Study of Antibody for Methamphetamine Outpatient Therapy

Study Overview
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Brief Summary
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This study evaluates the ability of IXT-m200 to change methamphetamine concentrations in blood and alter the way methamphetamine feels. Participants will receive either placebo, a low or high dose of IXT-m200, in addition to methamphetamine challenge doses.

Detailed Description
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IXT-m200 is a monoclonal antibody that binds to methamphetamine in the blood. The main purpose of this study is to look at the effects of IXT-m200 on the pharmacokinetics of methamphetamine and on methamphetamine liking effects. Additionally, the study will determine IXT-m200 pharmacokinetics, safety and tolerability in subjects with methamphetamine use disorder. Qualified subjects will receive a single dose of IXT-m200 followed by up to 4 methamphetamine challenge doses.

Official Title
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STAMPOUT: Study of Antibody for Methamphetamine Outpatient Therapy

Conditions
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Methamphetamine-dependence, Methamphetamine Abuse

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject voluntarily agrees to participate in this study and signs an informed consent form. Subject must be able to verbalize understanding of the consent forms, provide written informed consent, and verbalize willingness to complete study procedures. Males or females between 21 to 50 years of age, inclusive. Female subjects should be of non-childbearing potential or, they should be nonpregnant, nonlactating, and agree to use medically acceptable forms of birth control from screening to end-of-study follow-up, or have a partner who has had a vasectomy. Male subjects need to have had a vasectomy or agree to use a condom and spermicide in addition to their female partners using a form of birth control. They should agree not to donate sperm for 90 days post IXT-m200 dose. Body mass index (BMI) between 18.0 and 35.0 kg/m2. Body weight ≥ 50 kg and ≤ 100 kg. Subjects have hematology and chemistry laboratory tests that are within normal (+/- 10%) limits with the following exceptions: a) liver function tests (total bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) < 3 times the upper limit of normal, and b) kidney function tests (creatinine and BUN) < 2 times the upper limit of normal. Subjects meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for METH use disorder and are not seeking treatment at the time of the study. Subjects will be experienced METH users with a history of non-therapeutic METH use for 2 or more years. Subjects must have experience with smoking or IV injection of METH. Current METH use (past 30 days) less than daily, self-reported and documented by calendar-based timeline follow-back. Primary current (past 30 days) route of METH self-administration other than IV (ie, smoking, snorting, or oral). Subjects agree not to take METH from any source outside of the study during their participation in the study. Subjects agree not to take substances that are structurally similar to METH. Subjects must provide a negative urine sample prior to admission to the unit on Day -1 for the study. Exclusion Criteria: Subjects who have been treated with a monoclonal antibody (mAb) in the past year. Known or suspected allergy sensitivity to IXT-m200 based on known allergies to other mAbs. History of severe allergy (rash, hives, breathing difficulty, etc) to any medications. History of allergic or environmental bronchial asthma. Clinically significant history of or current abnormality or disease of any organ system, including renal, hepatic, GI, cardiovascular, pulmonary (including chronic asthma), endocrine (eg, diabetes), central nervous, or hematologic systems, or recent clinically significant surgery. Current diagnosis or history of major psychiatric illness in the past two years or other current psychiatric condition requiring medication, other than methamphetamine dependence. Considered by the PI to be at imminent risk of suicide or injury to self, others, or property, or the subject has attempted suicide with the past year. Past year history of, or current evidence for, suicidal ideation or those who were actively suicidal based on the Columbia-Suicide Severity Rating Scale (C-SSRS). Current dependence on alcohol or heavy use defined as >28 alcoholic drinks per week if male and >21 drinks per week if female in last 30 days. Current dependence on other drugs except amphetamines, or marijuana and nicotine used in moderate amounts. History of seizure, epilepsy, severe head injury with residual neurologic effects, multiple sclerosis, or stroke. Abnormal pre-admission vital signs, physical examination, clinical laboratory, ECG, or any safety variable which is considered clinically significant for this population. History of cardiovascular disease. Treatment with any prescription medications or over the counter nutritional supplements within 14 days prior to the first dose of study medication. Ingestion of any approved prescription anti-obesity drug or taken any over-the-counter medication for weight loss within a period of 90 days prior to the first dose of study medication. Ingestion or use of any investigational medication or device within 30 days prior to the first dose of study medication. Acute illness within 5 days prior to the first dose of study medication, eg, flu syndrome, GI virus, or clinically significant indigestion (eg, reflux). Positive result for hepatitis B surface antigen (HBsAG), hepatitis C (HepC) antibody, hepatitis A immunoglobulin M (IgM), or HIV Viral Serology, or nucleic acid testing (NAT) tests at screening. Positive breath alcohol test or positive urine drug test for illicit substances on Day -1. Subjects with history of donated blood, plasma, or platelets in last 30 days, and who do not agree to refrain from blood, plasma, platelets, egg or sperm donation during the study period. Predominant or only route of METH self-administration is IV. Any subject judged by the PI or Sponsor (or designee) to be inappropriate for the study.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Normal saline | Drug: Placebo<br>* Normal saline<br>|
| Experimental: IXT-m200<br>Single 6 or 20 mg/kg intravenous dose of IXT-m200 | Drug: IXT-m200<br>* IXT-m200 is an anti-methamphetamine monoclonal antibody<br>* Other names: ch-mAb7F9;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | METH AUCinf following IXT-m200 dosing on each METH Challenge Day. | Day 1, 5, 12, 19, and 26 | 
| Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | METH Cmax following IXT-m200 dosing on each METH Challenge Day. | Day 1, 5, 12, 19, and 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Subjective Effects for CRAVE of METH Challenge Doses | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for CRAVE over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). | Day 1, 5, 12, 19, and 26 | 
| Change in Subjective Effects for DISLIKE of METH Challenge Doses | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for DISLIKE over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). | Day 1, 5, 12, 19, and 26 | 
| Change in Subjective Effects for FEEL of METH Challenge Doses | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for FEEL over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). | Day 1, 5, 12, 19, and 26 | 
| Change in Subjective Effects for GOOD of METH Challenge Doses | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for GOOD over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). | Day 1, 5, 12, 19, and 26 | 
| Change in Subjective Effects for HIGH of METH Challenge Doses | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for HIGH over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). | Day 1, 5, 12, 19, and 26 | 
| Change in Subjective Effects for LIKE of METH Challenge Doses | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for LIKE over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). | Day 1, 5, 12, 19, and 26 | 
| Change in Subjective Effects for MORE of METH Challenge Doses | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for MORE over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). | Day 1, 5, 12, 19, and 26 | 
| Change in Subjective Effects for STIMULATED of METH Challenge Doses | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for STIMULATED over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). | Day 1, 5, 12, 19, and 26 | 
| Safety and Tolerability of IXT-m200 Followed by METH Challenges | Number of serious adverse events (SAEs) as identified by physical examinations and vital sign, adverse event, ECG, and clinical laboratory testing, and immune response by measurement of anti-IXT-m200 antibody levels. | 126 days | 
| Pharmacokinetics of IXT-m200 Following Single Administration | Measured by serum concentrations of IXT-m200 over time | 122 days |