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

NCT04715230 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: M200C-2101U01DA053043
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

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)

Outcome Measures

Primary Outcomes (4)

• Number of Patients With Treatment-related Adverse Events (AEs) as Measured by Vital Signs

  Blood pressure, heart rate, and temperature

  28 days

• Number of Patients With Treatment-related AEs as Measured by Physical Examinations

  Physical examinations

  28 days

• Number of Patients With Treatment-related AEs as Measured by Clinical Laboratory Testing

  Clinical laboratory testing

  3 days

• Number of Patients With Treatment-related AEs as Measured by Electrocardiogram

  Electrocardiogram

  4 hours

Secondary Outcomes (5)

• Time Course and Degree of Normalization of Agitation

  Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.

• Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time

  Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.

• Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time

  Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.

• Time Course and Degree of Normalization of Temperature

  Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.

• Number of Participants Requiring Rescue Medications for Psychiatric or Cardiovascular Manifestations of METH Toxicity

  8 hours

Other Outcomes (1)

• Length of Patient Stay in the ED

  Start of treatment until discharge

Study Arms (2)

IXT-m200

EXPERIMENTAL

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.

Biological: IXT-m200

Treatment as Usual (TAU)

ACTIVE COMPARATOR

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.

Drug: Lorazepam; Drug: Haloperidol

Interventions

IXT-m200 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.

IXT-m200

Lorazepam DRUG

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

Treatment as Usual (TAU)

Haloperidol DRUG

Haloperidol is commonly used to treat agitation due to psychosis.

Treatment as Usual (TAU)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Be aged 18 to 45 years, inclusive;
• Present to the ED with METH toxicity as defined in protocol;
• Have a PANSS-EC score of 14-28, inclusive;
• Have or agrees to have an intravenous (IV) line placed;
• 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;
• Be accompanied or readily represented by a legally authorized representative (surrogate) who can consent to participation on behalf of the participant; and
• Assent to participation in the study.

You may not qualify if:

• Present with concomitant opioid overdose requiring ventilatory support;
• Be self-reported to be pregnant or lactating;
• Be considered to have significant concomitant medical illness or trauma, or symptoms of severe METH toxicity including
• sepsis or febrile illness;
• 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
• coma, stroke or severe head injury; new or ongoing seizure activity
• acute pulmonary decompensation or severe chronic obstructive pulmonary disease;
• any hepatic impairment and/or acute hepatitis or renal impairment due to concomitant medical illness; or
• current, or history of, neuroleptic malignant syndrome
• 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;
• Be considered to be at imminent risk of injury or danger to self, others or property;
• Have a history of severe allergy (rash, hives, breathing difficulty, etc.), known hypersensitivity or infusion reaction to any antibody medications, lorazepam or haloperidol; or
• 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.

Sponsors & Collaborators

• InterveXion Therapeutics, LLC: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (4)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

University of New Mexico Hospital

Albuquerque, New Mexico, 87106, United States

Location

Providence Regional Medical Center Everett

Everett, Washington, 98201, United States

Location

Sacred Heart Medical Center

Spokane, Washington, 99204, United States

Location

MeSH Terms

Interventions

Lorazepam; Haloperidol

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Butyrophenones; Ketones; Organic Chemicals

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Chief Operating Officer
• Organization: InterveXion Therapeutics

misty.stevens@intervexion.com

5015542377

Study Officials

• Chief Medical Officer

  InterveXion Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: January 20, 2021
• Study Start: June 30, 2021
• Primary Completion: October 5, 2022
• Study Completion: November 14, 2022
• Last Updated: November 18, 2023
• Results First Posted: November 18, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.
• 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

Locations

US (4)