Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| U01DA053043 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Sponsor decision based on slower than anticipated enrollment leading to fund exhaustion.
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Time Course and Degree of Normalization of Agitation | Agitation/sedation scores over time as measured by Agitation/Calmness Evaluation Score (ACES). The minimum value is 1 (highly agitated) and the highest value is 9 (completely sedated). A score of 3-5 is considered normal. | Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge. |
| Measure | Description | Time Frame |
|---|---|---|
| Length of Patient Stay in the ED | ED length of stay as measured by discharge time minus start of treatment time | Start of treatment until discharge |
Inclusion Criteria:
Exclusion Criteria:
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
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Chief Medical Officer | InterveXion Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arkansas for Medical Sciences | Little Rock | Arkansas | 72205 | United States | ||
| University of New Mexico Hospital |
Final datasets are expected to contain IXT-m200 and METH concentration data, ACES scores over time, and safety data. No individually identifiable private information will be distributes.
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.
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
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | IXT-m200 Low Dose (0.5 g) | 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. 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. |
| FG001 | IXT-m200 High Dose (2 g) | 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 20 min for the 2-g doses. 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. |
| FG002 | 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. Lorazepam: Lorazepam is a benzodiazepine that is safe and commonly used to treat agitation and dysphoria in the emergency setting. Haloperidol: Haloperidol is commonly used to treat agitation due to psychosis. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | IXT-m200 Low Dose (0.5 g) | 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. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients With Treatment-related Adverse Events (AEs) as Measured by Vital Signs | Blood pressure, heart rate, and temperature | All participants receiving a dose of IXT-m200 or TAU. | Posted | Count of Participants | Participants | 28 days |
|
28 days
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | IXT-m200 Low Dose (0.5 g) | 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. 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Mass | General disorders | MedDRA (25.0) | Non-systematic Assessment | Orbital Mass |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Agitation | Psychiatric disorders | MedDRA (25.0) | Non-systematic Assessment |
Early termination leading to small numbers of subjects analyzed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Operating Officer | InterveXion Therapeutics | 5015542377 | misty.stevens@intervexion.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 22, 2022 | Sep 18, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 17, 2023 | Sep 20, 2023 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 29, 2022 | Sep 20, 2023 | ICF_002.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D008140 | Lorazepam |
| D006220 | Haloperidol |
| ID | Term |
|---|---|
| D001570 | Benzodiazepinones |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Lorazepam | Drug | Lorazepam is a benzodiazepine that is safe and commonly used to treat agitation and dysphoria in the emergency setting. |
|
| Haloperidol | Drug | Haloperidol is commonly used to treat agitation due to psychosis. |
|
| Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Blood pressure over time; reported as the number of participants with blood pressure out of normal range (i.e., diastolic >110 or <50 mmHg, or systolic >180 or <90 mmHg)) | 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 | Heart rate over time reported as number of participants with heart rate high (>120 beats/min), normal, or low (<40 beats/min). | Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge. |
| Time Course and Degree of Normalization of Temperature | Temperature over time | 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 | Number of participants that need rescue medications to treat:
| 8 hours |
| Albuquerque |
| New Mexico |
| 87106 |
| United States |
| Providence Regional Medical Center Everett | Everett | Washington | 98201 | United States |
| Sacred Heart Medical Center | Spokane | Washington | 99204 | United States |
| BG001 | IXT-m200 High Dose (2 g) | 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 20 min for the 2-g doses. 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. |
| BG002 | 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. Lorazepam: Lorazepam is a benzodiazepine that is safe and commonly used to treat agitation and dysphoria in the emergency setting. Haloperidol: Haloperidol is commonly used to treat agitation due to psychosis. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | IXT-m200 High Dose (2 g) | 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 20 min for the 2-g doses. 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. |
| OG002 | 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. Lorazepam: Lorazepam is a benzodiazepine that is safe and commonly used to treat agitation and dysphoria in the emergency setting. Haloperidol: Haloperidol is commonly used to treat agitation due to psychosis. |
|
|
| Primary | Number of Patients With Treatment-related AEs as Measured by Physical Examinations | Physical examinations | All participants receiving a dose of IXT-m200 or TAU | Posted | Count of Participants | Participants | 28 days |
