Clinical Trial Results:
An Open- Label, Phase 2, Multicenter Feasibility Study of Manualized MDMA-Assisted Psychotherapy with an fMRI sub-study Assessing Changes in Brain Activity in Subjects with Posttraumatic Stress Disorder.
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Summary
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EudraCT number |
2018-001718-13 |
Trial protocol |
NL CZ NO DE GB ES |
Global end of trial date |
15 Dec 2023
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Results information
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Results version number |
v1 |
This version publication date |
05 Jan 2025
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First version publication date |
05 Jan 2025
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MP18
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04030169 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
MAPS Europe B.V.
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Sponsor organisation address |
Tine van Dethstraat 83, 2331CD, Leiden, Netherlands,
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Public contact |
Julie Blaisdell, Lykos Therapeutics, 01 877-627-7722, julie.blaisdell@lykospbc.com
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Scientific contact |
Berra Yazar-Klosinski, Lykos Therapeutics, 01 877-627-7722, berra.yazar-klosinski@lykospbc.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Dec 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Dec 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Dec 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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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 from baseline to 13 weeks post-baseline.
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Protection of trial subjects |
During Screening, throughout MDMA-assisted psychotherapy, and during assessment of study measures, participants will be asked to think about and discuss their thoughts and emotions relating to the traumatic event or events associated with their PTSD. They may experience intense emotional responses or suicidal ideation as a result of recalling and speaking about this material. The therapy team will minimize risks by carefully evaluating all participants to determine if there is a current risk of suicidal behavior. A qualified study team member will administer the C-SSRS, a validated measure for assessing suicide risk, at regular, protocol-specified intervals and as needed to monitor for the development and intensity of suicidal ideation and/or behavior. Study teams will implement a protocol-defined plan to address elevated or imminent suicide risk, including continued monitoring and assessment of risk via regular check-ins until the participant stabilizes, discontinuation of study treatment, and/or escorting the participant to the appropriate health services depending on the degree of risk as assessed by the C-SSRS.
MDMA is known to transiently increase heart rate and blood pressure in a dose-dependent manner that is generally not problematic for physically healthy individuals. Before and after drug administration in Experimental Sessions, the study teams monitor vital signs. Should the participant experience signs or symptoms indicative of a cardiac event, the study physician will be contacted immediately and the participant will be taken to emergency services. Pending transport to the hospital the site team may take any measures ordered by the site physician including administering medication such as aspirin or nitroglycerin or providing supplemental oxygen per local standards.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
02 Apr 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 8
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Country: Number of subjects enrolled |
Norway: 2
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Country: Number of subjects enrolled |
United Kingdom: 6
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Country: Number of subjects enrolled |
Czechia: 3
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Country: Number of subjects enrolled |
Germany: 2
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Worldwide total number of subjects |
21
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EEA total number of subjects |
15
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
21
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were recruited by 7 study centers in the United Kingdom, Germany, Norway, the Czech Republic, and the Netherlands through referrals from other psychiatrists, psychotherapists, or physicians, print and internet advertisements, and by word of mouth. | ||||||||||
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Pre-assignment
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Screening details |
Inclusion: Aged at least 18 years old; Able to swallow pills; current, chronic, severe PTSD; Current alcohol or substance use disorder without safety concern Exclusion: Current serious suicide risk; Any medical condition that could make receiving a sympathomimetic drug harmful (due to increase in blood pressure and heart rate) | ||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Blinding implementation details |
This was an open-label trial. Therefore, blinding implementation details are not applicable.
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Arms
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Arm title
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Open-label MDMA-assisted therapy | ||||||||||
Arm description |
Two open-label sessions of MDMA-assisted therapy, scheduled approximately 1 month apart, with an initial dose of midomafetamine (MDMA) HCl of 80 or 120 mg and optional supplemental dose half that of initial dose (40 or 60 mg) 1.5 to 2 hours later administered at each session. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Midomafetamine HCl
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Investigational medicinal product code |
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Other name |
MDMA HCl, MDMA, 3,4-methylenedioxymethamphetamine, Midomafetamine
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Midomafetamine HCl is administered at 2 experimental sessions occurring approximately one month apart. In the first Experimental Session, the initial dose is 80 mg. In the second Experimental Session, the initial dose may be increased to 120 mg unless tolerability issues emerge with the first dose or the participant declines. In each Experimental Session, 1.5 to 2 hours after the initial dose is given, the participant will be administered a supplemental half-dose (i.e. 40 mg or 60 mg, respectively) unless tolerability issues emerge with the first dose or the participant declines.
