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).

Study Overview

• Status: Completed
• Conditions: Sickle-Cell Disease
• Intervention / Treatment: Other: Placebo; Drug: Sevuparin

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 Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bahrain
  • Manama, Bahrain
    • Salmaniya Hospital, Kingdom of Bahrain
  • Manama, Bahrain
    • Salmaniya Medical Complex, Bahrain
• Jamaica
  • Annotto Bay, Jamaica
    • Annotto Bay Hospital
  • Kingston, Jamaica
    • Kingston Public Hospital
  • Kingston, Jamaica
    • University Hospital of the West Indies
  • Kingston, Jamaica
    • Winchester Surgical and Medical Institute
  • Mandeville, Jamaica
    • Mandeville Regional Hospital
  • May Pen, Jamaica
    • May Pen Public Hospital Clarendon
  • Montego Bay, Jamaica
    • Cornwall Regional Hospital, Jamaica
• Lebanon
  • Beirut, Lebanon
    • American University of Beirut Medical Center, Beirut, Cairo street, Beirut, Lebanon
  • Tripoli, Lebanon
    • Nini Hospital
• Netherlands
  • Amsterdam, Netherlands
    • Dept of Haematology
  • Rotterdam, Netherlands
    • Erasmus MC
• Oman
  • Muscat, Oman
    • Sultan Qaboos University
  • Muscat, Oman
    • Sultan Qaboos University Hospital Alkhodh, Oman
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • King Fahd Medical City, As Sulimaniyah, Riyadh Saudiarabien
  • Riyadh, Saudi Arabia
    • King Saud University, Riyadh, Saudiarabien
• Turkey
  • Adana, Turkey
    • Cukurova University Faculty Of Medicine Tıp Fakültesi
  • Adana, Turkey
    • Dr Antmen
  • Mersin
    • Adana, Mersin, Turkey
      • Mersin University Faculty of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo infusion	Other: Placebo; Placebo for IV infusion
Experimental: Sevuparin; Sevuparin infusion	Drug: Sevuparin; The Drug Product sevuparin solution for IV infusion

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Modus Therapeutics AB
• Collaborators: Ergomed
• Investigators: Principal Investigator: Dr Bart J Biemond, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: July 27, 2015
• First Submitted That Met QC Criteria: August 2, 2015
• First Posted (Estimate): August 5, 2015

Study Record Updates

• Last Update Posted (Actual): July 16, 2019
• Last Update Submitted That Met QC Criteria: July 15, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: TVOC01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED