Clinical trial NCT02515838: Sevuparin Infusion for the Management of Acute VOC in Subjects With SCD
Official title: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle-Cell Disease
Lead sponsor: Modus Therapeutics AB
Sponsor class: INDUSTRY
Collaborators: name: Ergomed
First posted: 2015-08-05
Enrollment: 147
Sex: ALL
Minimum age (years): 12
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Time to resolution of VOC
timeFrame: From hospitalisation until discharge, defined as freedom from parenteral opioid use and readiness for discharge i.e. from randomisation until day 7
Secondary outcomes:
measure: Frequency and pattern of treatment-emergent adverse event (TEAEs)
timeFrame: Time from start randomsiation until end of study, approximately 1 month 1 week after randomisation
measure: Pharmacokinetic (PK) characteristics of sevuparin
timeFrame: Pre dose, 1h, 2h, 24h, 1/day (day 3-8)
measure: Mean change in pain intensity
timeFrame: From baseline (visit 1) until day 3-7
measure: Duration of severest pain,
timeFrame: From baseline (visit 1) until day 3-7
measure: Cumulative dose of parenteral opioids
timeFrame: From baseline (visit 1) until day 3-7
Other outcomes:
Locations:
city: Manama
country: Bahrain
facility: Salmaniya Hospital, Kingdom of Bahrain
city: Manama
country: Bahrain
facility: Salmaniya Medical Complex, Bahrain
city: Annotto Bay
country: Jamaica
facility: Annotto Bay Hospital
city: Kingston
country: Jamaica
facility: Kingston Public Hospital
city: Kingston
country: Jamaica
facility: University Hospital of the West Indies
city: Kingston
country: Jamaica
facility: Winchester Surgical and Medical Institute
city: Mandeville
country: Jamaica
facility: Mandeville Regional Hospital
city: May Pen
country: Jamaica
facility: May Pen Public Hospital Clarendon
city: Montego Bay
country: Jamaica
facility: Cornwall Regional Hospital, Jamaica
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center, Beirut, Cairo street, Beirut, Lebanon
city: Tripoli
country: Lebanon
facility: Nini Hospital
city: Amsterdam
country: Netherlands
facility: Dept of Haematology
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Muscat
country: Oman
facility: Sultan Qaboos University Hospital Alkhodh, Oman
city: Muscat
country: Oman
facility: Sultan Qaboos University
city: Riyadh
country: Saudi Arabia
facility: King Fahd Medical City, As Sulimaniyah, Riyadh Saudiarabien
city: Riyadh
country: Saudi Arabia
facility: King Saud University, Riyadh, Saudiarabien
city: Adana
country: Turkey
facility: Mersin University Faculty of Medicine
state: Mersin
city: Adana
country: Turkey
facility: Cukurova University Faculty Of Medicine Tıp Fakültesi
city: Adana
country: Turkey
facility: Dr Antmen
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Dr Bart J Biemond, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Biemond BJ, Tombak A, Kilinc Y, Al-Khabori M, Abboud M, Nafea M, Inati A, Wali Y, Kristensen J, Kowalski J, Donnelly E, Ohd J; TVOC01 Investigators Group. Sevuparin for the treatment of acute pain crisis in patients with sickle cell disease: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Haematol. 2021 May;8(5):e334-e343. doi: 10.1016/S2352-3026(21)00053-3.