E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postherpetic Neuralgia and Post-Traumatic Neuralgia |
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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 | 10029223 |
E.1.2 | Term | Neuralgia |
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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 | 10036376 |
E.1.2 | Term | Post herpetic neuralgia |
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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 | 10054095 |
E.1.2 | Term | Neuropathic 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 |
•To evaluate the analgesic efficacy of JNJ-42160443 (1, 3, and 10 mg; administered as a single, subcutaneous injection every 28 days) in reducing average pain intensity, in subjects with postherpetic neuralgia and post-traumatic neuralgia •To evaluate the safety and tolerability of multiple doses of JNJ-42160443 (1, 3, and 10 mg), when administered as a single, subcutaneous injection every 28 days to subjects with postherpetic neuralgia and post-traumatic neuralgia for up to 2 years |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of JNJ-42160443 with respect to alternative pain endpoints (e.g. evening assessment of pain at its worst in the last 24 hours, neuropathic pain symptoms, pain severity, and pain-related interference with activities, Patient Global Impression of Change) •To evaluate the pharmacokinetics of JNJ-42160443 following multiple dose administrations •To evaluate the immunogenicity (antibodies to JNJ-42160443) associated with JNJ 42160443 treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subjects who have chronic neuropathic pain (pain persistent for greater than 6 months) that is moderate to severe in the opinion of the investigator and are currently taking pain medication but are not adequately controlled by standard of care (which may include antidepressants, antiepileptics, topical lidocaine, or opiods), or are not currently taking pain medications because they are intolerable to, or not willing to use, standard of care.
- Subjects currently taking medications for the treatment of neuropathic pain at Screening have 3 options: *They may continue taking their current pain medication: Subjects are required to be on a stable dose for at least 4 weeks prior to the first dose of study drug and must remain on this dose for the duration of the double-blind efficacy phase. The number and doses of medications for the treatment of neuropathic pain are limited to the guidelines provided below (refer to Maximal Neuropathic Pain Medication Allowed). If the number and/or doses of such medications must be reduced to fall within the acceptable limits for this study, then doses must be reduced (see next bullet). *They may reduce the number and/or dose of their current pain medications: If the number and/or dose exceed the limits of allowed neuropathic pain medications (refer to Maximal Neuropathic Pain Medication Allowed), then the number and/or dose must be reduced to fall within acceptable limits. This must be achieved at least 3 days or 5-half lives of the pain medication taken (whichever is longer) prior to the beginning of the Interactive Voice Response System (IVRS) baseline period. Medications with the potential to cause withdrawal symptoms should be tapered using a taper schedule that is determined by the investigator. Subjects must remain on this lowered number/dose of pain medication dose for the duration of the double-blind efficacy phase. *They may discontinue their current pain medication: If they choose to discontinue neuropathic pain medications, then a washout interval of 3 days or 5 half-lives of the pain medication taken, whichever is longer, prior to beginning the IVRS baseline period is required. Medications with the potential to cause withdrawal symptoms should be tapered using a taper schedule that is determined by the investigator. Maximal Neuropathic Pain Medication Allowed: Use of two or less of the following medications, each one from a different class, is permitted: + Anticonvulsants: gabapentin (≤ 1800 mg/day) or pregabalin (≤ 300 mg/day) + Opioid analgesics (≤ 60 mg/day oxycodone equivalent) or tramadol (≤ 200 mg/day) + Antidepressants: tricyclic antidepressants (≤ 75 mg/day amitriptyline equivalent), duloxetine (≤ 60 mg/day), or venlafaxine (≤ 150 mg/day)
- Subjects must have a mean average pain intensity score of at least 5, but less than 10, over 7 consecutive days on an 11-point numerical rating scale during the IVRS baseline period. Subjects are not permitted to have a pain score of less than 3 on 2 or more days within the 7 consecutive days. During the 7 consecutive days, at least 5 days of scores are required.
