Meth-OD: A Study of IXT-m200 in Patients With Toxicity From Methamphetamine Overdose

NCT ID: NCT04715230

Last Updated: 2023-11-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-30
• Study Completion Date: 2022-11-14

Brief Summary

The hypothesis of this multisite Phase 2a study is that IXT-m200 will be well-tolerated in patients with acute mild to moderate METH toxicity. A randomized, open label design will be used in which one dose of IXT-m200 will be compared to treatment-as-usual (TAU). Approximately 40 participants will be enrolled in 4 cohorts. A dose escalation approach will be used so that progressively higher IXT-m200 doses will be evaluated in each cohort. In conjunction with safety monitoring, this design assures the opportunity to observe early safety findings before any participants are exposed to the next higher dose. The randomization ratio for IXT-m200 versus TAU is defined as 4:1 for each cohort so that the number of participants receiving TAU equals the number receiving each dose of IXT-m200 at the end of the study.

Agitation scales and vital signs will be recorded to track effect of the antibody treatment versus TAU over time on agitation associated with METH use. While in the emergency department (ED), detailed and pertinent medical and psychiatric histories, and physical exam will be obtained, along with laboratory assessments and ECGs. In the ED, participants will give blood samples for analysis of METH and IXT-m200 concentrations and followed for development of adverse events. Participants will be evaluated at 2 days and 4 weeks after discharge from the ED for adverse events and drug use history. Cohort escalation reviews will be performed by the Sponsor, Medical Monitor, and Data and Safety Monitoring Board (DSMB) between cohorts and the next group will not start until after completion of this review.

Conditions

Methamphetamine Intoxication (Disorder)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IXT-m200

IXT-m200 is a high-affinity chimeric anti-METH monoclonal antibody that is well-tolerated in healthy volunteers and in non-intoxicated people with METH use disorder. The total dose will be given over 10 min for the 0.5-g dose and over 20 min for the 1-, 1.5-, and 2-g doses.

Group Type: EXPERIMENTAL

IXT-m200

Intervention Type: BIOLOGICAL

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.

Treatment as Usual (TAU)

Lorazepam is a benzodiazepine that is safe and commonly used to treat agitation and dysphoria in the emergency setting. Haloperidol is commonly used to treat agitation due to psychosis.

Group Type: ACTIVE_COMPARATOR

Lorazepam

Intervention Type: DRUG

Lorazepam is a benzodiazepine that is safe and commonly used to treat agitation and dysphoria in the emergency setting.

Haloperidol

Intervention Type: DRUG

Haloperidol is commonly used to treat agitation due to psychosis.

Interventions

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.

Intervention Type: BIOLOGICAL

Lorazepam

Lorazepam is a benzodiazepine that is safe and commonly used to treat agitation and dysphoria in the emergency setting.

Intervention Type: DRUG

Haloperidol

Haloperidol is commonly used to treat agitation due to psychosis.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Be aged 18 to 45 years, inclusive;

2. Present to the ED with METH toxicity as defined in protocol;

3. Have a PANSS-EC score of 14-28, inclusive;

4. Have or agrees to have an intravenous (IV) line placed;

5. Give a history of METH use in the past 24 hours, with participant or observer attribution of symptoms to METH, or have a positive METH drug screen;

6. Be accompanied or readily represented by a legally authorized representative (surrogate) who can consent to participation on behalf of the participant; and

7. Assent to participation in the study.

Exclusion Criteria

1. Present with concomitant opioid overdose requiring ventilatory support;

2. Be self-reported to be pregnant or lactating;

3. Be considered to have significant concomitant medical illness or trauma, or symptoms of severe METH toxicity including

1. sepsis or febrile illness;

2. myocardial infarction, cardiac decompensation or arrhythmias including tachycardia that is not sinus; severe hypertension (>180/110 mmHg); inadequately treated hypertension on chronic medication; history of vasculitis

3. coma, stroke or severe head injury; new or ongoing seizure activity

4. acute pulmonary decompensation or severe chronic obstructive pulmonary disease;

5. any hepatic impairment and/or acute hepatitis or renal impairment due to concomitant medical illness; or

6. current, or history of, neuroleptic malignant syndrome

4. Be considered to be at imminent risk of suicide or have disqualifying answers to the following two questions. Disqualifying answers would be 1b2 or 2b. 1. In the past 30 days, have you considered killing yourself? a) No; b) Yes - if Yes, how often? b1) Not often (twice or less), b2) Somewhat often (more than twice). 2. In the past year, have you attempted to kill yourself? a) No; b) Yes;

5. Be considered to be at imminent risk of injury or danger to self, others or property;

6. Have a history of severe allergy (rash, hives, breathing difficulty, etc.), known hypersensitivity or infusion reaction to any antibody medications, lorazepam or haloperidol; or

7. Be judged by the treating ED physician, investigator, or Sponsor (or designee) to be inappropriate for the study, including people whom the investigator determines cannot reasonably be consulted for assent to participation.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

InterveXion Therapeutics, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chief Medical Officer

Role: STUDY_DIRECTOR

InterveXion Therapeutics

Locations

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

University of New Mexico Hospital

Albuquerque, New Mexico, United States

Providence Regional Medical Center Everett

Everett, Washington, United States

Sacred Heart Medical Center

Spokane, Washington, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

U01DA053043

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M200C-2101

Identifier Type: -

Identifier Source: org_study_id