Acute Vaso-Occlusive Crisis (VOC) in Subjects with Sickle-Cell Disease MedDRA version: 20.0 Level: LLT Classification code 10040644 Term: Sickle cell disease System Organ Class: 100000004850
Conditions
Interventions
Product Name: Sevuparin
Product Code: DF02
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: sevuparin sodium
Current Sponsor code: DF02
Other descriptive name: SEVUPAR
Sponsors
Modus Therapeutics AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Sign a written informed consent (adults, parents) and assent (adolescents). 2. Male or female, age 12-50 years. 3. Diagnosis of Sickle cell disease, types HbSS, HbSC, Hb O Arab, HbSß0-thalassemia or HbSß+-thalassemia (SCD type to be confirmed by liquid chromatography or other method of comparable reliability during the study, if confirmation is not available at time of inclusion) 4. Subjects admitted for an acute, painful VOC to be treated/or treated with parenteral opioid analgesia at the time of admission. VOC is defined as an episode of pain that led to a clinic or emergency department visit, and cannot be explained except by SCD. Please note: Study treatment should start as soon as possible and at latest within 24 hours from the time of the decision to hospitalize the subject. 5. Expectancy of need for hospitalization during at least 48 hours. 6. Be at least 1 year postmenopausal, surgically sterile, or if WOCBP, e.g. following menarche practicing an effective method of birth control (e.g. oral contraception, intrauterine device, or diaphragm with spermicide; or double barrier method) during study drug administration and one month following treatment completion. Are the trial subjects under 18? yes Number of subjects for this age range: 40 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 93 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Severe hepatic failure/disease or liver enzyme tests (AST and ALT) above 2 times the upper limit of normal (ULN) range, or clinically significant impairment of liver function due to HBV, HCV or other liver diseases. 2. Conjugated (direct) bilirubin 3 fold above ULN. 3. History of clinically significant bleeding in vital organs (not due to relevant trauma), or pathological bleeding. 4. Current clinically significant bleeding, as judged by the investigator. 5. Current use of ASA, anti-platelet therapy, anticoagulant therapy and prophylactic and therapeutic LMWH or un-fractioned heparin. 6. APTT above normal range , and INR above 1.4. 7. A platelet count 35 9. Subjects with more than 5 hospitalizations for VOC during the last 6 months (to exclude subjects with exacerbations of chronic pain rather than true vaso-occlusion). 10. Evidence of acute SCD complications other than VOC at screening (CVA, ACS, multi-organ failure). 11. The use of strong opioids for > 3 consecutive days during the last 15 days before presenting to hospital. 12. History of chronic drug abuse. 13. Renal dysfunction (GFR 450 msec 16. History of a clinically significant drug allergy to heparin, LMWH’s or sevuparin. 17. Use of any investigational agent during the 30 days prior to the first dose. 18. For females: pregnancy, lactating or intention of becoming pregnant within the next 40 days. 19. Evidence of clinically significant disorders that might interfere with the study aim or safety of the subject, as judged by the Investigator: e.g. neurological, psychiatric (depression, psychosis or schizophrenia), cardiovascular (including arrhythmia), pulmonary, metabolic, gastrointestinal, endocrine diseases, coagulation or malignancies. 20. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the time to painful VOC resolution, measured from first dose given to achievement of crises resolution, as compared to placebo. ;Secondary Objective: 1. Safety+tolerability 2. Time to discharge (between 1. study drug dose and discharge) 3. Time to readiness for discharge, as judged by the subject/investigator 4. Time to discontinuation of IV opioids 5. Time from start of infusion to 25%, 50% +75% of subjects achieving VOC resolution 6. Proportion of subjects with VOC resolution achieved at 24, 48, 72, 96 and 120h 7. Clinical+subject global impression of change 8. Pain intensity assessment on VAS 9. Duration of severest pain, defined as time to a >30% reduction in VAS pain score from baseline (maintained during 8h) 10. Use of parenteral opioids (accumulated opioid consumption) 11. Use of parenteral opioids (accumulated opioid consumption as average per 24h after first dose of study drug) until VOC resolution/readiness of discharge 12. Re-occurrence of hospitalisation for VOC within 3 or 28 days from resolution of 1.VOC 13. PK of sevuparin during and after administration of sevuparin as continuous IV infusion (subgroup);Primary end point(s): Time from start of infusion until resolution of crisis/episode is defined as fulfillment of the two following criteria: a) freedom from parenteral opioid use (in preceding 8 hours) b) readiness for discharge as judged by the subject or physician ;Timepoint(s) of evaluation of this end point: at each study visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Frequency and pattern of treatment emergent adverse events (TEAEs) 2. Time to discharge (number of hours between the first study drug dose given and discharge). 3. Time to readiness for discharge, as judged by the subject or investigator (number of hours between the first study drug dose given and time point at which subjects feels readiness or investigator judges readiness for discharge from the hospital). The assessment will be done every 4 hours during time awake, starting from the time when the subject has been without parenteral opioids for 8 hours 4. Time to discontinuation of IV opioids (number of hours between the first study drug dose given and discontinuation of parenteral opioids) 5. Time from start of infusion to 25%, 50% and 75% of subjects achieving VOC resolution 6. Proportion of subjects with VOC resolution achieved at 24, 48, 72, 96 and 120 hours. 7. Clinical Global Impression of Change, measured once daily starting on day 3 until VOC resolution 8. Patient Global Impression of Change, measured once daily starting on day 3 until VOC resolution 9. Pain intensity assessment on VAS from the start of study treatment (first assessment within 30 minutes prior to infusion treatment) and thereafter every 4 hours during time awake, until VOC resolution 10. Duration of severest pain, defined as time to a 30% reduction in VAS pain score from baseline (maintained for 8 hours) 11. Amount of parenteral opioids (accumulated opioid consumption) until VOC resolution/readiness for discharge. 12. Amount of parenteral opioids (accumulated opioid consumption as average per 24h after first dose of study drug) until VOC resolution/readiness for discharge. 13. Re-occurrence of hospitalisation for VOC within 3 days, or 28 days from resolution of first VOC. 14. PK characteristics of sevuparin during and after administration of sevuparin as a continuous IV infusion (subgroup). ;Timepoint(s) of evaluation of this end point: at each study vis | — |
Countries
Bahrain, Belgium, Jamaica, Lebanon, Netherlands, Oman, Saudi Arabia, Turkey
Contacts
Public ContactMaria Klockare
Modus Therapeutics AB
Outcome results
None listed