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Baseline characteristics reporting groups
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Reporting group title |
Open-label MDMA-assisted therapy
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Reporting group description |
Two open-label sessions of MDMA-assisted therapy, scheduled approximately 1 month apart, with an initial dose of midomafetamine (MDMA) HCl of 80 or 120 mg and optional supplemental dose half that of initial dose (40 or 60 mg) 1.5 to 2 hours later administered at each session. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Safety Set
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All participants exposed to study drug
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End points reporting groups
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Reporting group title |
Open-label MDMA-assisted therapy
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Reporting group description |
Two open-label sessions of MDMA-assisted therapy, scheduled approximately 1 month apart, with an initial dose of midomafetamine (MDMA) HCl of 80 or 120 mg and optional supplemental dose half that of initial dose (40 or 60 mg) 1.5 to 2 hours later administered at each session. | ||
Subject analysis set title |
Safety Set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All participants exposed to study drug
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End point title |
Change From Baseline to Visit 14 in CAPS-5 Total Severity Score [1] | ||||||||
End point description |
The CAPS-5 is a 30-item semi-structured interview assessing PTSD in the past month through diagnostic and symptom severity scores anchored to a DSM-5 defined traumatic event. The CAPS-5 produces a Total Severity Score based on severity of PTSD domains described in the DSM-5, as well as a categorical rating indicating whether a participant meets PTSD diagnostic criteria. CAPS-5 Total Symptom Severity scores range from 0 to 80 with higher values designating greater symptom severity. CAPS-5 assigns PTSD diagnosis as being present or absent.
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End point type |
Primary
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End point timeframe |
Baseline to 13 weeks post-baseline
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This is an open-label, single-arm trial. |
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| Notes [2] - Includes all participants with data available at the primary endpoint assessment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline to Visit 14 in Sheehan Disability Scale (SDS) Scores | ||||||||||||||||
End point description |
The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment for PTSD. The SDS is a 3-item scale measuring the severity of disability (i.e., the degree of impairment) in the domains of work, family life/home responsibilities and social/leisure activities. Responses are recorded using an 11-point scale (0 = not at all to 10 = extremely) and 5 verbal tags (not at all, mildly, moderately, markedly, extremely). For participants who are not able to work for reasons unrelated to PTSD, the measure includes an option to skip the work-related impairment item, and the reason was collected. The impact of missing item-level data was mitigated by averaging across the items to obtain a Total Score, rather than a straight sum.
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End point type |
Secondary
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End point timeframe |
Baseline to 13 weeks post-baseline
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| Notes [3] - Includes all participants with data available at the primary endpoint assessment. |
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| No statistical analyses for this end point | |||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Treatment emergent adverse events, defined as adverse events that occurred during the study treatment period from the first experimental session to the last integrative session.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
Open-label MDMA-assisted therapy
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Reporting group description |
Two open-label sessions of MDMA-assisted therapy, scheduled approximately 1 month apart, with an initial dose of midomafetamine (MDMA) HCl of 80 or 120 mg and optional supplemental dose half that of initial dose (40 or 60 mg) 1.5 to 2 hours later administered at each session. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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29 Mar 2021 |
Changes to the protocol incorporated in the amendment dated 29MAR2021 included:
- Removal of the dissociative subtype of PTSD from the list of exclusion criteria
- Addition of a requirement that participants not begin a new form of mental healthcare during the screening or treatment phases of the trial without consulting with the study team
- Removal of the International Personality Disorder Examination (IDPE) as a screening measure to instead use the Structured Clinical Interview for DSM-5 - Personality Disorders (SCID-PD) across all study sites
- Updates to protocol safety information to reflect current Investigator Brochure |
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22 Nov 2022 |
Changes to the protocol incorporated in the amendment dated 22NOV2022 included:
- Updates to reflect a change in IMP packaging from bulk bottles to containers with IMP for a single experimental session
- Updates to indicate that audio/video recordings from study visits would be deleted following completion of the required reviews and would not be retained for future research or educational use |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| This was an open-label, feasibility study in a small sample, limiting interpretation of the results. | |||
