A Phase 3, Double-Blind, Randomized, Efficacy and Safety Comparison of Prasugrel and Placebo in Pediatric Patients With Sickle Cell Disease.

A Study of Prasugrel in Pediatric Participants With Sickle Cell Disease (SCD)

Lead Sponsor

Eli Lilly and Company

Collaborators

Daiichi Sankyo, Inc.

Source

Eli Lilly and Company

Oversight Info

Has Dmc

Yes

Brief Summary

The main purpose of the study is to evaluate the efficacy and safety of the study drug known as prasugrel for the reduction of Vaso-Occlusive Crisis events in pediatric participants with sickle cell disease. The study will also investigate reduction in daily pain in children who have sickle cell disease.

Detailed Description

The submission database was validated for data reported through the data cutoff date for the submission database lock (SDBL). The SDBL data cutoff was 17 July 2015 for all participants except for 2 in the youngest age group, for whom the SDBL data cutoff occurred on 08 August 2015. The data cutoff date for SDBL corresponds to the primary completion date for the study. The SDBL occurred on 31 August 2015. The study was stopped following SDBL and review of the topline information indicated that the primary and secondary efficacy endpoints were not met. Subsequently, the Sponsor requested that participants discontinue study drug immediately and that discontinuation visits for all active study participants be conducted as soon as feasible. After the data cutoff date for SDBL, the Sponsor continued to collect safety data through the final participants contact; some additional efficacy data were collected through the final visit. The last patient visit (LPV) occurred on 17 December 2015, which corresponds to the study completion date and led to the planned supplemental database lock (PSDBL) on 22 January 2016. This supplemental data base was originally designed to capture additional blinded and randomized information to enhance safety data for labeling should the study have been positive. The safety information contained in this record reflects the entire safety information and reflects the information from the supplemental data base lock in January of 2016. The efficacy information contained in this record reflects the information collected through primary completion date in the submission database. Primary analyses of the major efficacy objectives were repeated using the entire double-blind period data from the PSDBL and did not change the original conclusions and were consistent with the results from the original efficacy analyses included in the SDBL.

Overall Status

Terminated

Start Date

2013-04-01

Completion Date

2015-12-01

Primary Completion Date

2015-07-01

Phase

Phase 3

Study Type

Interventional

Primary Outcome

Measure	Time Frame
Number of Vaso-Occlusive Crisis (VOC) Events Per Participant Per Year (Rate of VOC)	Randomization through 24 Months

Secondary Outcome

Measure	Time Frame
Monthly Rate of Days With Pain	Randomization through 9 Months
Monthly Mean in Faces Pain Scale-Revised Score	Randomization through 9 Months
Number of Painful Crisis Events Per Participant Per Year (Rate of Painful Crisis)	Randomization through 24 Months
Number of Hospitalizations for VOC Per Participant Per Year (Rate of Hospitalizations)	Randomization through 24 Months
Number of Acute Chest Syndrome Per Participant Per Year (Rate of Acute Chest Syndrome)	Randomization through 24 Months
Number of Red Blood Cell (RBC) Transfusions Due to Sickle Cell Disease (SCD) Per Participant Per Year (Rate of RBC Transfusions)	Randomization through 24 Months
Monthly Rate of Days of Analgesic Use	Randomization through 9 Months
Quarterly Rate of School Absence Due to Sickle Cell Pain	Randomization through 9 Months
Time to First Transient Ischemic Attack (TIA)/Ischemic Stroke	Randomization through 24 Months
Number of Days Hospitalized for VOC	Randomization through 24 Months
Time From Randomization to First and Second VOC	Randomization to First VOC and Second VOC respectively (up to 24 Months)
Percentage of Participants With Hemorrhagic Events Requiring Medical Intervention	First Dose through 24 Months

