Study to Evaluate the Safety and Efficacy of Placulumab (CEP-37247) Administered by the Transforaminal Epidural Route for the Treatment of Patients With Lumbosacral Radicular Pain Associated With Disk Herniation

NCT01240876 | Completed Phase 1

• 1 other identifier: C37247/1083
• Study Type: interventional
• Target: 98
• Locations: 2 countries
• Sites: 24

Brief Summary

The primary objective of the study is to evaluate the safety and efficacy of CEP-37247 compared with placebo as assessed by the occurrence of adverse events, and the mean change in average pain intensity (API) in the affected leg.

Conditions

Sciatica

Keywords

Sciatica; Pain

Outcome Measures

Primary Outcomes (2)

• Occurrence of adverse events compared to placebo

  throughout the 28-week double-blind treatment period

• Mean change in the weekly average of daily average pain intensity (API) in the affected leg on the 11-Point Numerical Rating Scale (NRS-11)

  The average pain intensity over the past 24 hours on the NRS-11 will be collected daily by electronic diary.

  at week 4 compared with baseline

Secondary Outcomes (19)

• Weekly average of daily leg API score as assessed by the NRS-11 from electronic diary entries

  at each of the first 6 weeks

• Weekly average of daily back API score as assessed by the NRS-11 from electronic diary entries

  at each of the first 6 weeks

• Weekly average of daily worst leg pain score as assessed by the NRS-11 from electronic diary entries

  at each of the first 6 weeks

• Weekly average of daily worst back pain score as assessed by the NRS-11 from electronic diary entries

  at each of the first 6 weeks

• Patients with 30% and 50% reductions in average pain over the previous 24 hours as measured by the Brief Pain Inventory Short Form (BPI-SF)

  at 1, 2, 4, 6, 14, and 28 weeks

Study Arms (2)

CEP-37247

EXPERIMENTAL

Drug: CEP-37247

Matching placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

CEP-37247 DRUG

0.5-, 1-, 3-, 6-, and 12-mg doses of CEP-37247 will be administered by the transforaminal epidural route.

Also known as: placulumab

CEP-37247

Placebo DRUG

Matching placebo vials will be filled with the buffered solution for CEP-37247.

Matching placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Over the 4 days prior to the randomization visit, the patient has a mean score greater than or equal to 5 (of 10) for "Average Pain Over the Past 24 Hours" for the pain in the affected leg as assessed by the 11-Point Numerical Rating Scale (NRS-11) captured in the electronic diaries. The patient must have valid (non-missing) data for at least 3 out of the 4 days, and the mean score must be at least 5 without rounding.
• The patient has a current diagnosis of lumbosacral radicular pain. Pain must radiate into the leg in a dermatomal/myotomal distribution consistent with the diagnosis of lumbosacral radicular pain in the suspected involved nerve root. Based on history and medical records (if available), the duration of the current episode of pain must be between 6 and 52 weeks duration.
• Diagnosis must be confirmed by magnetic resonance imaging (MRI) (or existing computed tomography \[CT\] or MRI related to the symptoms present at screening) performed within 6 months prior to screening and demonstrating disk herniation at a location consistent with the clinical symptoms of radicular pain. Other incidental pathology is permitted as long as it is asymptomatic and believed not causal of the primary diagnosis of lumbosacral radicular pain at the specific spinal level as described below.
• The patient must have at least 1 of the following: a positive straight leg raise (L5-S1), positive femoral stretch test (L3-L4), or other positive test result upon physical examination that is consistent with the presence of nerve root irritation at the nerve root suspected to be involved in the diagnosed lumbosacral radicular pain at screening.
• Herniation must affect L3-L4, L4-L5, or L5-S1 and must be consistent with clinical presentation of the current episode of lumbosacral radicular pain as described above.
• Patients with significant or progressive sensory impairment or motor impairment (such as foot drop) must be assessed on a case-by-case basis by the investigator, and must in each case receive written approval of the Sponsor prior to randomization.
• There must be confirmation that the patient does not have an active tuberculosis infection at screening. The patient should have either a negative QuantiFERON®-TB Gold blood test or negative tuberculin skin test (TST) result at screening; however if QuantiFERON®-TB Gold test or TST is positive, a chest radiogram may be used to determine whether a patient has an active infection.
• The patient is willing to keep all analgesic medication and other therapy usage (such as physiotherapy, acupuncture, or transcutaneous electrical nerve stimulation \[TENS\]) stable or decreased during the study and use only the rescue pain medication as needed and as specified by the protocol.
• The patient is in good health (with the exception of the condition under study) as determined by a medical and psychiatric history, medical examination, ECG, serum chemistry, hematology, urinalysis, and serology.
• Women of childbearing potential (ie, not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study, and have a negative pregnancy test at screening.