- Subjects with PHN: *Diagnosis of PHN includes a clear history of herpetic (varicella-zoster) rash and persistent pain in a dermatomal distribution area *Pain must be present for greater than 6 months after the onset of the dermatomal rash |
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E.4 | Principal exclusion criteria |
- Women who are pregnant or breast-feeding
- History of a separate pain condition (e.g., joint osteoarthritis) that is more severe than their pain due to their diagnosis of PHN or post-traumatic neuralgia, or, if in the opinion of the Investigator, the chronic pain condition could confound the subject’s assessment of neuropathic pain under this study
- Subjects with post-traumatic neuralgia that are characteristic of complex regional pain syndrome Type I, including: pain out of proportion to the severity of the injury, pain outside the distribution of nerve injury, changes in the skin color and/or temperature in the affected limb or body part, edema or excessive sweating of the affected limb or body part. Note, subjects with Type II CRPS are allowed in the study.
- Subjects with lumbar-sacral radiculopathy, failed low-back surgery, or spinal cord injury.
- Subject whose nerve injury or pain is expected to recover in the next 4 months
- Subjects with evidence of another neuropathic pain not under study, such as pain resulting from diabetic painful neuropathy, sensory neuropathies or pain caused by radiation, chemotherapy, alcohol, HIV infection
- Other peripheral neuropathy, paresthesia, or dysesthesia, or any other previously diagnosed neurologic condition causing the above noted symptoms that is not related with the PHN or posttraumatic neuralgia under the study
- Participation in an analgesia trial within 90 days of the first planned dose of study drug.
- Major surgeries (general or regional anesthesia), trauma, and nonhealing wounds/ulcers within 3 months prior to study drug
- History (within 1 year) of seizure, intrathecal therapy and ventricular shunts, radiotherapy to the cerebral area, mild or moderate traumatic brain injury, transient ischemic attack, or stroke, or meningitis
- History of severe traumatic brain injury within the past 15 years (consisting of 1 or more of the following: brain contusion, intracranial hematoma, either unconsciousness or post-traumatic amnesia lasting more than 24 hours) or with residual sequelae suggesting ongoing transient changes in consciousness
- History of epilepsy or multiple sclerosis
- In the investigator’s opinion, in consultation with the medical neurologist, any other conditions that could compromise the blood-brain barrier
- History of a malignancy (within the past 5 years) or current malignancy with the exception of basal cell carcinoma that has been treated and is no longer present
- Received an investigational drug (including vaccines) or used an investigational medical device within 30 days before the planned start of treatment (or 5 half-lives of the investigational drug, whichever is longer) or are currently enrolled in an investigational study.
- Significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric (e.g., schizophrenia, bipolar disorder, dementia), immunological (e.g., immune deficiency), or metabolic disturbances
- Type I or Type II diabetes, based on medical history or laboratory results consistent with diabetes mellitus (i.e. 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
- Active, major depression or generalized anxiety disorder, recent episode of either disorder within the past 3 months, and subjects with a BDI II score ≥ 29.
- History of suicide attempts or suicidal ideation in the past year
- Clinical diagnosis of human immunodeficiency virus (HIV) infection or clinical diagnosis of acquired immunodeficiency syndrome (AIDS) or any immune deficiency
- Known allergies, hypersensitivity, or intolerance to JNJ-42160443 or its excipients, including mammalian cell-derived (ie., Chinese hamster ovary) products
- Use of disallowed therapies: *As needed use of analgesics (e.g., non-steroidal anti-inflammatory drugs, cyclooxygenase-II inhibitors, topical capsaicin, topical lidocaine, and short acting opioids) must be discontinued at least 5 half-lives (of the analgesic medication) prior to the start of the IVRS baseline period and are prohibited during the double-blind efficacy phase. *Corticosteroids, other than topical and inhalation steroids, should not be taken during the trial or within the following periods prior to the start of the IVRS baseline period: Within 4 weeks (oral); within 8 weeks (intramuscular or soft tissue administration); within 3 months (intra articular administration); within 6 months (injection of depot steroids)
- Prior treatment with other experimental NGF-inhibitor therapy |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy evaluation is the daily evening assessment of average pain intensity over the last 24 hours using an 11-point numerical rating scale (NRS), where 0 = no pain and 10 = pain as bad as you can imagine.
The primary efficacy endpoint is the mean of the daily evening assessment of average pain intensity over the last 24 hours for the last 7 days of the double-blind efficacy phase minus the mean from the 7-day baseline period (7 days prior to the first dose of study drug).
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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 | Yes |
E.8.1.7.1 | Other trial design description |
open label in safety extension |
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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 | 20 |
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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End of trial is the last visit of the last subject undergoing the trial. |
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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 | 7 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 7 |