E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe, chronic, low back pain (LBP) that is not adequately controlled by standard pain therapy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024891 |
E.1.2 | Term | Low back pain |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
The key secondary objectives of this study are: To 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) - as measured by the pain severity and pain interference subscales and total scores from the Brief Pain Inventory (BPI) Short Form - as measured by the Patient Global Assessment (PGA)
Other secondary objectives are: - To 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. - To evaluate the immunogenicity (antibodies to JNJ-42160443) associated with JNJ 42160443 treatment - To evaluate the long-term efficacy, safety, and tolerability of JNJ-42160443 in this subject population during the 92-week double-blind extension phase |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 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 women of childbearing potential, contraception must be consistently used for at least 3 months before the first 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 β-human chorionic gonadotropin (β-hCG) pregnancy test at screening and a negative urine β-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 to participate in the study
- To participate in the optional pharmacogenomic component of this study, subjects must have signed the informed consent form for pharmacogenomic research indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit). Refusal to give consent for this component does not exclude a subject from participation in the clinical study.
To enter the double-blind extension phase, subjects must meet the following criteria: -Must have completed the double-blind efficacy phase of the study -Women of childbearing potential must have a negative urine β-hCG pregnancy test at the end of the double-blind efficacy phase (Week 13)
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E.4 | Principal exclusion criteria |
- Have LBP classified by the Quebec Task Force Classification for Spinal Disorders (refer to Attachment 1) 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
- Active 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 or those related to their lumbosacral radiculopathy 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
- 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 plasma 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 ³29 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 diastolic blood pressure (DBP) >100 mmHg
- Prior treatment with experimental NGF inhibitor therapy
- Known allergies, hypersensitivity, or intolerance to JNJ-42160443 or its excipients or mammalian cell-derived (ie, Chinese hamster ovary) products (
- Received an investigational drug or used an investigational medical device within 30 days before the screening visit (or 5 half-lives of the investigational drug, whichever is longer) or are currently enrolled in an investigational study
- Pregnant or breast-feeding
- Pending litigation due to chronic pain or disability
- Any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
- Employees of the investigator or site, with direct involvement in the proposed study or other studies under the direction of that investigator or site, as well as family members of the employees or the investigator |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy evaluation is the average LBP-related pain intensity score at the end of the 12 week double-blind efficacy phase. The twice daily NRS LBP-related pain assessment will be collected using the e-diary and the question will be “Select the number that best describes your low back pain on average during the past 12 hours on a scale of 0 to 10, where 0=no pain and 10=pain as bad as you can imagine”. The baseline score is defined as the average LBP-related pain intensity scores averaged over the last 3 days of pain scores before random assignment. The end of the 12-week double-blind efficacy phase score is defined as the average LBP-related pain intensity scores averaged over the last 7 days of this phase.
The primary efficacy endpoint is the change from baseline to the end of the 12-week double-blind efficacy phase in the average pain intensity score.
Key secondary efficacy evaluations are: - Oswestry Disability Index (ODI) subscale and total scores - Brief Pain Inventory (BPI) Short - Patient Global Assessment (PGA) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study is considered completed with the last visit of the last subject participating in the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |