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

Sickle Cell Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01794000
• Other study ID #: 13038
• Secondary ID: H7T-MC-TADO2012-
• Status: Terminated
• Phase: Phase 3
• Start date: April 2013
• Est. completion date: December 2015

Study information

• Verified date: September 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 341
• Est. completion date: December 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• Prasugrel
Administered orally
• Placebo
Administered orally

Locations

Country	Name	City	State
Belgium	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
Belgium	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.	Montegnee
Brazil	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.	Rio De Janeiro
Canada	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.	Montreal	Quebec
Egypt	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.	Alexandria
Egypt	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.	Cairo
Egypt	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.	Fayoum
Egypt	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.	Ismailia
Egypt	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.	Mansoura
Egypt	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.	Zagazig
Ghana	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.	Agogo
Ghana	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.	Korle Bu
Italy	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.	Genova
Italy	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.	Modena
Italy	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.	Monza
Italy	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.	Padova
Italy	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.	Verona
Kenya	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.	Busia
Kenya	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.	Kisumu
Kenya	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.	Kombewa
Kenya	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.	Nairobi
Lebanon	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.	Beirut
Oman	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.	Muscat
Saudi Arabia	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.	Jeddah
Turkey	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.	Balcali Adana
Turkey	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.	Mersin
United Arab Emirates	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.	Abu Dhabi
United Kingdom	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.	London
United Kingdom	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.	Manchester
United Kingdom	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.	Tooting	London
United States	Emory University	Atlanta	Georgia
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Albert Einstein College of Medicine	Bronx	New York
United States	University of NC at Chapel Hill School of Medicine	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Ann & Robert H Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Childrens Hospital Medical Center	Cincinnati	Ohio
United States	Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Childrens Hospital of Michigan	Detroit	Michigan
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	St Jude Childrens Research Hospital	Memphis	Tennessee
United States	Children's Hospital of Oakland	Oakland	California
United States	Stanford Univ Medical Center	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St Christophers Hospital For Children	Philadelphia	Pennsylvania
United States	Childrens Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	Howard University Hospital	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Daiichi Sankyo, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Canada,  Egypt,  Ghana,  Italy,  Kenya,  Lebanon,  Oman,  Saudi Arabia,  Turkey,  United Arab Emirates,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Vaso-Occlusive Crisis (VOC) Events Per Participant Per Year (Rate of VOC)	The VOC is a composite endpoint of painful crisis or acute chest syndrome. Events that occurred within 7 days from the prior event onset date were not counted as a new episode. Data collected through the primary completion date reported below.	Randomization through 24 Months
Secondary	Monthly Rate of Days With Pain	Monthly rate of days with pain was measured through participant diaries using a modified version of the Faces Pain Scale-Revised (FPS-R). Each day participants selected the face on the scale that reflected their worst pain related to sickle cell disease (SCD) on that day. This pain scale contains six faces corresponding to the pain intensity of 0, 2, 4, 6, 8 or 10, in which 0 denotes no pain and 10 denotes the worst pain possible. Any day the participant selected a face other than face 0 was considered a day with pain. Monthly rate of days with pain was calculated for each participant by summing the number of days reported with any pain divided by the number of non-missing diary entries completed in the month. A month was defined as 4 weeks (28 days).The monthly rate was set to missing if there were more than 14 missing entries for the FPS-R in a specific month. Data collected through the primary completion date are present below.	Randomization through 9 Months
Secondary	Monthly Mean in Faces Pain Scale-Revised Score	Each day participants selected the face on the FPS-R scale that reflected their worst pain related to sickle cell disease (SCD) on that day. Monthly mean in FPS-R score was calculated for each participant by summing the FPS-R score divided by the number of non-missing diary entries completed in the month. This pain scale contains six faces corresponding to the pain intensity of 0, 2, 4, 6, 8 or 10, in which 0 denotes no pain and 10 denotes the worst pain possible. A month was defined as 4 weeks (28 days). The monthly mean in FPS-R score was set to missing if there were more than 14 missing entries for the FPS-R in a specific month. Data collected through the primary completion date are presented below.	Randomization through 9 Months
Secondary	Number of Painful Crisis Events Per Participant Per Year (Rate of Painful Crisis)	A painful crisis is defined as an onset of moderate to severe pain that lasts at least 2 hours for which there is no explanation other than vaso-occlusion and which requires therapy with oral or parenteral opioids, ketorolac, or other analgesics prescribed by a health care provider (HCP) in a medical setting such as a hospital, clinic, emergency room visit, or telephone management. The painful crisis that occurred within 7 days from the prior event onset date was not counted as a new episode. Data collected through the primary completion date are presented below.	Randomization through 24 Months
Secondary	Number of Hospitalizations for VOC Per Participant Per Year (Rate of Hospitalizations)	Hospitalization that occurred within 7 days of the prior event onset date were not counted as a new episode. Data collected through the primary completion date are presented below.	Randomization through 24 Months
Secondary	Number of Acute Chest Syndrome Per Participant Per Year (Rate of Acute Chest Syndrome)	Acute chest syndrome was defined as an acute illness characterized by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on a chest X-ray. Acute chest syndrome that occurred within 7 days of the prior event onset date was not counted as a new episode. Data collected through the primary completion date are presented below.	Randomization through 24 Months
Secondary	Number of Red Blood Cell (RBC) Transfusions Due to Sickle Cell Disease (SCD) Per Participant Per Year (Rate of RBC Transfusions)	RBC transfusions that occurred within 7 days of the prior event onset date were not counted as a new episode. Data collected through the primary completion date are presented below.	Randomization through 24 Months
Secondary	Monthly Rate of Days of Analgesic Use	Monthly rate of days of analgesic use was measured through participant diaries and was calculated for each participant by summing the number of days they reported analgesic use divided by the number of diary entries completed in the month. A month was defined as 4 weeks (28 days). The monthly rate was set to missing if there were more than 14 missing entries for analgesic use in a specific month. Data collected through the primary completion date are presented below.	Randomization through 9 Months
Secondary	Quarterly Rate of School Absence Due to Sickle Cell Pain	Quarterly rate of school absence due to sickle cell pain was measured through participant diaries and was calculated for each participant by summing the number of days with school absence due to sickle cell pain divided by the number of school dates in the quarter. A quarter was defined as 12 weeks. The quarterly rate was set to missing if there were more than 6 weeks of missing diary entries during a specific quarter. Data collected through the primary completion date are presented below.	Randomization through 9 Months
Secondary	Time to First Transient Ischemic Attack (TIA)/Ischemic Stroke		Randomization through 24 Months
Secondary	Number of Days Hospitalized for VOC	The total length of hospitalization in days for VOC was calculated for each participant. Data collected through the primary completion date are presented below.	Randomization through 24 Months
Secondary	Time From Randomization to First and Second VOC	Data collected through the primary completion date are presented below.	Randomization to First VOC and Second VOC respectively (up to 24 Months)
Secondary	Percentage of Participants With Hemorrhagic Events Requiring Medical Intervention	Medical intervention was defined as any medical evaluation resulting in therapy or further investigation, as determined by a trained medical professional. Data collected from the first dose of study medication through 10 days after last dose of study medication during the double blind study period are presented below.	First Dose through 24 Months

External Links

•   A Multinational Trial of Prasugrel for Sickle Cell Vaso-Occlusive Events