|
|
|
| Primary | Number of Patients With Treatment-related AEs as Measured by Clinical Laboratory Testing | Clinical laboratory testing | All participants receiving a dose of IXT-m200 or TAU. | Posted | Count of Participants | Participants | 3 days |
|
|
|
| Primary | Number of Patients With Treatment-related AEs as Measured by Electrocardiogram | Electrocardiogram | All participants receiving a dose of IXT-m200 or TAU. | Posted | Count of Participants | Participants | 4 hours |
|
|
|
| Secondary | Time Course and Degree of Normalization of Agitation | Agitation/sedation scores over time as measured by Agitation/Calmness Evaluation Score (ACES). The minimum value is 1 (highly agitated) and the highest value is 9 (completely sedated). A score of 3-5 is considered normal. | All participants receiving a dose of IXT-m200 or TAU. No further data were collected after participants were discharged. Some time points do not contain results as all participants in that group had been discharged prior to that timepoint or all data were missing. | Posted | Mean | Standard Deviation | score on a scale | Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge. |
|
|
|
| Secondary | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Blood pressure over time; reported as the number of participants with blood pressure out of normal range (i.e., diastolic >110 or <50 mmHg, or systolic >180 or <90 mmHg)) | All participants receiving a dose of IXT-m200 or TAU. No further data were collected after participants were discharged. Some time points do not contain results as all participants in that group had been discharged prior to that timepoint or all data were missing. | Posted | Count of Participants | Participants | Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge. |
|
|
|
| Secondary | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Heart rate over time reported as number of participants with heart rate high (>120 beats/min), normal, or low (<40 beats/min). | All participants receiving a dose of IXT-m200 or TAU. No further data were collected after participants were discharged. Some time points do not contain results as all participants in that group had been discharged prior to that timepoint or all data were missing. | Posted | Count of Participants | Participants | Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge. |
|
|
|
| Secondary | Time Course and Degree of Normalization of Temperature | Temperature over time | All participants receiving a dose of IXT-m200 or TAU. No further data were collected after participants were discharged. Some time points do not contain results as all participants in that group had been discharged prior to that timepoint or all data were missing. | Posted | Mean | Standard Deviation | degrees Fahrenheit | Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge. |
|
|
|
| Secondary | Number of Participants Requiring Rescue Medications for Psychiatric or Cardiovascular Manifestations of METH Toxicity | Number of participants that need rescue medications to treat:
| All participants receiving a dose of IXT-m200 or TAU. | Posted | Count of Participants | Participants | 8 hours |
|
|
|
| Other Pre-specified | Length of Patient Stay in the ED | ED length of stay as measured by discharge time minus start of treatment time | All participants receiving a dose of IXT-m200 or TAU. | Posted | Mean | Standard Deviation | hours | Start of treatment until discharge |
|
|
|
| 0 |
| 8 |
| 1 |
| 8 |
| 5 |
| 8 |
| EG001 | IXT-m200 High Dose (2 g) | 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 20 min for the 2-g doses. 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. | 0 | 8 | 0 | 8 | 2 | 8 |
| EG002 | 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. Lorazepam: Lorazepam is a benzodiazepine that is safe and commonly used to treat agitation and dysphoria in the emergency setting. Haloperidol: Haloperidol is commonly used to treat agitation due to psychosis. | 0 | 4 | 0 | 4 | 2 | 4 |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (25.0) | Non-systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA (25.0) | Non-systematic Assessment | Increased liver enzymes and ongoing bilirubin |
|
| Hallucination, auditory | Psychiatric disorders | MedDRA (25.0) | Non-systematic Assessment |
|
| Hallucinations, mixed | Psychiatric disorders | MedDRA (25.0) | Non-systematic Assessment |
|
| Suicidal ideation | Psychiatric disorders | MedDRA (25.0) | Non-systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA (25.0) | Non-systematic Assessment |
|
| Pyelonephritis | Infections and infestations | MedDRA (25.0) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (25.0) | Non-systematic Assessment |
|
| Skin laceration | Injury, poisoning and procedural complications | MedDRA (25.0) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (25.0) | Non-systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (25.0) | Non-systematic Assessment |
|
PI must provide Sponsor opportunity to review proposed publications/disclosures before submission/disclosure. The first publication is to be a joint publication involving all sites, with Sponsor in control of such publication. Afterward, and if such publication is not made within 12 months following finalization of the clinical study report or termination of the study at all sites, PI may publish separately.
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D002090 | Butyrophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |
| 0.5 hour |
|
|
| 1 hour |
|
|
| 2 hours |
|
|
| 3 hours |
|
|
| 4 hours |
|
|
| Normal |
|
| Low |
|
| 0.5 hour |
|
|
| 1 hour |
|
|
| 2 hours |
|
|
| 3 hours |
|
|
| Prior to discharge |
|
|
| Normal |
|
| Low |
|
| 0.5 hour |
|
|
| 1 hour |
|
|
| 2 hours |
|
|
| 3 hours |
|
|
| Prior to discharge |
|
|
| 0.5 hour |
|
|
| 1 hour |
|
|
| 2 hours |
|
|
| 3 hours |
|
|
| Discharge |
|
|