Enrollment

341

Condition

Sickle Cell Disease

Intervention

Intervention Type

Drug

Intervention Name

Prasugrel

Description

Administered orally

Arm Group Label

Prasugrel

Other Name

LY640315

Effient

Efient

Intervention Type

Drug

Intervention Name

Placebo

Description

Administered orally

Arm Group Label

Placebo

Eligibility

Criteria

Inclusion Criteria: - Have SCD [homozygous sickle cell (HbSS) or hemoglobin (HbS) Beta^0 thalassemia] - Are participants with SCD who have had ≥2 episodes of vaso-occlusive crisis (VOC) in the past year - Have a body weight ≥19 kilograms (kg) and are ≥2 and <18 years of age, inclusive at the time of screening - If participants are ≥2 and ≤16 years of age, must have had a transcranial Doppler within the last year Exclusion Criteria: - History of: transient ischemic attack (TIA)/ ischemic or hemorrhagic stroke, severe head trauma, intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm - History of abnormal or conditional [velocity in middle or anterior cerebral, or internal carotid artery ≥170 centimeter per second (cm/sec)] transcranial Doppler within the last year - History of, or are undergoing treatment with, chronic red blood cell (RBC) transfusion therapy - Are at an increased risk for bleeding complications - Are receiving chronic treatment with nonsteroidal anti-inflammatory drug (NSAID)s and cannot be switched to another analgesic

Gender

All

Minimum Age

2 Years

Maximum Age

17 Years

Healthy Volunteers

Overall Official

Last Name	Role	Affiliation
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Study Director	Eli Lilly and Company

Location

Facility

Children's Hospital of Oakland
Oakland California 94609 United States

Stanford Univ Medical Center
Palo Alto California 94304 United States

Connecticut Children's Medical Center
Hartford Connecticut 06106 United States

Howard University Hospital
Washington District of Columbia 20060 United States

Emory University
Atlanta Georgia 30322 United States

Memorial Health University Medical Center
Savannah Georgia 31404 United States

Ann & Robert H Lurie Children's Hospital of Chicago
Chicago Illinois 60611 United States

Boston Children's Hospital
Boston Massachusetts 02115 United States

Childrens Hospital of Michigan
Detroit Michigan 48201 United States

Children's Mercy Hospital
Kansas City Missouri 64108 United States

Albert Einstein College of Medicine
Bronx New York 10467 United States

University of NC at Chapel Hill School of Medicine
Chapel Hill North Carolina 27599 United States

Childrens Hospital Medical Center
Cincinnati Ohio 45229 United States

Rainbow Babies and Children's Hospital
Cleveland Ohio 44106 United States

Children's Hospital of Philadelphia
Philadelphia Pennsylvania 19134 United States

St Christophers Hospital For Children
Philadelphia Pennsylvania 19134 United States

Childrens Hospital of Pittsburgh
Pittsburgh Pennsylvania 15224 United States

Medical University of South Carolina
Charleston South Carolina 29425 United States

St Jude Childrens Research Hospital
Memphis Tennessee 38105 United States

Mary Bridge Children's Hospital and Health Center
Tacoma Washington 98405 United States

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Brussel 1200 Belgium

Location Countries

Country

Belgium

Brazil

Canada

Egypt

Ghana

Italy

Kenya

Lebanon

Oman

Saudi Arabia

Turkey

United Arab Emirates

United Kingdom

United States

Verification Date

2016-06-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Sponsor

Has Expanded Access

Condition Browse

Anemia, Sickle Cell

Secondary Id

H7T-MC-TADO

2012-003837-41

Number Of Arms

Intervention Browse

Mesh Term

Prasugrel Hydrochloride

Arm Group

Arm Group Label

Prasugrel

Arm Group Type

Experimental

Description

Participants will be titrated from initial daily dose of 0.08 milligram per kilogram (mg/kg) of orally administered prasugrel monotherapy at randomization to a dose that will achieve a P2Y12 reaction units (PRU) level of 231 to 136, as measured by VerifyNow instrument. This corresponds to a range of platelet inhibition of approximately 30% to 60%. The maximum possible dose allowed is 0.12 mg/kg daily, not to exceed 10 mg daily.

Arm Group Label

Placebo

Arm Group Type

Placebo Comparator

Description

Participants in this treatment group will receive daily orally administered placebo and will follow visit schedule identical to that in the active treatment group.

Firstreceived Results Date

N/A

Why Stopped

The study is being terminated for lack of efficacy.

Removed Countries

Country

France

Netherlands

Patient Data

Sharing Ipd

Yes

Ipd Description

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com. This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.

Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary Purpose

Treatment

Masking

Triple (Participant, Care Provider, Investigator)

Study First Submitted

February 14, 2013

Study First Submitted Qc

February 14, 2013

Study First Posted

February 18, 2013

Last Update Submitted

June 15, 2016

Last Update Submitted Qc

June 15, 2016

Last Update Posted

July 27, 2016

Results First Submitted

June 15, 2016

Results First Submitted Qc

June 15, 2016

Results First Posted

July 27, 2016

ClinicalTrials.gov processed this data on August 29, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.

Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.

Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.

ICH GCP | Clinical Trials Registry