You may not qualify if:

• The patient:
• has a documented history of an allergic reaction (hives, rash, etc.) or a clinically significant intolerance to study drug or ingredients.
• has a body mass index (BMI) greater than 40 kg/m2.
• the patient has an established history of a major psychiatric disorder, not controlled with medication or appears to have anxiety that would interfere with clinical pain scores or participation in the trial.
• has clinically significant abnormalities in clinical chemistry, hematology or urinalysis, including serum glutamic-oxaloacetic transaminase/aspartate aminotransferase (AST) or serum glutamic-pyruvic transaminase/alanine aminotransferase (ALT) greater than or equal to 3 times the upper limit of the reference range or an estimated glomerular filtration rate (eGFR) less than or equal to 30 mL/min/1.73 m2 (Modification of Diet in Renal Disease \[MDRD\] study formula) at screening.
• has received an intra-epidural steroid injection for the treatment of the current episode of sciatica during the last 3 months prior to screening.
• has significant pain unrelated to the disk herniation that would significantly compromise assessment of the radicular back and leg pain related to the disk herniation.
• has radiologic evidence of disk herniation at more than 1 spinal level, and clinical evidence of lumbosacral radicular pain at more than 1 spinal nerve corresponding to the levels of the multiple disk herniations.
• has received any investigational drug within 30 days prior to screening, or is scheduled to receive an investigational drug other than blinded study drug during the course of this study.
• has had lumbar or sacral back surgery related to the specific disk that is the cause of the radicular pain upon presentation to the study, or currently plans to undergo spine surgical intervention while in the study.
• has received epidural corticosteroid injections in the back within 3 months of screening.
• is involved in an ongoing worker's compensation claim, disability claim, or litigation related to any pain problem.
• has any active infection that is not self-limiting and not resolved prior to study drug administration.
• has a history of malignancy or evidence of malignancy or lymphoproliferative or neoplastic disease with the exception of successfully treated basal or squamous cell carcinoma of the skin or cervical intraepithelial neoplasia within 5 years of the screening visit.
• has a history of systemic fungal infection.

Sponsors & Collaborators

• Cephalon: lead

Study Sites (24)

Teva Investigational Site 22

La Mesa, California, United States

Location

Teva Investigational Site 18

Laguna Hills, California, United States

Location

Teva Investigational Site 19

Pasadena, California, United States

Location

Teva Investigational Site 2

Pasadena, California, United States

Location

Teva Investigational Site 14

Orlando, Florida, United States

Location

Teva Investigational Site 5

Sarasota, Florida, United States

Location

Teva Investigational Site 10

Marietta, Georgia, United States

Location

Teva Investigational Site 13

Marietta, Georgia, United States

Location

Teva Investigational Site 9

Bloomington, Illinois, United States

Location

Teva Investigational Site 15

Overland Park, Kansas, United States

Location

Teva Investigational Site 8

Shreveport, Louisiana, United States

Location

Teva Investigational Site 20

Winston-Salem, North Carolina, United States

Location

Teva Investigational Site 16

Dayton, Ohio, United States

Location

Teva Investigational Site 21

Eugene, Oregon, United States

Location

Teva Investigational Site 17

Altoona, Pennsylvania, United States

Location

Teva Investigational Site 1

Greenville, South Carolina, United States

Location

Teva Investigational Site 11

North Charleston, South Carolina, United States

Location

Teva Investigational Site 6

Spartanburg, South Carolina, United States

Location

Teva Investigational Site 4

Orem, Utah, United States

Location

Teva Investigational Site 3

Salt Lake City, Utah, United States

Location

Teva Investigational Site 103

Caulfied South, Australia

Location

Teva Investigational Site 102

Malvern East, Australia

Location

Teva Investigational Site 100

North Terrace, Australia

Location

Teva Investigational Site 101

St Leonards, Australia

Location

MeSH Terms

Conditions

Sciatica; Pain

Condition Hierarchy (Ancestors)

Sciatic Neuropathy; Mononeuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Neuralgia; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Sponsor's Medical Expert, Associate Director, Clinical Research, MD, PhD

  Cephalon

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2010
• First Posted: November 15, 2010
• Study Start: January 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: April 1, 2013
• Last Updated: July 21, 2016

Record last verified: 2016-07

Locations

US (20); AU (4)