Central Pain Study for ABX-1431

Brief Title

Central Pain Study for ABX-1431

Official Title

A Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Safety and Efficacy of ABX-1431 in Patients With Central Pain

Brief Summary

      This study will determine the safety and tolerability of ABX-1431 in patients with central
      pain when added on to background pain therapy.

      During the course of this study, each participant will take a daily dose of 20 mg of ABX-1431
      or a matching placebo for approximately 7 to 9 weeks.
    

Detailed Description

      This is a double-blind, placebo-controlled crossover study, randomized, crossover study of
      ABX-1431 HCl as add-on therapy in the treatment of central neuropathic pain.The efficacy of
      ABX-1431 will also be assessed by the change in pain intensity scores using a numerical
      rating scale (NRS-11).

      All patients will undergo a screening visit for enrollment criteria. Eligible patients will
      be treated with daily medication for 7 to 9 weeks, which will include some treatment with
      placebo and some treatment with ABX-1431 HCl. Patients will use a web based application to
      record their daily average pain using a numerical rating scale (NRS-11).

      This study will enroll up to 32 patients with chronic central pain due to one of the four
      following diagnostic groups: Neuromyeliltis Optica Spectrum Disorder (NMOSD), longitudinally
      extensive transverse myelitis (LETM), Multiple Sclerosis (MS), and Transverse Myelitis (TM).
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Change in mean pain score between ABX-1431 HCl and placebo based on the Pain NRS-11 ordinal numeric rating scale

Secondary Outcome

 Short Form Brief Pain Inventory (SF-BPI) Scores

Condition

Neuromyelitis Optica Spectrum Disorder

Intervention

ABX-1431 HCl

Study Arms / Comparison Groups

 ABX-1431 HCl
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

9

Start Date

August 1, 2017

Completion Date

July 24, 2018

Primary Completion Date

July 23, 2018

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with chronic central pain, present for at least 3 months due to one of the
             four following diagnostic groups: NMOSD, LETM, MS, or TM.

               -  Patient has a diagnosis of NMOSD with anti-AQP4 IgG or without AQP4-IgG as
                  defined by the International Panel for NMO Diagnosis at least 3 months prior to
                  the screening visit (IPND 2015)

               -  Patients with idiopathic, LETM, comprising an intramedullary MRI lesion or
                  continuous segments of spinal cord atrophy with a clinical history consistent
                  with acute myelitis, and with chronic pain syndrome consistent with the lesion
                  neuroanatomy may be enrolled. These LETM patients must also demonstrate evidence
                  of acute, inflammatory myelopathy in the past (e.g. clinically acute symptomatic
                  myelitis plus inflammatory CSF analysis (e.g. elevated WBC and IgG index) or
                  imaging consistent with inflammatory myelopathy). LETM must be diagnosed at least
                  3 months prior to the screening visit.

               -  Patient with MS defined by McDonald criteria [1] or Poser criteria [2] at least 3
                  months prior to screening visit.

               -  Patients with post-infectious, autoimmune or idiopathic TM diagnosed by a
                  neurologist at least 6 months prior to the screening visit.

          -  Patient's chronic pain must be neuropathic in nature, and anatomically plausible based
             on underlying neuropathology. If patient has an additional source of pain (e.g.,
             vascular ischemic pain, transient spasm associated pain, headache, chronic lower back
             pain or concomitant osteoarthritic joint pain), the central neuropathic pain must be
             clearly identifiable by the patient, as assessed by the Investigator.

          -  The Investigator determines that the patient can enter daily NRS-11 pain intensity
             data on an internet connected device such as a smart phone, tablet computer or desktop
             computer with reliable internet service. Patients that do not have a device will be
             supplied one for the duration of the study. At the direction of the patient, the
             patient's caregivers may enter the pain intensity data.

          -  At Visit 2, patient's pain is ≥ 4 on the NRS-11 pain intensity scale, on at least 4 of
             the 7 days preceding randomization.

