Central Pain Study for ABX-1431

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03138421
• Date of registration: 01/05/2017
• Prospective Registration: Yes
• Primary sponsor: Abide Therapeutics
• Public title: Central Pain Study for ABX-1431
• Scientific title: A Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Safety and Efficacy of ABX-1431 in Patients With Central Pain
• Date of first enrolment: August 1, 2017
• Target sample size: 9
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03138421
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

United Kingdom

Contacts

• Name: Jacqueline Palace, FRCP DM
• Affiliation: Oxford University Hospitals NHS Trust

• Name: Anu Jacob, MD DM FRCP
• Affiliation: The Walton Centre

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Longitudinally Extensive Transverse Myelitis

Neuromyelitis Optica Spectrum Disorder

Transverse Myelitis

Multiple Sclerosis

Intervention(s)

Drug: ABX-1431 HCl

Drug: Placebo

Primary Outcome(s)

Change in mean pain score between ABX-1431 HCl and placebo based on the Pain NRS-11 ordinal numeric rating scale [Time Frame: placebo, treatment (14 days)]

Secondary Outcome(s)

Actigraphically estimated parameters of sleep (WASO, TST, sleep efficiency, average overnight activity counts) and general activity measured by percentage of sedentary time, and moderate to high intensity activity [Time Frame: placebo, treatment (14 days)]

2-AG hydrolysis in PBMC [Time Frame: placebo, treatment (14 days)]

Short Form Brief Pain Inventory (SF-BPI) Scores [Time Frame: placebo, treatment (14 days)]

Patient Global Impression of Change (PGIC) score [Time Frame: placebo, treatment (14 days)]

Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) [Time Frame: placebo, treatment (14 days)]

Sleep interference (NRS-11) A NRS-11 scale recording sleep interference due to transverse myelitis pain / central pain in the previous week (in which 0 = no interference and 10 = greatest possible interference) [Time Frame: placebo, treatment (14 days)]

Proportion of patients achieving and maintaining >30%, >50%, reduction in mean pain intensity score compared to baseline and cumulative proportion of responders' analysis [Time Frame: placebo, treatment (14 days)]

ABX-11431 and metabolite M55 plasma PK [Time Frame: placebo, treatment (14 days)]

Secondary ID(s)

ABX-1431_PN009

Source(s) of Monetary Support

Please refer to primary and secondary sponsors