A Study to Assess the Effect of Ticagrelor in Reducing the Number of Days With Pain in Patients With Sickle Cell Disease (Hestia2)

• ClinicalTrials.gov Identifier: NCT02482298
• Recruitment Status: Completed
• First Posted: June 26, 2015
• Results First Posted: December 14, 2017
• Last Update Posted: December 19, 2018
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: June 17, 2015
• First Posted Date: June 26, 2015
• Results First Submitted Date: September 21, 2017
• Results First Posted Date: December 14, 2017
• Last Update Posted Date: December 19, 2018
• Actual Study Start Date: July 9, 2015
• Actual Primary Completion Date: November 16, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 14, 2017)

Change in Proportion of Days With Pain Due to Sickle Cell Disease as Measured by an eDiary [ Time Frame: Baseline through Week 12 ]

To investigate the efficacy of 2 different doses of ticagrelor versus placebo in reducing the number of days with pain due to sickle cell disease.

Original Primary Outcome Measures (submitted: June 23, 2015)

Number of days with pain due to Sickle Cell Disease [ Time Frame: 16 weeks ]

Pain assessment will be captured daily from enrolment to end of treatment using an eDiary.

Current Secondary Outcome Measures (submitted: November 14, 2017)

• Average of the Daily Worst Pain Values Reported Via eDiary [ Time Frame: Baseline through Week 12 ]
  To determine the efficacy of 2 different doses of ticagrelor versus placebo in reducing the intensity of pain due to sickle cell disease. Intensity of pain was recorded on an 11-point scale where 0 represented no pain and 10 represented the worst pain imaginable.
• Change in Proportion of Days With Analgesic Use Measured by an eDiary [ Time Frame: Baseline through Week 12 ]
  To assess the efficacy of 2 different doses of ticagrelor versus placebo in reducing the use of analgesics by patients with sickle cell disease.

Original Secondary Outcome Measures (submitted: June 23, 2015)

• Intensity of pain due to Sickle Cell Disease [ Time Frame: 16 weeks ]
  Pain intensity will be captured daily from enrolment to end of treatment using an eDiary. The numerical rating scale (NRS) asks the patient to rate the intensity of his/her worst pain and average pain during the past 24 hours and pain right now, using an 11-point scale where 0 represents "no pain" and 10 represents "pain as bad as you can imagine".
• Days of analgesic use [ Time Frame: 16 weeks ]
  Analgesic use will be captured daily from enrolment to end of treatment using an eDiary.

Current Other Pre-specified Outcome Measures (submitted: November 14, 2017)

• Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Patients) [ Time Frame: Baseline through Week 12 ]
  To assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with SCD
• Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Events) [ Time Frame: Baseline through Week 12 ]
  To assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with SCD

Original Other Pre-specified Outcome Measures (submitted: June 23, 2015)

• A composite to assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with Sickle cell disease [ Time Frame: 16 weeks ]
  Number of major bleeding or clinically relevant non-major bleeding events AE/ Serious Adverse Events (SAEs), Laboratory Safety Samples
• Safety of 2 different doses of ticagrelor versus placebo in patients with Sickle cell disease by assessment of blood pressure [ Time Frame: 16 weeks ]
  Unit of Measure: mmHg
• Safety of 2 different doses of ticagrelor versus placebo in patients with Sickle cell disease by assessment of pulse rate [ Time Frame: 16 weeks ]
  Unit of Measure: beats per minute (bpm)

Descriptive Information

• Brief Title: A Study to Assess the Effect of Ticagrelor in Reducing the Number of Days With Pain in Patients With Sickle Cell Disease
• Official Title: A Randomised, Double-blind, Double-dummy, Parallel-group, Multicenter, Phase IIb Study to Evaluate the Effect of Ticagrelor Versus Placebo in Reducing the Number of Days With Pain in Young Adults With Sickle Cell Disease
• Brief Summary: The purpose of this study is to determine whether ticagrelor is effective in reducing the number of days of pain, intensity of pain, and reducing the use of analgesics due to sickle cell disease

Detailed Description

This is a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, study evaluating 2 doses of ticagrelor in 90 patients aged 18 to 30 years, with sickle cell disease (SCD). Patients will be randomised to double-blind double-dummy treatment period in a 1:1:1 ratio (30 to each treatment group) to receive ticagrelor 10 mg twice daily (bid), or ticagrelor 45 mg bid, or placebo bid to determine the frequency of days with pain using an electronic diary (eDiary) every day. Approximately 180 patients will be enrolled. Patient will be followed for safety assessment during and after 2 weeks of treatment completion.

During the 16 week treatment period, patients will complete a daily eDiary concerning daily pain intensity, pain location, use of analgesics and absence from school or work. At the end of the study patients will be asked to rate the change in their sickle cell pain compared to the start of treatment. Platelet aggregation will be measured and reported as P2Y12 reaction units (PRU) pre-dose and 2 hours post-dose at week 4 and week 5 after treatment start. Pharmacokinetic (PK) parameters will be measured at 2 hours post-dose at week 4, and pre-dose and at 2 hours post-dose at week 5. Biomarkers will be assessed pre-dose at week 4, week 5 and week 8. During the study, patients will be evaluated for adverse events (AEs) including bleeding and vaso-occlusive crisis (VOC).

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Prevention
• Condition: Sickle Cell Disease

Intervention

• Drug: Ticagrelor
  Two arms: 1) 10 mg ticagrelor + 45 mg ticagrelor placebo or 2) 45 mg ticagrelor + 10 mg ticagrelor placebo. Drugs taken orally, twice a day (morning and evening, at least 12 hours apart) from randomization until the end of treatment.
• Drug: Placebo
  10 mg ticagrelor placebo + 45 mg ticagrelor placebo. Drugs taken orally, twice a day (morning and evening at least 12 hours apart) from randomization until the end of treatment

Study Arms

• Experimental: Dose A
  Intervention: Drug: Ticagrelor
• Experimental: Dose B
  Intervention: Drug: Ticagrelor
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 14, 2017): 87
• Original Estimated Enrollment (submitted: June 23, 2015): 90
• Actual Study Completion Date: November 16, 2016
• Actual Primary Completion Date: November 16, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Confirmed medical history or diagnosis of homozygous sickle cell (HbSS) or sickle beta-zero-thalassaemia (HbS/β0) by HPLC
• If treated with hydroxyurea, the dose must have been stable for 3 months

Exclusion Criteria:

• History of transient ischaemic attack or clinically overt cerebrovascular accident
• Moderate or severe hepatic impairment
• Treatment with chronic red blood cell transfusion therapy
• Pre-dominate cause of pain is not sickle cell disease related
• Chronic treatment with anticoagulants or antiplatelet drugs.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 30 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Egypt, France, Italy, Kenya, Lebanon, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT02482298
• Other Study ID Numbers: D5136C00008
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Maria Ignacia -Berraondo, MD; Quintiles, Inc.

• PRS Account: AstraZeneca
• Verification Date: November 2018