Clinical trial NCT06633016: Study of ABX-002 for the Adjunctive Treatment of Major Depressive Disorder (AMPLIFY)
Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ABX-002 for the Adjunctive Treatment of Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Major Depressive Disorder
Lead sponsor: Autobahn Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-10-09
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if ABX-002 added to an existing antidepressant treatment will benefit depression symptoms in adults with moderate to severe major depressive disorder who have had an inadequate response to their antidepressant.

This is a double-blind, placebo-controlled, 2-arm, parallel-group, Phase 2 study, randomized 1:1 (ABX-002: placebo).

The study will include the following stages:

1. Screening, Treatment, and Follow-Up ; approximately 35 days
2. 42-day Treatment Period
3. 2-week post dose Safety Follow-up Period


Eligibility criteria: Inclusion Criteria:

* Meets the DSM-5 criteria for Major Depressive Disorder, with a current major depressive episode duration of \> 6 weeks and no longer than 12 months.
* A score of ≤ 22 (midrange mild/moderate) on the Hamilton Anxiety Rating Scale.
* Montgomery-Asberg Depression Rating Scale total score \[indicating moderate to severe depression\] at Screening and at Baseline.
* Subject is compliantly using a single selective serotonin reuptake inhibitors / serotonin norepinephrine reuptake inhibitor antidepressant for at least 6 weeks but not more than 12 months for their current episode of depression, with an adequate dose, and with an inadequate response as defined by the Antidepressant Treatment Response Questionnaire. The dosage of the current antidepressant must have been stable for the past 4 weeks, and the dosage and specific antidepressant used should remain the same from Screening through the end of the Follow-up Period.

Exclusion Criteria:

Note: History implies lifetime history, unless otherwise specified

* History of schizophrenia or other psychotic disorder, major depressive disorder with psychotic features or concomitant DSM-5 depressive disorders, bipolar I or II disorder, cyclothymic disorder, delirium, dementia, amnestic disorder, or cognitive disorder.
* History of obsessive-compulsive disorder, posttraumatic stress disorder, panic disorder, or eating disorder, according to DSM-5 criteria.
* Primary diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder, according to DSM-5 criteria. History of self-injurious behavior is exclusionary.
* Has failed more than 2 single selective serotonin reuptake inhibitors / serotonin norepinephrine reuptake inhibitor antidepressant treatments, including the current serotonin reuptake inhibitors / serotonin norepinephrine reuptake inhibitor, during the current depressive episode, despite an adequate dose (per Antidepressant Treatment Response Questionnaire) and duration (at least 6 weeks).
* Failure to respond to triiodothyronine or thyroxine augmentation for the treatment of depression.
* Started new psychotherapy or had a change in the intensity of psychotherapy within 8 weeks before Screening.
* Is suicidal at Screening or Baseline
* History or current evidence within previous 3 months before Screening of uncontrolled, clinically significant neurological, gastrointestinal, respiratory, renal, hepatic, immunological, hematological, or other medical disorder, including cancer, that would jeopardize the safe participation of the subject in the study (in the opinion of the Investigator).
* History of thyroid disease
* History of cardiovascular disease
* History of multiple endocrine neoplasia syndrome
* Diagnosis of epilepsy or history of convulsions, including childhood febrile seizure. Use of co-administered drugs that may lower seizure threshold is excluded.
* Females who are pregnant, intend to become pregnant within 90 days of the last dose of study drug, or are breastfeeding.
* Antidepressants: Prior use of psychedelics, ketamine, or esketamine, for the treatment of Major Depressive Disorder.
* Antidepressants: Current use, or use within 4 weeks prior to Screening, of any other augmentation agents for Major Depressive Disorder (e.g. second-generation antipsychotics \[SGA\], monoamine oxidase inhibitors \[MAOI\], tricyclic antidepressants \[TCA\], lithium, or bupropion)
* Current or prior use of treatment for hypothyroidism including but not limited to synthetic or natural thyroid hormone, triiodothyronine and/or thyroxine.
* Concomitant use of biotin of any dose and in any preparation 7 days prior to Day 1 until after the last study visit at Week 8 (Day 56).
* Medications that are strong cytochrome P450 3A4 inhibitors or strong cytochrome P450 3A4 inducers are not allowed.
* Prescription drug/controlled substance abuse, or illicit substance use within 1 year of Screening or positive urine drug results at Screening or Baseline for an illicit substance.

