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

Phase 2

Completed

• Conditions: Sickle-Cell Disease
• Interventions: Other: Placebo; Drug: Sevuparin

• Registration Number: NCT02515838
• Lead Sponsor: Modus Therapeutics AB

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).

Study Timeline

• Study Start: 2015-07
• Study First Submitted: 2015-07-27
• Study First Submitted QC: 2015-08-02
• Study First Posted: 2015-08-05
• Status Verified: 2019-02
• Primary Completion: 2019-05
• Study Completion: 2019-05
• Last Update Submitted: 2019-07-15
• Last Update Posted: 2019-07-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 147

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo infusion
Sevuparin	Sevuparin	Sevuparin infusion

Primary Outcome Measures

Name	Time	Method
Time to resolution of VOC	From hospitalisation until discharge, defined as freedom from parenteral opioid use and readiness for discharge i.e. from randomisation until day 7	Time from start of infusion until resolution of VOC crisis/episode

Secondary Outcome Measures

Name	Time	Method
Duration of severest pain,	From baseline (visit 1) until day 3-7	Defined as time to a 30% reduction in pain intensity (VAS)
Cumulative dose of parenteral opioids	From baseline (visit 1) until day 3-7	Total dose of parenteral opioids
Frequency and pattern of treatment-emergent adverse event (TEAEs)	Time from start randomsiation until end of study, approximately 1 month 1 week after randomisation	All events to be reported from randomization until end of study
Pharmacokinetic (PK) characteristics of sevuparin	Pre dose, 1h, 2h, 24h, 1/day (day 3-8)	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.
Mean change in pain intensity	From baseline (visit 1) until day 3-7	VAS (visual analog scale) every fourth hour. Range from 0 (no pain) to 100 (max pain)

Trial Locations

Locations (20)

Kingston Public Hospital; 🇯🇲 Kingston, Jamaica

Winchester Surgical and Medical Institute; 🇯🇲 Kingston, Jamaica

Mandeville Regional Hospital; 🇯🇲 Mandeville, Jamaica

May Pen Public Hospital Clarendon; 🇯🇲 May Pen, Jamaica

American University of Beirut Medical Center, Beirut, Cairo street, Beirut, Lebanon; 🇱🇧 Beirut, Lebanon

Cornwall Regional Hospital, Jamaica; 🇯🇲 Montego Bay, Jamaica

Nini Hospital; 🇱🇧 Tripoli, Lebanon

Dept of Haematology; 🇳🇱 Amsterdam, Netherlands

Sultan Qaboos University Hospital Alkhodh, Oman; 🇴🇲 Muscat, Oman

Erasmus MC; 🇳🇱 Rotterdam, Netherlands

Mersin University Faculty of Medicine; 🇹🇷 Adana, Mersin, Turkey

University Hospital of the West Indies; 🇯🇲 Kingston, Jamaica

King Fahd Medical City, As Sulimaniyah, Riyadh Saudiarabien; 🇸🇦 Riyadh, Saudi Arabia

King Saud University, Riyadh, Saudiarabien; 🇸🇦 Riyadh, Saudi Arabia

Cukurova University Faculty Of Medicine Tıp Fakültesi; 🇹🇷 Adana, Turkey

Dr Antmen; 🇹🇷 Adana, Turkey

Salmaniya Hospital, Kingdom of Bahrain; 🇧🇭 Manama, Bahrain

Salmaniya Medical Complex, Bahrain; 🇧🇭 Manama, Bahrain

Annotto Bay Hospital; 🇯🇲 Annotto Bay, Jamaica

Sultan Qaboos University; 🇴🇲 Muscat, Oman