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

• ClinicalTrials.gov Identifier: NCT02515838
• Recruitment Status: Completed
• First Posted: August 5, 2015
• Last Update Posted: July 16, 2019
• Sponsor: Modus Therapeutics AB
• Collaborator: Ergomed
• Information provided by (Responsible Party): Modus Therapeutics AB

Tracking Information

• First Submitted Date: July 27, 2015
• First Posted Date: August 5, 2015
• Last Update Posted Date: July 16, 2019
• Actual Study Start Date: July 2015
• Actual Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 27, 2015)

Time to resolution of VOC [ Time Frame: 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

Original Primary Outcome Measures (submitted: August 2, 2015)

Readiness for discharge [ Time Frame: From hospitalisation until discharge, i.e. readiness for discharge calculated time from randomisation until day 7 ]

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

Current Secondary Outcome Measures (submitted: February 22, 2019)

• Frequency and pattern of treatment-emergent adverse event (TEAEs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From baseline (visit 1) until day 3-7 ]
  VAS (visual analog scale) every fourth hour. Range from 0 (no pain) to 100 (max pain)
• Duration of severest pain, [ Time Frame: From baseline (visit 1) until day 3-7 ]
  Defined as time to a 30% reduction in pain intensity (VAS)
• Cumulative dose of parenteral opioids [ Time Frame: From baseline (visit 1) until day 3-7 ]
  Total dose of parenteral opioids

Original Secondary Outcome Measures (submitted: August 2, 2015)

• Frequency and pattern of treatment-emergent adverse event (TEAEs) [ Time Frame: Time from start randomsiation until end of study, approximatly 1 month 1 week after randomisation ]
  All events to be reported from randomization until end of study
• Pharmacokinetic (PK) characteristics of sevuparin [ Time Frame: 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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).
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Sickle-Cell Disease

Intervention

• Drug: Sevuparin
  The Drug Product sevuparin solution for IV infusion
• Other: Placebo
  Placebo for IV infusion

Study Arms

• Placebo Comparator: Placebo
  Placebo infusion
  Intervention: Other: Placebo
• Experimental: Sevuparin
  Sevuparin infusion
  Intervention: Drug: Sevuparin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 15, 2019): 147
• Original Estimated Enrollment (submitted: August 2, 2015): 77
• Actual Study Completion Date: May 2019
• Actual Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 50 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bahrain, Jamaica, Lebanon, Netherlands, Oman, Saudi Arabia, Turkey

Administrative Information

• NCT Number: NCT02515838
• Other Study ID Numbers: TVOC01
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Modus Therapeutics AB
• Study Sponsor: Modus Therapeutics AB
• Collaborators: Ergomed

Investigators

• Principal Investigator: Dr Bart J Biemond, MD, PhD; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

• PRS Account: Modus Therapeutics AB
• Verification Date: February 2019