A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD (MAPP2)

• ClinicalTrials.gov Identifier: NCT04077437
• Recruitment Status: Completed
• First Posted: September 4, 2019
• Results First Posted: October 11, 2023
• Last Update Posted: January 24, 2024
• Sponsor: Lykos Therapeutics
• Information provided by (Responsible Party): Lykos Therapeutics

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Posttraumatic Stress Disorder
• Interventions: Behavioral: Therapy; Drug: Midomafetamine; Drug: Placebo
• Enrollment: 121

Participant Flow

Recruitment Details	Participants were recruited through print and internet advertisements, referrals from other treatment providers, and by word of mouth.
Pre-assignment Details

Arm/Group Title	Experimental: MDMA-assisted Psychotherapy	Placebo Comparator: Placebo With Psychotherapy
Arm/Group Description	Administration of 80 to 120 mg MDMA in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. MDMA: Administration of 80 to 120 mg MDMA during three sessions of MDMA-assisted psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively.	Administration of inactive placebo in combination with psychotherapy. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. Placebo: Administration of placebo during three sessions of MDMA-assisted psychotherapy.
Period Title: Overall Study
Started	53	51
Completed [1]	52	45
Not Completed	1	6
[1] Primary Outcome (Visit 19)

Baseline Characteristics

Arm/Group Title		Experimental: MDMA-assisted Psychotherapy	Placebo Comparator: Placebo With Psychotherapy	Total
Arm/Group Description		Administration of 80 to 120 mg MDMA in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. MDMA: Administration of 80 to 120 mg MDMA during three sessions of MDMA-assisted psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively.	Administration of inactive placebo in combination with psychotherapy. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. Placebo: Administration of placebo during three sessions of MDMA-assisted psychotherapy.	Total of all reporting groups
Overall Number of Baseline Participants		53	51	104
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	53 participants	51 participants	104 participants
		38.2 (11.0)	39.9 (9.6)	39.1 (10.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	53 participants	51 participants	104 participants
	Female	32 60.4%	42 82.4%	74 71.2%
	Male	21 39.6%	9 17.6%	30 28.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	53 participants	51 participants	104 participants
	Hispanic or Latino	17 32.1%	11 21.6%	28 26.9%
	Not Hispanic or Latino	36 67.9%	39 76.5%	75 72.1%
	Unknown or Not Reported	0 0.0%	1 2.0%	1 1.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	53 participants	51 participants	104 participants
	American Indian or Alaska Native	0 0.0%	2 3.9%	2 1.9%
	Asian	5 9.4%	6 11.8%	11 10.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%	1 2.0%	1 1.0%
	Black or African American	5 9.4%	3 5.9%	8 7.7%
	White	37 69.8%	32 62.7%	69 66.3%
	More than one race	6 11.3%	7 13.7%	13 12.5%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Baseline PTSD Duration; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	53 participants	51 participants	104 participants
		16.3 (14.3)	16.1 (12.4)	16.2 (13.3)
Baseline CAPS-5 Dissociative Subtype; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	53 participants	51 participants	104 participants
		13 24.5%	11 21.6%	24 23.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Primary Endpoint in Clinician Administered PTSD Scale for DSM-V (CAPS-5)
Description	The Clinician-Administered PTSD Scale for DSM-V (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.
Time Frame	Baseline to 18 weeks post baseline post enrollment confirmation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental: MDMA-assisted Psychotherapy	Placebo Comparator: Placebo With Psychotherapy
Arm/Group Description:	Administration of 80 to 120 mg MDMA in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. MDMA: Administration of 80 to 120 mg MDMA during three sessions of MDMA-assisted psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively.	Administration of inactive placebo in combination with psychotherapy. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. Placebo: Administration of placebo during three sessions of MDMA-assisted psychotherapy.
Overall Number of Participants Analyzed	52	42
Mean (Standard Deviation); Unit of Measure: score on a scale
	-23.5 (12.1)	-15.4 (12.3)

