Safety and Efficacy of XT-150 for Treatment of Neuropathic Pain

Study Overview
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Brief Summary
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Preliminary Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of Neuropathic Pain. Intrathecally administered, single injection.

Detailed Description
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XT-150 has been safe and well tolerated in clinical studies of intra-articular knee injections for osteoarthritis. This is the initial study of XT-150 for treatment of neuropathic pain. For this indication XT-150 must be administered by intrathecal injection. Doses used in the osteoarthritis studies will be studied for neuropathic pain. Upon safety reviews, doses will be increased by cohorts. The study is placebo controlled and blinded.

Official Title
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A Double Blind, Placebo Controlled, Preliminary Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of Neuropathic Pain

Conditions
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Neuropathic Pain

Intervention / Treatment
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* Biological: XT-150
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form Male or female, between 18 and 80 years of age, inclusive Clinical indication: Lumbar disk disease with no prior lumbar surgery with radicular pain symptoms and/or signs of compressive neuropathy At screening and baseline, a pain intensity score > 60 using the visual analog scale of pain intensity [VASPI] (0-100 mm scale) and a participant reported history of pain in the past 3 or more months Medically stable as determined by the Principal Investigator in consultation with the Sponsor's Medical Monitor, based on pre-study medical history, physical examination, and clinical laboratory tests In the judgment of the Principal Investigator, acceptable vital signs: blood pressure; resting heart rate; respirations, and oral temperature Life expectancy >6 months as determined by the Principal Investigator Female participants of child-bearing potential, and those <1 year post-menopausal, must be practicing highly effective methods of birth control such as hormonal methods (e.g., combined oral, implantable, injectable, or transdermal contraceptives), double barrier methods (e.g., condoms, sponge, diaphragm, or vaginal ring plus spermicidal jellies or cream), or total abstinence from heterosexual intercourse for a minimum of 1 full menstruation cycle before study drug administration and agree to continue abstinence for 1 full menstruation cycle after the study is completed Male participants who are heterosexually active, and not surgically sterile, must agree to use effective contraception for the duration of the study and for 1 month after the study is completed Stable medical regimen for ≥1 month before screening assessments Have suitable lumbar anatomy for intrathecal injection as determined by MRI or X-Ray in the last 6 months. Willing and able to return for the follow-up (FU) visits Able to read and understand study instructions, and willing and able to comply with all study procedures Adequately informed of the nature and risks of the study and give written informed consent before receiving any study specific assessments or procedures Stable use of non-prescription pain therapy, including massage, TENS, physiotherapy osteopathy, chiropractic and acupuncture for 2 months prior and throughout the study period Exclusion Criteria: Participants must NOT meet any of the following exclusion criteria: Hypersensitivity, allergy, or significant reaction to any ingredient of the study drug Any spinal deformity preventing intrathecal injection or making intrathecal injection unsafe Prior history of lumbar surgery, including fusion and microdiscectomy History of epidural block or facet block or steroid injection in the last 6 months Current unstable angina, uncontrolled congestive heart failure, or >1+ pitting edema of lower extremities History of acute myocardial infarction, transient ischemic attack, stroke, or seizure within 3 months of screening visit Severe chronic obstructive or restrictive pulmonary disease Current insulin dependent diabetes mellitus Current autoimmune conditions or documented immunodeficiency History of immunosuppressive therapy; high-potency systemic steroids in the last 3 months Current treatment with systemic immunosuppressive (systemic corticosteroid therapy [equivalent to >10mg/day prednisone] or other strong immunosuppressant) Current or history of central nervous system cancer Any malignancy (EXCEPTION: localized non-melanoma skin cancers) within 5 years before the screening visit or currently receiving systemic chemotherapy, radiation therapy, or a surgical stabilization procedure Significant hepatic disease as indicated by clinical laboratory results for the following: ≥3 times the upper limit of normal (ULN) for aspartate aminotransferase, alanine aminotransferase, ≥ 2.5 time ULN alkaline phosphatase, or ≥1.5 times ULN for total bilirubin) Severe anemia (Grade 3; hemoglobin <8.0 g/dL, <4.9 mmol/L, <80 g/L; transfusion indicated), Grade 1 white cell counts (lymphocytes <LLN - 800/mm3; <LLN - 0.8 x 109 /L, neutrophils <LLN - 1500/mm3; <LLN - 1.5 x 109 /L) Significant renal disease as indicated by creatinine ≥1.5 times the upper limit of normal or creatinine clearance <80 mL/minute (Cockcroft-Gault formula estimate) Confirmed positive for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus Significant psychological conditions; dementia, major depression, or altered mental state that in the opinion of the Investigator will interfere with study participation Current treatment with systemic antibiotics or antivirals (EXCEPTION: topical treatments) Current treatment with anticoagulants /antiplatelet medications except for low dose aspirin or low dose aspirin-containing compounds. Participants, if medically feasible, can interrupt anticoagulant therapy by following local medical practice protocol for intrathecal injections for participants on anticoagulant, antiplatelet therapy. Current use of systemic corticosteroids (equivalent to >10mg/day prednisone) Known or suspected history of active alcohol or illicit drug abuse within 1 year before the screening visit Women who are pregnant or nursing Use of any investigational drug or device within 1 month before randomization or current participation in a trial that included intervention with a drug or device; or currently participating in an investigational drug or device study Any condition that, in the opinion of the Principal Investigator, could compromise the safety of the participants, the participant's ability to communicate the study staff, or the quality of the data Presence of an implanted intrathecal infusion system or peripheral neurostimulator Presence of a generalized pain disorder such as fibromyalgia or complex regional pain syndrome that in the opinion of the PI may impact on evaluation of response to the study drug Diagnosis of peripheral neuropathy of the lower extremities which in the opinion of the PI, might interfere with the participant's ability to assess the effect of the study drug on the radicular signs and/or symptoms

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Dose escalation by cohort following safety reviews
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.015 milligram (mg) XT-150<br>0.015 mg of XT-150. Cohort 1 of the study | Biological: XT-150<br>* Single bolus intrathecal injection<br>* Other names: IL-10 transgene plasmid DNA injected intrathecally;|
| Experimental: 0.15 mg XT-150<br>0.15 mg of XT-150. Cohort 2 of the study | Biological: XT-150<br>* Single bolus intrathecal injection<br>* Other names: IL-10 transgene plasmid DNA injected intrathecally;|
| Experimental: 0.45 mg XT-150<br>0.45 mg of XT-150. Cohort 3 of the study | Biological: XT-150<br>* Single bolus intrathecal injection<br>* Other names: IL-10 transgene plasmid DNA injected intrathecally;|
| Placebo Comparator: Placebo<br>PBS for injection. | Biological: Placebo<br>* Placebo is a sterile phosphate-buffered saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Treatment-Emergent Adverse Events and Serious Adverse Events |  | 6 months | 
| Number of participants with abnormal vital signs |  | 6 months | 
| Number of participants with clinically significant abnormal physical examination findings |  | 6 months | 
| Number of participants with anti-interleukin (IL)-10 antibodies |  | 6 months | 
| Number of participants with IL-10 Protein |  | 6 months | 
| Number of participants with abnormal clinical and hematology parameters |  | 6 months | 
| Number of participants with plasmid DNA present in whole blood |  | 6 months | 
| Number of participants with cytokines in Cerebrospinal fluid |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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XT-150, Plasmid Gene Therapy, IL-10