Generalized Anxiety Disorder
Conditions
Brief summary
A Phase 3, Double-blind, Placebo-controlled Study (Part A) with an Open-label Extension (Part B) Evaluating DT120 Compared to Placebo in Generalized Anxiety Disorder - Panorama
Detailed description
The study will enroll up to 375 participants aged 18 to 74 years, inclusive with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) confirmed primary diagnosis of GAD and a minimum HAM A total score of at least 20 at Screening and Baseline without clinically relevant medical or psychiatric history. The study consists of a 12-week randomized, double-blind, single-dose administration period evaluating DT120 versus placebo, followed by a 40-week extension phase with the opportunity for open-label treatment. During this phase, participants will be monitored and evaluated for potential treatment with DT120 based on pre-specified safety and symptom severity criteria.
Interventions
OTHERPlacebo
A substance that is designed to have no therapeutic value
DRUGDT120
A psychoactive substance that mediates effects mainly through an agonist activity in the serotonin 2A receptor (5-HT2A)
Sponsors
Definium Therapeutics US, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of GAD per DSM-5 2. Male or female aged 18 to 74 3. HAM-A Total Score ≥20
Exclusion criteria
1. Certain psychiatric disorders (other than generalized anxiety disorder) 2. First degree relative with or lifetime history of a psychotic disorder or bipolar disorder 3. Current diagnosis of alcohol or substance use disorder (excluding nicotine and caffeine) 4. Any clinically significant unstable illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Hamilton Anxiety Rating Scale (HAM-A) total score at Week 12 | Baseline to Week 12 | The HAM-A consists of the following 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HAM-A response (reduction from Baseline score of ≥50%) at each timepoint assessed during the 12-week double-blind period | Baseline to Week 12 | The HAM-A consists of the following 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. |
| HAM-A remission (total score ≤7) at each timepoint assessed during the 12-week double-blind treatment period | Baseline to Week 12 | The HAM-A consists of the following 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. |
| Clinical Global Impression - Improvement (CGI-I) Scale score at each timepoint assessed during the 12-week double-blind period | Day 2 to Week 12 | The CGI-I scale is used to measure the clinician's assessment of how much the participant's illness has improved or worsened relative to Baseline (Visit 2). The CGI-I comprises one item with 7 possible ratings (1-7 points), where a lower score indicates improvement, and a higher score indicates worsening. |
| Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in Clinical Global Impression - Severity (CGI-S) Scale score | Baseline to Week 12 | The CGI-S scale assesses the clinician's impression of the participant's current severity of illness relative to the clinician's experience with patients who have the same diagnosis. The CGI-S comprises one item with 7 possible ratings (1-7 points), where a higher score indicates more severe illness. |
| Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in Patient Global Impression - Severity (PGI-S) Scale score | Baseline to Week 12 | The PGI scale is the patient-reported outcome (PRO) counterpart to the CGI scale. The PGI-S comprises one participant-completed item with 5 possible ratings (1-5) where a higher score indicates more severe illness. |
| Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in - Montgomery-Åsberg Depression Rating Scale (MADRS) total score | Baseline to Week 12 | The MADRS is used to assess depression severity and to detect changes due to antidepressant treatment. The MADRS includes 10 clinician-completed items. Each of the 10 questions is scored with a range of 0-6 points. An item score of 0 indicates item not present or normal, while an item score of 6 indicates severe or continuous presence of the symptoms. The total possible score is 60, and higher scores represent a more severe condition. |
| Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in - Work Productivity and Activity Impairment Specific Health Problem Questionnaire (WPAI-SHP) | Baseline to Week 12 | The WPAI-SHP is a 6-item questionnaire, with a recall period of the past 7 days. The WPAI measures impairments in both paid work and unpaid work. It measures absenteeism, presenteeism as well as impairment in unpaid activity because of the health problem under study. |
| Change from Baseline throughout the 12-week double-blind period at each timepoint assessed in - EuroQol-5 Dimensions - 5 Levels (EQ-5D-5L) | Baseline to Week 12 | The EuroQol 5 Dimension 5 Level (EQ-5D-5L) is a self-reported outcome measure used to evaluate health outcomes over a wide range of health conditions and treatments. The EQ-5D consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). |
| Change from Baseline in the Changes in Sexual Functioning Questionnaire (CSFQ-14) total score at each timepoint assessed during the double-blind period | Baseline to Week 12 | The CSFQ-14 is a structured self-reported questionnaire designed to measure illness- and medication-related changes in sexual functioning that consists of 14 items measuring sexual functioning as a total score (14 items). There is a male and female version of the CSFQ-14 scale and a total score of less than 47 for men and less than 41 for women indicates sexual dysfunction. Lower scores are associated with worsened sexual functioning. |
