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

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

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).

Study Overview

• Status: Terminated
• Conditions: Methamphetamine-dependence; Methamphetamine Abuse
• Intervention / Treatment: Other: Placebo; Drug: IXT-m200

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Pillar Clinical Research
    • Little Rock, Arkansas, United States, 72211
      • Woodlands International Research Group
  • California
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
  • Illinois
    • Lincolnwood, Illinois, United States, 60712
      • Pillar Clinical Research
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
  • Texas
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research
    • Houston, Texas, United States, 77008
      • HD Research
    • Richardson, Texas, United States, 75080
      • Pillar Clinical Research
  • Utah
    • Clinton, Utah, United States, 84015
      • Alpine Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Eligible participants will:

1. Be at least 18 years of age at the time of study consent;
2. Meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for Substance Use Disorder associated with methamphetamine;
3. Be treatment-seeking methamphetamine users with at least 1 methamphetamine or amphetamine positive specimen during the screening period;
4. Be able and willing to read, comprehend, and give Authorization for Use/Disclosure of Health Information (HIPAA) and informed consent;
5. Be willing to comply with study instructions and dosing, agree to make all appointments, and complete the entire course of the study;
6. Agree to use protocol-specified method(s) of birth control throughout study participation;
7. Agree to adhere to Lifestyle Considerations throughout study duration;
8. Have access to a smartphone or other device capable of supporting the study app;
9. 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:

1. 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;
2. 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);
3. 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;
4. Have a history of severe allergy (rash, hives, breathing difficulty, etc) to any medications;
5. Have a history of allergic or environmental bronchial asthma within the past 3 years;
6. Have a current diagnosis of anorexia nervosa or bulimia disorder;
7. Have a history of unstable cardiovascular disease that is not adequately controlled at the time of eligibility determination;
8. 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;
9. Have positive saliva drug screens for psychoactive substances other than amphetamines at the screening visit;
10. 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;

11. Have clinically significant laboratory values (outside of normal limits). The following specified ranges are allowable:

    1. 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
    2. Kidney function tests (creatinine and BUN) <2 times the upper limit of normal;
12. 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;
13. 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;
14. 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;
15. Be pregnant or lactating;
16. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Saline	Other: Placebo; Saline
Experimental: IXT-m200; Anti-methamphetamine monoclonal antibody, dose levels of 1.5 and 3 g	Drug: IXT-m200; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of 20 Weeks Abstinent From Stimulants Following a 4-week Grace Period	The difference in group means between the IXT-m200 and placebo groups for the percent of 20 weeks abstinent from stimulants following a 4-week grace period as measured by saliva screens in treatment-seeking individuals with Methamphetamine Use Disorder. All observations will be used, regardless of whether a participant discontinued treatment early. All missing values will be imputed assuming the participant is not abstinent.	20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Screening in Participant-rated Quality of Life as Measured by the Treatment Effectiveness Assessment at Week 13, 25, and 33.	Treatment Effectiveness Assessment (TEA) asks questions in four domains with results ranging from 4-40 with higher scores representing a better outcome.	Weeks 13, 25, and 33
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
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.	Weeks 13, 25, and 33
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.	Weeks 13, 25, and 33

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of sequential weeks of abstinence from the end of treatment	Saliva screens and by self-report	25 weeks
Point prevalence abstinence (last 7 days)	Saliva screens and by self-report	33 weeks
Weekly abstinence from stimulants following a 4-week grace period	Saliva screens	25 weeks
Proportion of responders with reduced DSM-5 criteria at Week 33 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	33 weeks
Proportion of responders in early remission at Week 33 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.	33 weeks

Collaborators and Investigators

• Sponsor: InterveXion Therapeutics, LLC
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Study Director: Chief Medical Officer, InterveXion Therapeutics

Publications and helpful links

Helpful Links

• OUTLASTstudy.com provides information about the trial for potential participants

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2022
• Primary Completion (Actual): September 11, 2023
• Study Completion (Actual): November 7, 2023

Study Registration Dates

• First Submitted: August 30, 2021
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): October 4, 2024
• Last Update Submitted That Met QC Criteria: September 24, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: M200C-2201; U01DA055481 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Final datasets are expected to contain IXT-m200 concentrations and immunogenicity results, METH use frequencies, Treatment Effectiveness Assessment scores, and safety data over time. No individually identifiable private information will be distributed.
• IPD Sharing Time Frame: These datasets will be available for distribution following submission to the FDA of the Clinical Study Report and publication. They will be available for 2 years after the initial publication.
• IPD Sharing Access Criteria: These datasets and associated documentation will be made available on CD by the Sponsor to requestors under a data sharing agreement that provides for: (1) a commitment to using the data only for research purposes; (2) a commitment to securing the data using appropriate computer technology and not distributing to third parties; and (3) a commitment to destroying or returning the data after analyses are completed. Requests should be sent to intervexion@gmail.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No