2. Secondary Outcome

Title	Change From Baseline to Primary Endpoint in Adapted Sheehan Disability Scale (SDS) Total Score
Description	The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment that was adapted for the purposes of this study to limit missing item-level data as per the FDA requirements and included use of the three-item mean as the total score and imputation of work-related impairment. The SDS is a 3-item scale measuring the severity of disability in the domains of work, family life/home responsibilities and social/leisure activities, with each item scored on a ten-point Likert scale from 0 ('not at all impaired') to 10 ('very severely impaired'). The SDS total score was the mean of the 3 item responses. The SDS total score ranged from 0 to 10, with higher scores indicating greater functional impairment.
Time Frame	Baseline to 18 weeks post enrollment confirmation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental: MDMA-assisted Psychotherapy	Placebo Comparator: Placebo
Arm/Group Description:	Administration of 80 to 120 mg MDMA in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. MDMA: Administration of 80 to 120 mg MDMA during three sessions of MDMA-assisted psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively.	Administration of inactive placebo in combination with psychotherapy. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. Placebo: Administration of placebo during three sessions of MDMA-assisted psychotherapy.
Overall Number of Participants Analyzed	52	42
Mean (Standard Deviation); Unit of Measure: score on a scale
	-3.3 (2.6)	-2.2 (2.9)