Primary outcomes:
measure: Change from Baseline in the 17-item Hamilton Rating Scale for Depression (HAMD-17)
timeFrame: 6 weeks
Secondary outcomes:
measure: Change from Baseline for Clinical Global Impression of Severity (CGI-S)
timeFrame: 6 weeks
measure: Change from Baseline for Sheehan Disability Scale (SDS)
timeFrame: 6 weeks
measure: Change from baseline for 6-item Hamilton Rating Scale for Depression (HAMD-6)
timeFrame: 6 weeks
measure: Change from baseline for 17-item Hamilton Rating Scale for Depression (HAMD-17)
timeFrame: 6 weeks
measure: Change from baseline for 29-item Hamilton Rating Scale for Depression (HAMD-29)
timeFrame: 6 weeks
measure: Patient Global Impression-Improvement (PGI-I)
timeFrame: 6 weeks
measure: Assessment of safety and tolerability of ABX-002 compared with placebo using adverse events
timeFrame: 6 weeks
measure: Assessment of safety and tolerability of ABX-002 compared with placebo using physical evaluations
timeFrame: 6 weeks
measure: Assessment of safety and tolerability of ABX-002 compared with placebo using standard laboratory safety tests
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Autobahn Site #131
state: Alabama
city: Chandler
country: United States
facility: Autobahn Site #132
state: Arizona
city: Phoenix
country: United States
facility: Autobahn Site #116
state: Arizona
city: Tucson
country: United States
facility: Autobahn Site #136
state: Arizona
city: Encino
country: United States
facility: Autobahn Site #113
state: California
city: Encino
country: United States
facility: Autobahn Site #133
state: California
city: Glendale
country: United States
facility: Autobahn Site #124
state: California
city: Long Beach
country: United States
facility: Autobahn Site #140
state: California
city: Los Alamitos
country: United States
facility: Autobahn Site #121
state: California
city: Newport Beach
country: United States
facility: Autobahn Site #117
state: California
city: Oceanside
country: United States
facility: Autobahn Site #106
state: California
city: San Jose
country: United States
facility: Autobahn Site #119
state: California
city: Walnut Creek
country: United States
facility: Autobahn Site #126
state: California
city: Cromwell
country: United States
facility: Autobahn Site #122
state: Connecticut
city: Brandon
country: United States
facility: Autobahn Site #108
state: Florida
city: Hialeah
country: United States
facility: Autobahn Site #110
state: Florida
city: Jacksonville
country: United States
facility: Autobahn Site #101
state: Florida
city: Lake City
country: United States
facility: Autobahn Site #139
state: Florida
city: Miami
country: United States
facility: Autobahn Site #111
state: Florida
city: Orlando
country: United States
facility: Autobahn Site #102
state: Florida
city: Atlanta
country: United States
facility: Autobahn Site #123
state: Georgia
city: Decatur
country: United States
facility: Autobahn Site #112
state: Georgia
city: Savannah
country: United States
facility: Autobahn Site #120
state: Georgia
city: Boston
country: United States
facility: Autobahn Site #137
state: Massachusetts
city: Watertown
country: United States
facility: Autobahn Site #138
state: Massachusetts
city: Saint Charles
country: United States
facility: Autobahn Site #127
state: Missouri
city: Las Vegas
country: United States
facility: Autobahn Site #130
state: Nevada
city: Berlin
country: United States
facility: Autobahn Site #129
state: New Jersey
city: Brooklyn
country: United States
facility: Autobahn Site #105
state: New York
city: Brooklyn
country: United States
facility: Autobahn Site #134
state: New York
city: New York
country: United States
facility: Autobahn Site #125
state: New York
city: Staten Island
country: United States
facility: Autobahn Site #104
state: New York
city: Beachwood
country: United States
facility: Autobahn Site #109
state: Ohio
city: Oklahoma City
country: United States
facility: Autobahn Site #107
state: Oklahoma
city: North Charleston
country: United States
facility: Autobahn Site #128
state: South Carolina
Study officials:
References: