E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post-traumatic stress disorder (PTSD) |
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E.1.1.1 | Medical condition in easily understood language |
Post-traumatic stress disorder, PTSD, trauma |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The overall objective of this study is to use standard clinical measures to explore the safety and effects of open-label manualized MDMA-assisted psychotherapy with a flexible dose of MDMA in participants with severe PTSD, and to serve as an opportunity for supervision of therapy teams selected to conduct Phase 3 MDMA-assisted psychotherapy research.
The primary objective of this study is to evaluate the effectiveness of MDMA-assisted psychotherapy for treatment of PTSD, as measured by the estimand of change in CAPS-5 Total Severity Score |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the effectiveness of MDMA-assisted psychotherapy for PTSD in clinician-rated functional impairment, as measured by the mean change in Sheehan Disability Scale (SDS) item scores.
Safety Objective The overall safety objective is to assess severity, incidence and frequency of AEs, AEs of Special Interest (AESIs), and Serious Adverse Events (SAEs), concomitant medication use, suicidal ideation and behavior, and vital signs to support the package insert for MDMA-assisted psychotherapy. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
An Open-Label, Phase 2, Multicenter, Feasibility Study of Manualized MDMA-Assisted Psychotherapy with an optional fMRI sub-study Assessing Changes in Brain Activity in Subjects with Posttraumatic Stress Disorder.
This sub-study to the MP18 protocol “An Open-Label, Multi-Site Phase 2 Study of the Safety and Effectiveness of Manualized MDMA-Assisted Psychotherapy for the Treatment of Severe Posttraumatic Stress Disorder" allows participants to participate in pre/post treatment imaging at participating investigational study sites. Study site and participants will follow all protocol procedures described in the main protocol, with the addition of imaging visits as described below.
Implementation of sub-study All eligibility criteria from the main study protocol will apply, except for the following inclusion criteria: • Absence of Traumatic Brain Injury • Absence of metal in the head • PTSD must be of non-dissociative sub-type • Absence of claustrophobia
Sub-Study Objectives & Evaluation The primary objective of this sub-study will be to explore possible biological correlates of treatment outcomes obtained from MDMA-assisted psychotherapy among participants with PTSD. • To investigate pre-post effects of MDMA-assisted psychotherapy on brain function and connectivity as measured by functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS), including response to trauma-unrelated emotional stimuli (emotional faces), response to trauma symptom provocation (personal trauma narrative). The outcome variables will be compared between timepoints (Baseline scan and post-treatment scan). • To examine the relationship between fMRI outcome variables and the primary outcome variable, namely change in CAPS-5 Total Severity Score from Baseline to 14 weeks post Baseline • The outcome variables of MRS, namely glutamate and NAA concentration levels, will be assessed at specific voxels located in the fear circuitry system, including the amygdala and the prefrontal cortex. The outcome variables will be compared between time points (Baseline scan and post-treatment). |
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E.3 | Principal inclusion criteria |
- Are at least 18 years old - Are fluent in speaking and reading the predominantly used or recognized language of the study site - Are able to swallow pills - Agree to have study visits video-recorded, including Experimental Sessions, Independent Rater assessments, and non-drug psychotherapy sessions - Must provide a contact (relative, spouse, close friend or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable - Must agree to inform the investigators within 48 hours of any medical treatments and procedures - Women of childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile), must have a highly sensitive negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate birth control through 10 days after the last Experimental Session. Adequate birth control methods include intrauterine device (IUD), injected or implanted hormonal methods, abstinence, oral hormones plus a barrier contraception, vasectomized sole partner. Not of childbearing potential is defined as permanent sterilization or assigned male at birth. - Agree to the following lifestyle modifications: comply with requirements for fasting and refraining from certain medications prior to Experimental Sessions, not participate in any other interventional clinical trials during the duration of the study, remain overnight at the study site after each Experimental Session and be driven home after, and commit to medication dosing, therapy, and study procedures. - At Screening, meet DSM-5 criteria for current PTSD - May have well-controlled hypertension that has been successfully treated with anti-hypertensive medicines, if they pass additional screening to rule out underlying cardiovascular disease - May have asymptomatic Hepatitis C virus (HCV) that has previously undergone evaluation and treatment as needed |
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E.4 | Principal exclusion criteria |
- Are not able to give adequate informed consent - Have any current problem which, in the opinion of the investigator or Medical Monitor, might interfere with participation - Would present a serious risk to others as established through clinical interview and contact with treating psychiatrist - Require ongoing concomitant therapy with a psychiatric medication with exceptions described in Section 11.0: Concomitant Medications. - Weigh less than 48 kilograms (kg) - Are pregnant or nursing or are of childbearing potential and are not practicing an effective means of birth control. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to evaluate the effectiveness of MDMA-assisted psychotherapy for treatment of PTSD, as measured by the estimand of change in CAPS-5 Total Severity Score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary objective is to evaluate the effectiveness of MDMA-assisted psychotherapy for PTSD in clinician-rated functional impairment, as measured by the mean change in Sheehan Disability Scale (SDS) item scores. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 14 |
E.8.9.2 | In all countries concerned by the trial days | 0 |