Adverse Events

Time Frame	During the Treatment Period from the first Experimental Session to the last Integrative Session (approximately 12 weeks)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Experimental: MDMA-assisted Psychotherapy	Placebo Comparator: Placebo With Psychotherapy
Arm/Group Description	Administration of 80 to 120 mg MDMA in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. MDMA: Administration of 80 to 120 mg MDMA during three sessions of MDMA-assisted psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively.	Administration of inactive placebo in combination with psychotherapy. Behavioral: Psychotherapy: Standardized non-directive psychotherapy performed by therapist team. Placebo: Administration of placebo during three sessions of MDMA-assisted psychotherapy.
All-Cause Mortality
	Experimental: MDMA-assisted Psychotherapy	Placebo Comparator: Placebo With Psychotherapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/53 (0.00%)	0/51 (0.00%)
Serious Adverse Events
	Experimental: MDMA-assisted Psychotherapy	Placebo Comparator: Placebo With Psychotherapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/53 (0.00%)	0/51 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Experimental: MDMA-assisted Psychotherapy	Placebo Comparator: Placebo With Psychotherapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	53/53 (100.00%)	49/51 (96.08%)
Cardiac disorders
Palpitations †	5/53 (9.43%)	1/51 (1.96%)
Eye disorders
Vision blurred †	8/53 (15.09%)	0/51 (0.00%)
Mydriasis †	6/53 (11.32%)	0/51 (0.00%)
Visual impairment †	3/53 (5.66%)	0/51 (0.00%)
Gastrointestinal disorders
Nausea †	24/53 (45.28%)	11/51 (21.57%)
Dry mouth †	9/53 (16.98%)	4/51 (7.84%)
Abdominal discomfort †	3/53 (5.66%)	3/51 (5.88%)
Abdominal pain upper †	5/53 (9.43%)	1/51 (1.96%)
Vomiting †	4/53 (7.55%)	2/51 (3.92%)
Abdominal pain †	2/53 (3.77%)	3/51 (5.88%)
Diarrhoea †	1/53 (1.89%)	3/51 (5.88%)
General disorders
Fatigue †	14/53 (26.42%)	9/51 (17.65%)
Feeling hot †	14/53 (26.42%)	6/51 (11.76%)
Feeling cold †	11/53 (20.75%)	3/51 (5.88%)
Chest discomfort †	9/53 (16.98%)	2/51 (3.92%)
Chills †	8/53 (15.09%)	1/51 (1.96%)
Feeling jittery †	8/53 (15.09%)	0/51 (0.00%)
Feeling abnormal †	5/53 (9.43%)	2/51 (3.92%)
Feeling of body temperature change †	5/53 (9.43%)	0/51 (0.00%)
Thirst †	4/53 (7.55%)	1/51 (1.96%)
Gait disturbance †	3/53 (5.66%)	0/51 (0.00%)
Infections and infestations
COVID-19 †	4/53 (7.55%)	4/51 (7.84%)
Upper respiratory tract infection †	3/53 (5.66%)	3/51 (5.88%)
Investigations
Heart rate increased †	3/53 (5.66%)	0/51 (0.00%)
Metabolism and nutrition disorders
Decreased appetite †	19/53 (35.85%)	5/51 (9.80%)
Musculoskeletal and connective tissue disorders
Muscle tightness †	31/53 (58.49%)	13/51 (25.49%)
Myalgia †	7/53 (13.21%)	4/51 (7.84%)
Neck pain †	3/53 (5.66%)	7/51 (13.73%)
Pain in jaw †	6/53 (11.32%)	4/51 (7.84%)
Arthralgia †	4/53 (7.55%)	5/51 (9.80%)
Back pain †	3/53 (5.66%)	3/51 (5.88%)
Muscle spasms †	4/53 (7.55%)	0/51 (0.00%)
Nervous system disorders
Headache †	38/53 (71.70%)	31/51 (60.78%)
Dizziness †	15/53 (28.30%)	8/51 (15.69%)
Paraesthesia †	10/53 (18.87%)	1/51 (1.96%)
Nystagmus †	7/53 (13.21%)	1/51 (1.96%)
Disturbance in attention †	3/53 (5.66%)	3/51 (5.88%)
Hypoaesthesia †	5/53 (9.43%)	1/51 (1.96%)
Tremor †	6/53 (11.32%)	0/51 (0.00%)
Psychiatric disorders
Suicidal ideation †	18/53 (33.96%)	21/51 (41.18%)
Insomnia †	19/53 (35.85%)	15/51 (29.41%)
Anxiety †	15/53 (28.30%)	12/51 (23.53%)
Depressed mood †	5/53 (9.43%)	6/51 (11.76%)
Restlesness †	8/53 (15.09%)	2/51 (3.92%)
Bruxism †	7/53 (13.21%)	1/51 (1.96%)
Nightmare †	4/53 (7.55%)	3/51 (5.88%)
Emotional disorder †	3/53 (5.66%)	2/51 (3.92%)
Irritability †	3/53 (5.66%)	2/51 (3.92%)
Panic attack †	3/53 (5.66%)	1/51 (1.96%)
Binge eating †	0/53 (0.00%)	3/51 (5.88%)
Dissociation †	3/53 (5.66%)	0/51 (0.00%)
Skin and subcutaneous tissue disorders
Hyperhidrosis †	18/53 (33.96%)	3/51 (5.88%)
Vascular disorders
Flushing †	3/53 (5.66%)	1/51 (1.96%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Berra Yazar-Klosinski / Chief Scientific Officer
• Organization: MAPS Public Benefit Corporation (MAPS PBC)
• Phone: (831) 429-6362
• EMail: trialdata@mapsbcorp.com

Publications:

Leon AC, Olfson M, Portera L, Farber L, Sheehan DV. Assessing psychiatric impairment in primary care with the Sheehan Disability Scale. Int J Psychiatry Med. 1997;27(2):93-105. doi: 10.2190/T8EM-C8YH-373N-1UWD.

Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, Keane TM. The development of a Clinician-Administered PTSD Scale. J Trauma Stress. 1995 Jan;8(1):75-90. doi: 10.1007/BF02105408.

• Responsible Party: Lykos Therapeutics
• ClinicalTrials.gov Identifier: NCT04077437
• Other Study ID Numbers: MAPP2
• First Submitted: August 30, 2019
• First Posted: September 4, 2019
• Results First Submitted: September 19, 2023
• Results First Posted: October 11, 2023
• Last Update Posted: January 24, 2024