Neuromyelitis Optica Spectrum DisorderPhase 1NCT03138421
Central Pain Study for ABX-1431
A Phase 1 study testing ABX-1431 HCl in people with Neuromyelitis Optica Spectrum Disorder and Transverse Myelitis, run by Abide Therapeutics at 2 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuromyelitis Optica Spectrum Disorder, Transverse Myelitis, Multiple Sclerosis
- What is being tested?
- ABX-1431 HCl
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 1 Aug 2017to 24 Jul 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
The Walton Centre
Liverpool, L97LJ
Oxford University Hospitals NHS Foundation Trust
Oxford, OX3 9DU
About this study
Official title: A Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Safety and Efficacy of ABX-1431 in Patients With Central Pain
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.
Read the 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).
- Conditions
- Neuromyelitis Optica Spectrum Disorder, Transverse Myelitis, Multiple Sclerosis, Longitudinally Extensive Transverse Myelitis
- Being tested
- ABX-1431 HCl, Placebo
- Medical subject headings
- Neuromyelitis Optica, Myelitis, Transverse, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABX-1431 HClDrug
ABX-1431 HCl, capsules, 20 mg
PlaceboDrug
Matching placebo
| Study group | Role | What they receive |
|---|---|---|
| ABX-1431 HCl | Experimental | Not described Receives: Drug: ABX-1431 HCl |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mean pain score between ABX-1431 HCl and placebo based on the Pain NRS-11 ordinal numeric rating scale
The treatment difference of ABX-1431 HCl versus placebo is estimated from the change from baseline in daily NRS-11 Pain to the final 7 days of treatment in each two-week treatment period. Baseline levels of pain or taken from the final 7 days of treatment in the period preceding each double-blind treatment period.
Measured: placebo, treatment (14 days)
Secondary outcomes (8)
Short Form Brief Pain Inventory (SF-BPI) Scores
Difference in the change from baseline between ABX-1431 HCl and placebo
Measured: placebo, treatment (14 days)
Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2)
Difference in the change from baseline between ABX-1431 HCl and placebo
Measured: placebo, treatment (14 days)
Patient Global Impression of Change (PGIC) score
Difference in the change from baseline between ABX-1431 HCl and placebo
Measured: 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
Difference in the change from baseline between ABX-1431 HCl and placebo
Measured: placebo, treatment (14 days)
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
Difference in the change from baseline between ABX-1431 HCl and placebo
Measured: 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)
Difference in the change from baseline between ABX-1431 HCl and placebo
Measured: placebo, treatment (14 days)
ABX-11431 and metabolite M55 plasma PK
Difference in the change from baseline between ABX-1431 HCl and placebo
Measured: placebo, treatment (14 days)
2-AG hydrolysis in PBMC
Difference in the change from baseline between ABX-1431 HCl and placebo
Measured: placebo, treatment (14 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2017
- Study start1 Aug 2017
- Primary completion23 Jul 2018
- Study completion24 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuromyelitis Optica Spectrum DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abide Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jacqueline Palace, FRCP DM, Principal investigator, Oxford University Hospitals NHS TrustAnu Jacob, MD DM FRCP, Principal investigator, The Walton Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03138421
- Sponsor's protocol ID
- ABX-1431_PN009
- Status last verified
- Jan 2019
- First submitted
- 1 May 2017
- Last updated
- 25 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Safety and Efficacy of ABX-1431 in Patients With Central Pain
- ClinicalTrials.gov ID
- NCT03138421
- Acronym / sponsor ID
- ABX-1431_PN009
- Conditions
- Neuromyelitis Optica Spectrum Disorder, Transverse Myelitis, Multiple Sclerosis, Longitudinally Extensive Transverse Myelitis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Abide TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 23 Jul 2018 (actual)
- Study completion
- 24 Jul 2018 (actual)
- First posted
- 3 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ABX-1431 HCl | Experimental | Drug: ABX-1431 HCl |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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'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.
Key exclusion criteria (10 listed)
- 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:
- Patients taking daily oral opioid drugs are excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ABX-1431 HClABX-1431 HCl, capsules, 20 mg | Drug | ABX-1431 HCl |
| PlaceboMatching placebo | Drug | Placebo |
Primary outcome
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)
The treatment difference of ABX-1431 HCl versus placebo is estimated from the change from baseline in daily NRS-11 Pain to the final 7 days of treatment in each two-week treatment period. Baseline levels of pain or taken from the final 7 days of treatment in the period preceding each double-blind treatment period.
8 secondary outcomes
Short Form Brief Pain Inventory (SF-BPI) Scores
Time frame: placebo, treatment (14 days)
Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2)
Time frame: placebo, treatment (14 days)
Patient Global Impression of Change (PGIC) score
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)
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)
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)
ABX-11431 and metabolite M55 plasma PK
Time frame: placebo, treatment (14 days)
2-AG hydrolysis in PBMC
Time frame: placebo, treatment (14 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacqueline Palace, FRCP DM principal investigator
Oxford University Hospitals NHS Trust
Anu Jacob, MD DM FRCP principal investigator
The Walton Centre
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ABX-1431 HCl in people with Neuromyelitis Optica Spectrum Disorder and Transverse Myelitis, run by Abide Therapeutics at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2019; AzTrials last refreshed its copy on 28 Oct 2026.