A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-42160443 in Subjects With Postherpetic Neuralgia and Post-Traumatic Neuralgia, Followed by a Double Blind Safety Extension and an Open-Label Safety Extension

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2008-007478-39-BE
• Date of registration: 26/06/2009
• Prospective Registration: Yes
• Primary sponsor: Janssen Cilag International, NV
• Public title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-42160443 in Subjects With Postherpetic Neuralgia and Post-Traumatic Neuralgia, Followed by a Double Blind Safety Extension and an Open-Label Safety Extension
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-42160443 in Subjects With Postherpetic Neuralgia and Post-Traumatic Neuralgia, Followed by a Double Blind Safety Extension and an Open-Label Safety Extension
• Date of first enrolment: 07/10/2009
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-007478-39
• 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: yes Other trial design description: open label in safety extension If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Netherlands, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
• Man or woman between 18 and 80 years of age, inclusive
• Subjects who have chronic neuropathic pain (pain persistent for greater than 6 months) that is moderate to severe in the opinion of the investigators) and are currently taking neuropathic 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 neuropathic 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 class, 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 the number and/or 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 their 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 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). Sponsor approval is required for the use of any other SNRI antidepressant for the treatment of neuropathic pain not listed here.

Note: Medications for treatment of neuropathic pain are limited to the guidelines provided above (refer to Maximal Neuropathic Pain Medication Allowed). No other classes of neuropathic pain medications (e.g., topical lidocaine, capsaicin, botulinum toxin) are permitted.

• 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 le
Exclusion criteria:
• 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 that does not have a stable pattern of symptoms for at least 6 months prior to Screening, 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
• History of ocular herpes simplex, HSV pneumonia, or HSV encephalitis
• Primary HSV infection or prophylactic therapy for HSV within the past 2 years
• Recurrent HSV reactivation during the past 2 years consisting of =4 episodes/year or requiring antiviral treatment
• Currently receiving chronic systemic immunosuppressive therapy
• 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 30 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.
• Women who are pregnant or breast-feeding
• 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

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

Health Condition(s) or Problem(s) studied

Postherpetic Neuralgia and Post-Traumatic Neuralgia
MedDRA version: 9.1 Level: LLT Classification code 10029223 Term: Neuralgia
MedDRA version: 9.1 Level: LLT Classification code 10036376 Term: Post herpetic neuralgia
MedDRA version: 9.1 Level: LLT Classification code 10054095 Term: Neuropathic pain

Intervention(s)

Product Name: JNJ42160443
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)

Main Objective: • 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
• 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 for up to 2 years

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).

Secondary Objective: • To evaluate the analgesic efficacy of JNJ-42160443 (10 mg; administered as a single, subcutaneous injection every 28 days) in reducing average pain intensity in subjects with posttraumatic neuralgia
• To evaluate the safety and tolerability of multiple doses of JNJ-42160443 (10 mg) when administered as a single, subcutaneous injection every 28 days to subjects with posttraumatic neuralgia for up to 2 years
• 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

Secondary ID(s)

42160443NPP2001