| Percent of men and women with normal and abnormal sexual functioning at each timepoint assessed during the double-blind period | Baseline to Week 12 | The CSFQ-14 is a structured self-reported questionnaire designed to measure illness- and medication-related changes in sexual functioning that consists of 14 items measuring sexual functioning as a total score (14 items). There is a male and female version of the CSFQ-14 scale and a total score of less than 47 for men and less than 41 for women indicates sexual dysfunction. Lower scores are associated with worsened sexual functioning. |
| Percent of participants requiring one, two, three, four, or five doses of DT120 during the 52-week study (Part A and Part B) as assessed by participants meeting protocol-specified retreatment criteria during the 40-week open-label period | Day 1 to Week 52 | Percent of participants requiring one, two, three, four, or five doses of DT120 during the 52-week study (Part A and Part B) as assessed by participants meeting protocol-specified retreatment criteria during the 40-week open-label period |
| Time to first treatment or lack of efficacy in the open-label period (Part B) | Day 1 to Week 52 | Measured as time from first dosing in the Double-blind period to participant meeting HAM-A criteria for re-dose or meeting criteria for lack of efficacy |
| Need for DT120 treatment as assessed by the average number of DT120 treatments during the study | Day 1 to Week 52 | Average number of treatments assessed from first dose in the double-blind period through completion of the open label extension. |
| HAM-A response (reduction from Baseline score of ≥50%) at each timepoint assessed during the 40-week open-label period | 40 week open label period | The HAM-A consists of the following 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. |
| HAM-A remission (total score ≤7) at each timepoint assessed during the 40-week open-label period | 40 week open label period | The HAM-A consists of the following 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. |
| Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in Clinical Global Impression - Severity (CGI-S) Scale score | Baseline to Week 52 | The CGI-S scale assesses the clinician's impression of the participant's current severity of illness relative to the clinician's experience with patients who have the same diagnosis. The CGI-S comprises one item with 7 possible ratings (1-7 points), where a higher score indicates more severe illness. |
| Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in Patient Global Impression - Severity (PGI-S) Scale score | Baseline to Week 52 | The PGI scale is the patient-reported outcome (PRO) counterpart to the CGI scale. The PGI-S comprises one participant-completed item with 5 possible ratings (1-5) where a higher score indicates more severe illness. |
| Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in MADRS total score | Baseline to Week 52 | The MADRS is used to assess depression severity and to detect changes due to antidepressant treatment. The MADRS includes 10 clinician-completed items. Each of the 10 questions is scored with a range of 0-6 points. An item score of 0 indicates item not present or normal, while an item score of 6 indicates severe or continuous presence of the symptoms. The total possible score is 60, and higher scores represent a more severe condition. |
| Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in WPAI-SHP | Baseline to Week 52 | The WPAI-SHP is a 6-item questionnaire, with a recall period of the past 7 days. The WPAI measures impairments in both paid work and unpaid work. It measures absenteeism, presenteeism as well as impairment in unpaid activity because of the health problem under study. |
| Change from Double-blind Baseline throughout the 40-week open-label period at each timepoint assessed in EQ-5D-5L | Baseline to Week 52 | The EuroQol 5 Dimension 5 Level (EQ-5D-5L) is a self-reported outcome measure used to evaluate health outcomes over a wide range of health conditions and treatments. The EQ-5D consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). |
| CSFQ-14 total score at each timepoint assessed during the open-label period | 40 week open label period | The CSFQ-14 is a structured self-reported questionnaire designed to measure illness- and medication-related changes in sexual functioning that consists of 14 items measuring sexual functioning as a total score (14 items). There is a male and female version of the CSFQ-14 scale and a total score of less than 47 for men and less than 41 for women indicates sexual dysfunction. Lower scores are associated with worsened sexual functioning. |
| Change from Baseline in HAM-A total score at Week 8, Week 4, Week 2, and Week 1 | Week 8, Week 4, Week 2, and Week 1 | The HAM-A consists of the following 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. |
| Percent men and women with normal and abnormal sexual functioning at each timepoint assessed during the open-label period | 40 week open label period | The CSFQ-14 is a structured self-reported questionnaire designed to measure illness- and medication-related changes in sexual functioning that consists of 14 items measuring sexual functioning as a total score (14 items). There is a male and female version of the CSFQ-14 scale and a total score of less than 47 for men and less than 41 for women indicates sexual dysfunction. Lower scores are associated with worsened sexual functioning. |
Countries
Czechia, France, Germany, Poland, United Kingdom, United States
Outcome results
None listed