Multiple-Dose Study to Evaluate the Safety and Efficacy of IXT-m200

Study Overview
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Brief Summary
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This Phase 2 study will evaluate the safety and efficacy of monthly intravenous doses of IXT-m200 in treatment-seeking individuals with methamphetamine (METH) use disorder. The hypothesis are that following an initial relapse, IXT-m200 will reduce the occurrence of stimulant-positive saliva samples compared to placebo and improve the signs and symptoms of METH Use Disorder (MUD).

Official Title
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A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Multiple-Dose Study to Evaluate the Safety and Efficacy of IXT-m200 in Treatment-Seeking Individuals With Methamphetamine Use Disorder

Conditions
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Methamphetamine-dependence, Methamphetamine Abuse

Intervention / Treatment
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* Drug: IXT-m200
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Eligible participants will: Be at least 18 years of age at the time of study consent; Meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for Substance Use Disorder associated with methamphetamine; Be treatment-seeking methamphetamine users with at least 1 methamphetamine or amphetamine positive specimen during the screening period; Be able and willing to read, comprehend, and give Authorization for Use/Disclosure of Health Information (HIPAA) and informed consent; Be willing to comply with study instructions and dosing, agree to make all appointments, and complete the entire course of the study; Agree to use protocol-specified method(s) of birth control throughout study participation; Agree to adhere to Lifestyle Considerations throughout study duration; Have access to a smartphone or other device capable of supporting the study app; Successfully complete app-based training program as evidenced by completion of at least 75% of daily drug use surveys and assigned saliva drug screens (two of which must be valid) in ≤30 days from the screening visit during the screening period. Eligible participants will NOT: Have current dependence, defined by DSM-5 criteria, on any psychoactive substance (i.e., opioids or benzodiazepines), other than methamphetamine or nicotine (any severity). Mild severity dependence on alcohol or marijuana is allowed; Be currently taking certain other drugs and medications, including: designer drugs (e.g., 3,4-methylenedioxyMETH (MDMA, Ecstasy, Adam, XTC) and its N-dimethyl metabolite methylenedioxyamphetamine (MDA), anti-orexigenic drugs (including over-the-counter medications for weight loss), or be chronic users of phenethylamine compounds (e.g., phenylpropanolamine, ephedrine, pseudoephedrine, amphetamine, phentermine, phenmetrazine, methylphenidate, diethylpropion, and propylhexedrine); Have a known contraindication or sensitivity to IXT-m200 based on known allergies to other monoclonal antibodies, any inactive ingredient of IXT-m200, or any other products required for the study procedures; Have a history of severe allergy (rash, hives, breathing difficulty, etc) to any medications; Have a history of allergic or environmental bronchial asthma within the past 3 years; Have a current diagnosis of anorexia nervosa or bulimia disorder; Have a history of unstable cardiovascular disease that is not adequately controlled at the time of eligibility determination; Be mandated by the court to obtain treatment for methamphetamine-dependence where such mandate required the results of methamphetamine testing to be reported to the court; Have positive saliva drug screens for psychoactive substances other than amphetamines at the screening visit; Be expected to fail to complete the study protocol due to probable incarceration or relocation from the clinic area, or any clinically significant mental or physical illness within a 1-year prior, that would impact compliance with trial requirements; Have clinically significant laboratory values (outside of normal limits). The following specified ranges are allowable: Liver function tests (total, direct, and indirect bilirubin, aspartate transaminase, alanine aminotransferase, gamma-glutamyl transferase, lactate dehydrogenase, and alkaline phosphatase) <3 times the upper limit of normal, and Kidney function tests (creatinine and BUN) <2 times the upper limit of normal; Be considered to be at imminent risk of suicide or have a past-year history of a serious suicide attempt (defined as an attempt that results in or requires medical treatment) based on response to queries within eligibility screening about suicidal ideation and attempts; Have an uncontrolled systemic disease or a medical condition that may increase the risk associated with study participation or administration of study treatment or that may interfere with the interpretation of study results; Be currently participating or has participated within the last 30 days prior to the start of this study in a drug, device, or other interventional research study; Be pregnant or lactating; In the Investigator's or Sponsor's (or designee) opinion, be inappropriate for the study, including those believed to be attempting to enter the study primarily for financial gain.

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IXT-m200<br>Anti-methamphetamine monoclonal antibody, dose levels of 1.5 and 3 g | Drug: IXT-m200<br>* IXT-m200 binds METH with high selectivity and affinity. The product contains a murine METH-binding variable region and the constant domains of a human immunoglobulin G (IgG) 2κ. This antibody isotype was chosen because of the lower risk of immune response compared to an IgG1 or IgG3. IXT-m200 targets METH, does not rely on binding to any endogenous target for its action, and has been well-tolerated in previous clinical studies.<br>|
| Placebo Comparator: Placebo<br>Saline | Other: Placebo<br>* Saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of 20 weeks abstinent from stimulants following a 4-week grace period | Saliva screens and by self-report | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of responders with reduced DSM-5 criteria at Week 25 as measured by DSM-5 criteria | A responder is defined as a participant who meets a reduced number of DSM-5 criteria for MUD over the past month compared to Screening | 25 weeks | 
| Proportion of responders in early remission at Week 25 as measured by DSM-5 criteria | A responder is defined as a participant who meets the definition of early remission, i.e., at least 3 months and <12 months without meeting DSM-5 criteria other than craving. | 25 weeks | 
| Complete abstinence during last month of study drug treatment | Saliva screens and by self-report | 25 weeks | 
| Difference between groups in Clinical Global Impression of Change (CGIC) at Week 13, 25, and 33 | The CGIC asks clinicians to complete one statement with the result ranging from 1-7 with lower scores representing a better outcome. | 33 weeks | 
| Difference between groups in Patient Global Impression of Change (PGIC) at Week 13, 25, and 33 | The PGIC asks patients to complete one statement with the result ranging from 1-7 with lower scores representing a better outcome. | 33 weeks | 
| Change from screening in participant-rated quality of life as measured by the Treatment Effectiveness Assessment | Treatment Effectiveness Assessment (TEA) asks questions in four domains with results ranging from 4-40 with higher scores representing a better outcome. | 33 weeks | 
| Number of treatment-related adverse events (AEs) as measured by physical examination | Physical examinations | 33 weeks | 
| Number of treatment-related AEs as measured by vital signs | Blood pressure, heart rate, and temperature | 33 weeks | 
| Number of treatment-related AEs as measured by ECG | Electrocardiogram | 33 weeks | 
| Number of treatment-related AEs as measured by clinical laboratory testing | Clinical laboratory testing | 33 weeks | 
| Number of participants with anti-IXT-m200 antibody levels that are confirmed positive and have titers more than three times the minimum required dilution | Anti-IXT-m200 antibody levels | 33 weeks |