A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Dose-Loading Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-42160443 as Adjunctive Therapy in Subjects With Inadequately Controlled, Moderate to Severe, Chronic Low Back Pain

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-009857-17-BE
• Date of registration: 19/08/2009
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Dose-Loading Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-42160443 as Adjunctive Therapy in Subjects With Inadequately Controlled, Moderate to Severe, Chronic Low Back Pain
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Dose-Loading Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-42160443 as Adjunctive Therapy in Subjects With Inadequately Controlled, Moderate to Severe, Chronic Low Back Pain
• Date of first enrolment: 01/10/2009
• Target sample size: 360
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-009857-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
· Potential subjects must satisfy all of the following criteria to be enrolled in the study:
· Man or woman, 18 to 80 years of age, inclusive
· Documented clinical diagnosis of moderate to severe, chronic, LBP that must have been present (by history) for at least:
– =20 days/month
– =3 hours/day
– =6 months
· Have LBP classified by the Quebec Task Force Classification for Spinal Disorders as
– Category 1: pain without radiation to the extremity or
– Category 2: pain with radiation proximally to the knee and without neurologic signs
· Have an average pain intensity score of =5 averaged over the last 3 days of pain scores before randomization (Day 1) using an 11-point NRS, where the minimum single assessment score is =2. Subjects must have a minimum of 5 out of 6 possible assessments (twice daily assessments for the last 3 days of pain scores).
· Must be receiving at least 1 of the following analgesic regimens:
– Stable dose of NSAIDs for a minimum of 5 days each week for the 4 weeks before screening
– Stable dose of immediate-release opioids for a minimum of 5 days each week for the 4 weeks before screening, but not exceeding 200 mg oral morphine equivalents per day
– Stable dose of long-acting opioids for the 4 weeks before screening, but not exceeding 200 mg oral morphine equivalents per day; subjects receiving long acting opioids who use immediate-release opioids for breakthrough pain must not exceed, on average, more than 2 doses of immediate-release opioids per day during any 7 day period
· Have a MMSE score of =26 at screening
· Subjects who are sexually active must consent to utilize and document a medically acceptable and highly effective (<1% per year failure rate) method of contraception throughout the entire study from screening through 6 months after the last dose of study drug
– Medically acceptable, highly effective methods of contraception that may be used by the subject and/or partner include hormonal oral, transdermal, progestin implant, or injectable contraception, or intrauterine device (IUD), tubectomy or vasectomy
– For all women of childbearing potential, contraception must be consistently used for at least 3 months before the first dose of study drug through 6 months after the last dose of study drug. The screening phase may be extended up to 3 months to meet this requirement, but baseline safety evaluations must be performed within 3 weeks before the first dose of study drug.
– Subject or partner may also be postmenopausal (states having not experienced a menstrual period for a minimum of 12 months) or surgically sterile
– Further, subjects must agree to not donate sperm or eggs or attempt conception (pregnancy) from screening through 6 months after the last dose of study drug
· Women of childbearing potential must have a negative serum b human chorionic gonadotropin (b hCG) pregnancy test at screening and a negative urine b hCG pregnancy test at randomization (Day 1)
· Medically stable on the basis of physical examination, medical history, vital signs, clinical laboratory tests, and 12-lead ECG performed at screening
· Willing/able to comply with study procedures and evaluations specified in the protocol, including the completion of all PRO scales and questionnaires
· Willing/able to adhere to the prohibitions and restrictions specified in this protocol
· Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing
Exclusion criteria:
Potential subjects who meet any of the following criteria will be excluded from participating in the study:
• Have LBP classified by the Quebec Task Force Classification for Spinal Disorders as
– Category 3: pain with radiation distally beyond the knee and without neurologic signs or
– Category 4: Pain with radiation to the extremity and with neurologic signs (eg, focal muscular weakness, asymmetry of reflexes, sensory loss in a dermatome)
• History within the past year of any of the following:
– Seizure disorder
– Intrathecal therapy, epidural therapy, and ventricular shunts
– Mild or moderate traumatic brain injury
– Stroke
– Transient ischemic attack
– Meningitis
• History of brain injury within the past 15 years consisting of =1 of the following, or with residual sequalae suggesting transient changes in consciousness:
– Brain contusion
– Intracranial hematoma
– Either unconsciousness or posttraumatic amnesia lasting more than 24 hours
• History of epilepsy or multiple sclerosis
• Current diagnosis of fibromyalgia, complex regional pain syndrome (including reflex sympathetic dystrophy or causalgia), acute spinal cord compression, bowel or bladder dysfunction as a result of cauda equine compression, back pain caused by secondary infection, or pain caused by confirmed or suspected neoplasm
• Any new or unresolved neurologic deficits, including progressive deficits, within 6 months before screening. Transient neurologic deficits that are resolved within this period can be allowed if approved by the investigator.
• Active peripheral neuropathy, paresthesia, or dysesthesia, or any other previously diagnosed neurologic condition causing the above noted symptoms, except those related to their lumbosacral radiculopathy
• History of ocular herpes simplex, HSV pneumonia, or HSV encephalitis
• History of primary HSV infection and/or recurrent reactivation within the past 2 years or prophylactic therapy for HSV within the past 2 years
• Currently receiving chronic systemic immunosuppressive therapy
• Have undergone a surgical procedure for LBP within 6 months before the screening visit or planned surgery for LBP during the 12-week double-blind efficacy phase
• History of a major surgical procedure (ie, involving general or regional anesthesia), significant trauma, or a nonhealing wound or ulcer within 3 months before the screening visit
• Have had nerve or plexus block, including epidural steroid injections or facet blocks, within the 4 weeks before the screening visit
• History of diabetes mellitus or laboratory results consistent with diabetes mellitus (ie, fasting glucose =126 mg/dL or =7 mmol/L)
• Alanine aminotransaminase (ALT) or aspartate aminotransaminase (AST) =2.5 times the upper limit of normal (ULN)
• Serum creatinine of =1.8 mg/dL
• Have a Body Mass Index (BMI) of >39 kg/m2
• History of drug or alcohol abuse within the past 5 years
• History of or suspected human immunodeficiency virus (HIV) infection (Note: HIV testing is not required for this study)
• Severe depression as defined by a score of =29 on the BDI-II at screening
• Any other chronic pain condition that, in the investigator’s opinion, would interfere with the assessment of chronic LBP (eg, OA, rheumatoid arthritis, postherpetic neuralgia)
• History of malignancy within the past 2 years, with the exception of basal cell carcinoma that has been successfully treated
• Uncontrolled cardiovascular disease or hypertension (repeated systolic blood pressure (SBP) >160 mmHg or d

