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

Lilly

Status and phase: Terminated; Phase 3

Conditions: Sickle Cell Disease

Treatments: Drug: Prasugrel; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01794000

2012-003837-41 (EudraCT Number)

H7T-MC-TADO (Other Identifier)

13038

Details and patient eligibility

About

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.

Full 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.

Enrollment: 341 patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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341 participants in 2 patient groups, including a placebo group

Prasugrel

Experimental group

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.

Treatment:

Drug: Prasugrel

Placebo

Placebo Comparator group

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.

Treatment:

Drug: Placebo