          -  Patients taking immunosuppressive therapy (IST) for relapse prevention of NMOSD or TM
             or taking disease modifying therapy (DMT) for MS must be on a stable maintenance
             dose(s) of IST or DMT for 30 days prior to screening and must be expected to maintain
             the IST or DMT regimenduring this study.

          -  Patients taking oral corticosteroids must be on a stable dose of medication for at
             least one week before study start and must be expected to remain on a stable dose
             during this study. The dose may be no more than prednisolone 20 mg daily or
             equivalent.

          -  For patients taking antibody therapy for NMOSD relapse prevention (e.g. rituximab,
             eculizumab or tocilizumab), therapy must be discontinued at least 6 months prior to
             screening and patients must be willing to refrain from use during this study.

          -  Patients taking daily neuropathic or central pain medications (e.g. gabapentin,
             amitriptyline, lamotrigine) must be on a stable dose of medication for 30 days before
             study start and must be expected to remain on a stable dose during this study.

          -  Patients must give written informed consent.

          -  Patients must be willing and able to comply with the protocol requirements for the
             duration of the study.

          -  Female patients of child-bearing potential must have a negative pregnancy test [serum
             human chorionic gonadotropin (HCG)]. They must practice a highly effective, reliable
             and medically approved contraceptive regimen during the study (i.e. theoretical
             failure rate less than 1% per year including oral or parenteral hormonal
             contraception, Nuvaring, intrauterine device (IUD) or male condom plus spermicide).
             Post-menopausal women may enter this study. Post-menopausal women are defined as those
             without menses in the past 12 months, and with a serum follicle stimulating hormone
             (FSH) in the post-menopausal range. Women who are surgically sterile may enter this
             study with historical documentation of surgical procedure and a negative pregnancy
             test.

          -  Male patients must be willing to use a condom with sexual partners during this study
             until the poststudy visit. Male patients must be willing to abstain from sperm
             donation for 3 months after the completion of this study.

        Exclusion Criteria:

          -  Patients with chronic central pain due to trauma, vascular causes, active infection,
             neoplasm, radiation, metabolic, toxic or other non-inflammatory brain disease or
             myelopathy are excluded. Patients with trigeminal neuralgia, either as an isolated
             condition or with MS are excluded. Patients with a history of encephalitis are
             excluded. Patients with systemic inflammatory autoimmune disorders associated with TM
             are excluded (e.g. sarcoidosis, systemic lupus erythematosus, Sjogren's syndrome,
             Behcet's Syndrome, rheumatoid arthritis). TM secondary to infection of the nervous
             system is excluded (e.g. herpes virus, Lyme disease). TM associated with HIV infection
             is excluded.

          -  Patient has an onset of an MS, LETM or TM relapse or NMOSD acute episode within 60
             days before the study start.

          -  Patients with unresolved infections, AIDS myelopathy, or degenerative neurological
             conditions.

          -  Patient has received the following within 60 days before study start:

               -  Intrathecal baclofen.

               -  Injection therapies such a botulinum toxin, anesthetic or nerve block to control
                  pain.

               -  Plasma exchange

          -  Patients taking daily oral opioid drugs are excluded.

          -  Patient is taking carbamazepine or oxcarbazine or eslicarbazepine or other potent
             cytochrome P450 3A4/5 inducers [e.g. rifampin, St. John's Wort (Hypericum perforatum),
             phenytoin]. Patient is taking strong P450 3A4/5 inhibitors including atazanavir,
             bocepravir, clarithromycin, grapefruit juice, indinavir, itraconazole, ketoconazole,
             nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, or
             voriconazole.

          -  Patient has evidence of alcohol, drug or chemical abuse, at study start or within 1
             year before the study start.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Jacqueline Palace, FRCP DM, , 

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations


NCT ID

NCT03138421

Organization ID

ABX-1431_PN009


Responsible Party

Sponsor

Study Sponsor

Abide Therapeutics


Study Sponsor

Jacqueline Palace, FRCP DM, Principal Investigator, Oxford University Hospitals NHS Trust


Verification Date

January 2019