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

Primary Purpose

Sickle-Cell Disease

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Sevuparin
Placebo
Sponsored by
Modus Therapeutics AB
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle-Cell Disease

Eligibility Criteria

12 Years - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Sevuparin

Arm Description

Placebo infusion

Sevuparin infusion

Outcomes

Primary Outcome Measures

Time to resolution of VOC
Time from start of infusion until resolution of VOC crisis/episode

Secondary Outcome Measures

Frequency and pattern of treatment-emergent adverse event (TEAEs)
All events to be reported from randomization until end of study
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.
Mean change in pain intensity
VAS (visual analog scale) every fourth hour. Range from 0 (no pain) to 100 (max pain)
Duration of severest pain,
Defined as time to a 30% reduction in pain intensity (VAS)
Cumulative dose of parenteral opioids
Total dose of parenteral opioids

Full Information

First Posted
July 27, 2015
Last Updated
July 15, 2019
Sponsor
Modus Therapeutics AB
Collaborators
Ergomed
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1. Study Identification

Unique Protocol Identification Number
NCT02515838
Brief Title
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

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
July 2015 (Actual)
Primary Completion Date
May 2019 (Actual)
Study Completion Date
May 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Modus Therapeutics AB
Collaborators
Ergomed

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle-Cell Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
147 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo infusion
Arm Title
Sevuparin
Arm Type
Experimental
Arm Description
Sevuparin infusion
Intervention Type
Drug
Intervention Name(s)
Sevuparin
Intervention Description
The Drug Product sevuparin solution for IV infusion
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo for IV infusion
Primary Outcome Measure Information:
Title
Time to resolution of VOC
Description
Time from start of infusion until resolution of VOC crisis/episode
Time Frame
From hospitalisation until discharge, defined as freedom from parenteral opioid use and readiness for discharge i.e. from randomisation until day 7
Secondary Outcome Measure Information:
Title
Frequency and pattern of treatment-emergent adverse event (TEAEs)
Description
All events to be reported from randomization until end of study
Time Frame
Time from start randomsiation until end of study, approximately 1 month 1 week after randomisation
Title
Pharmacokinetic (PK) characteristics of sevuparin
Description
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.
Time Frame
Pre dose, 1h, 2h, 24h, 1/day (day 3-8)
Title
Mean change in pain intensity
Description
VAS (visual analog scale) every fourth hour. Range from 0 (no pain) to 100 (max pain)
Time Frame
From baseline (visit 1) until day 3-7
Title
Duration of severest pain,
Description
Defined as time to a 30% reduction in pain intensity (VAS)
Time Frame
From baseline (visit 1) until day 3-7
Title
Cumulative dose of parenteral opioids
Description
Total dose of parenteral opioids
Time Frame
From baseline (visit 1) until day 3-7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr Bart J Biemond, MD, PhD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Salmaniya Hospital, Kingdom of Bahrain
City
Manama
Country
Bahrain
Facility Name
Salmaniya Medical Complex, Bahrain
City
Manama
Country
Bahrain
Facility Name
Annotto Bay Hospital
City
Annotto Bay
Country
Jamaica
Facility Name
Kingston Public Hospital
City
Kingston
Country
Jamaica
Facility Name
University Hospital of the West Indies
City
Kingston
Country
Jamaica
Facility Name
Winchester Surgical and Medical Institute
City
Kingston
Country
Jamaica
Facility Name
Mandeville Regional Hospital
City
Mandeville
Country
Jamaica
Facility Name
May Pen Public Hospital Clarendon
City
May Pen
Country
Jamaica
Facility Name
Cornwall Regional Hospital, Jamaica
City
Montego Bay
Country
Jamaica
Facility Name
American University of Beirut Medical Center, Beirut, Cairo street, Beirut, Lebanon
City
Beirut
Country
Lebanon
Facility Name
Nini Hospital
City
Tripoli
Country
Lebanon
Facility Name
Dept of Haematology
City
Amsterdam
Country
Netherlands
Facility Name
Erasmus MC
City
Rotterdam
Country
Netherlands
Facility Name
Sultan Qaboos University Hospital Alkhodh, Oman
City
Muscat
Country
Oman
Facility Name
Sultan Qaboos University
City
Muscat
Country
Oman
Facility Name
King Fahd Medical City, As Sulimaniyah, Riyadh Saudiarabien
City
Riyadh
Country
Saudi Arabia
Facility Name
King Saud University, Riyadh, Saudiarabien
City
Riyadh
Country
Saudi Arabia
Facility Name
Mersin University Faculty of Medicine
City
Adana
State/Province
Mersin
Country
Turkey
Facility Name
Cukurova University Faculty Of Medicine Tıp Fakültesi
City
Adana
Country
Turkey
Facility Name
Dr Antmen
City
Adana
Country
Turkey

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
33894169
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.
Results Reference
derived

Learn more about this trial

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

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