Methamphetamine Abuse, Methamphetamine-dependence
Conditions
Brief summary
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).
Interventions
DRUGIXT-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.
OTHERPlacebo
Saline
Sponsors
National Institute on Drug Abuse (NIDA)
InterveXion Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of 20 Weeks Abstinent From Stimulants Following a 4-week Grace Period | 20 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Screening in Participant-rated Quality of Life as Measured by the Treatment Effectiveness Assessment at Week 13, 25, and 33. | Weeks 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. |
| Proportion of Responders in Early Remission at Week 25 as Measured by DSM-5 Criteria | 25 weeks | 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. |
| Difference Between Groups in Clinical Global Impression of Change (CGIC) at Week 13, 25, and 33 | Weeks 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. |
| Difference Between Groups in Patient Global Impression of Change (PGIC) at Week 13, 25, and 33 | Weeks 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. |
Countries
United States
Participant flow
Pre-assignment details
Patients were required to qualify for the study by complying with app-based drug testing assignments. In addition, one of the drug tests performed during the screening period must have been positive for methamphetamine (METH) to qualify.
Participants by arm
| Arm | Count |
|---|---|
| IXT-m200 Anti-methamphetamine monoclonal antibody, dose level of 1.5 g
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. | 41 |
| Placebo Saline
Placebo: Saline | 20 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 18 | 8 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Skipped final visits, checked into rehab | 2 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 6 |
Baseline characteristics
| Characteristic | Placebo | IXT-m200 | Total |
|---|---|---|---|
| Age, Continuous | 46.8 years STANDARD_DEVIATION 7.63 | 41.2 years STANDARD_DEVIATION 10.13 | 43.0 years STANDARD_DEVIATION 9.7 |
| Days per month of METH use <18 days per month | 1 participants | 2 participants | 3 participants |
| Days per month of METH use ≥18 days per month | 19 participants | 39 participants | 58 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 6 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 35 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 18 Participants | 38 Participants | 56 Participants |
| Sex: Female, Male Female | 10 Participants | 26 Participants | 36 Participants |
| Sex: Female, Male Male | 10 Participants | 15 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 20 |
| other Total, other adverse events | 21 / 41 | 8 / 20 |
| serious Total, serious adverse events | 3 / 41 | 2 / 20 |
Outcome results
Primary
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.
Time frame: 20 weeks
Population: Intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IXT-m200 | Percent of 20 Weeks Abstinent From Stimulants Following a 4-week Grace Period | 5.9 percentage of 20 weeks abstinent | Standard Deviation 17.33 |
| Placebo | Percent of 20 Weeks Abstinent From Stimulants Following a 4-week Grace Period | 4.3 percentage of 20 weeks abstinent | Standard Deviation 8.73 |
Secondary
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.
Time frame: Weeks 13, 25, and 33
Population: Intent to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IXT-m200 | Change From Screening in Participant-rated Quality of Life as Measured by the Treatment Effectiveness Assessment at Week 13, 25, and 33. | Week 13 | 6.2 score on a scale | Standard Deviation 8.67 |
| IXT-m200 | Change From Screening in Participant-rated Quality of Life as Measured by the Treatment Effectiveness Assessment at Week 13, 25, and 33. | Week 25 | 7.3 score on a scale | Standard Deviation 9.07 |
| IXT-m200 | Change From Screening in Participant-rated Quality of Life as Measured by the Treatment Effectiveness Assessment at Week 13, 25, and 33. | Week 33 | 11 score on a scale | Standard Deviation 9.32 |
| Placebo | Change From Screening in Participant-rated Quality of Life as Measured by the Treatment Effectiveness Assessment at Week 13, 25, and 33. | Week 13 | 4.6 score on a scale | Standard Deviation 8.16 |
| Placebo | Change From Screening in Participant-rated Quality of Life as Measured by the Treatment Effectiveness Assessment at Week 13, 25, and 33. | Week 25 | 17 score on a scale | Standard Deviation 9.09 |
| Placebo | Change From Screening in Participant-rated Quality of Life as Measured by the Treatment Effectiveness Assessment at Week 13, 25, and 33. | Week 33 | 13.5 score on a scale | Standard Deviation 10.25 |
Secondary
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.
Time frame: Weeks 13, 25, and 33
Population: Intent to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IXT-m200 | Difference Between Groups in Clinical Global Impression of Change (CGIC) at Week 13, 25, and 33 | Week 13 | 3 score on a scale | Standard Deviation 1.11 |
| IXT-m200 | Difference Between Groups in Clinical Global Impression of Change (CGIC) at Week 13, 25, and 33 | Week 25 | 3.1 score on a scale | Standard Deviation 0.89 |
| IXT-m200 | Difference Between Groups in Clinical Global Impression of Change (CGIC) at Week 13, 25, and 33 | Week 33 | 2.7 score on a scale | Standard Deviation 1.28 |
| Placebo | Difference Between Groups in Clinical Global Impression of Change (CGIC) at Week 13, 25, and 33 | Week 13 | 3 score on a scale | Standard Deviation 0.87 |
| Placebo | Difference Between Groups in Clinical Global Impression of Change (CGIC) at Week 13, 25, and 33 | Week 25 | 2.3 score on a scale | Standard Deviation 0.96 |
| Placebo | Difference Between Groups in Clinical Global Impression of Change (CGIC) at Week 13, 25, and 33 | Week 33 | 2 score on a scale | Standard Deviation 0.82 |
Secondary
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.
Time frame: Weeks 13, 25, and 33
Population: Intent to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IXT-m200 | Difference Between Groups in Patient Global Impression of Change (PGIC) at Week 13, 25, and 33 | Week 13 | 2.8 score on a scale | Standard Deviation 1.22 |
| IXT-m200 | Difference Between Groups in Patient Global Impression of Change (PGIC) at Week 13, 25, and 33 | Week 25 | 3 score on a scale | Standard Deviation 1.55 |
| IXT-m200 | Difference Between Groups in Patient Global Impression of Change (PGIC) at Week 13, 25, and 33 | Week 33 | 2.3 score on a scale | Standard Deviation 1.39 |
| Placebo | Difference Between Groups in Patient Global Impression of Change (PGIC) at Week 13, 25, and 33 | Week 13 | 3 score on a scale | Standard Deviation 0.87 |
| Placebo | Difference Between Groups in Patient Global Impression of Change (PGIC) at Week 13, 25, and 33 | Week 25 | 2.5 score on a scale | Standard Deviation 1.29 |
| Placebo | Difference Between Groups in Patient Global Impression of Change (PGIC) at Week 13, 25, and 33 | Week 33 | 1.8 score on a scale | Standard Deviation 0.96 |
Secondary
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.
Time frame: 25 weeks
Population: Intent to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IXT-m200 | Proportion of Responders in Early Remission at Week 25 as Measured by DSM-5 Criteria | 2.4 percentage of responders |
| Placebo | Proportion of Responders in Early Remission at Week 25 as Measured by DSM-5 Criteria | 0 percentage of responders |