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderate to severe, chronic, low back pain (LBP) that is not adequately controlled by standard pain therapy
MedDRA version: 9.1 Level: LLT Classification code 10024891 Term: Low back pain

Intervention(s)

Product Code: JNJ42160443
Pharmaceutical Form: Solution for injection
Current Sponsor code: JNJ42160443
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint is the change from baseline to the end of the 12-week double-blind efficacy phase in the average LBP-related pain intensity score.
Key secondary efficacy evaluations are:
· ODI subscales and total score
· BPI Short Form pain severity and pain interference subscales
· PGA
Exploratory evaluations are:
· Rescue medication use
· Average pain intensity in the last 24 hours for up to 2 significant sources of pain not related to LBP
· Daily sleep interference assessments
· MOS Sleep Scale subscales
· SF-36 Health Survey subscales
· Work Productivity Questionnaire
· Subject experience using the STEP interview

Main Objective: The primary objectives of this study are to evaluate the analgesic effect size over 12 weeks of several doses and dosage regimens of JNJ-42160443 compared with placebo in subjects with moderate to severe, chronic, low back pain (LBP) that is not adequately controlled by standard pain therapy, and to evaluate the safety and tolerability of multiple SC doses of JNJ-42160443 in this population.

Secondary Objective: The key secondary objectives of this study are:
·Evaluate the efficacy of JNJ-42160443 compared with placebo as measured by back pain disability with subscales and total scores of the Oswestry Disability Index (ODI)
·Evaluate the efficacy of JNJ-42160443 compared with placebo as measured by the pain severity and pain interference subscales and total scores from the Brief Pain Inventory (BPI) Short Form
·Evaluate the efficacy of JNJ-42160443 compared with placebo as measured by the Patient Global Assessment (PGA)
·Evaluate the pharmacokinetics of JNJ-42160043 after multiple dose administrations of JNJ 42160443. A population PK approach will be used to characterize the disposition characteristics of JNJ 42160443 in this study.
·Evaluate the immunogenicity (antibodies to JNJ-42160443) associated with JNJ 42160443 treatment
·Evaluate the long-term efficacy, safety, and tolerability of JNJ-42160443 in this subject population during the 92-week double-blind extension phase

Secondary ID(s)

2009-009857-17-NL

42160443PAI2003