ABX-002-2001 for Depression

Recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Autobahn Therapeutics, Inc.

Must be taking: SSRIs, SNRIs

Must not be taking: Psychedelics, MAOIs, TCAs, others

Disqualifiers: Schizophrenia, Bipolar, Epilepsy, others

Prior Safety Data This treatment has passed at least one previous human trial

4 SuperSites 4 of this trial's clinics are recognized for rapid followup

4 Power Preferred Clinics 4 of this trial's clinics are considered top 20 on Power

Compensation: Varies, Up to $150

Number of Visits: 8-9

Duration: Up to 3 months

230 Participants Needed

Trial Summary

What is the purpose of this trial?

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 (approximately 35 days)  2. Treatment period (42 days)  3. Follow-up (2 weeks post treatment)

How does the drug ABX-002 for depression differ from other treatments?

While there is significant evidence that shows that thyroid hormones can improve symptoms of major depressive disorder, widespread usage has been limited due to side effects. ABX-002 is believed to more selectively activate the same receptors in the brain as thyroid hormones, meaning it aims to achieve the benefits of thyroid hormone treatments with fewer side effects.

What data supports the effectiveness of the drug ABX-002 for depression?

ABX-002 is a thyromimetic, a type of drug that mimics the effects of thyroid hormones in the body. Thyroid hormones help regulate many of the body's functions and play a role in increasing the levels of serotonin in the brain. ABX-002 is believed to target certain receptors in the brain and may help boost the effect of your current depression medication. In a previous study, ABX-002 was generally well tolerated when taken by healthy volunteers. ^{1 2 3 4 5}

Will I have to stop taking my current medications?

You will need to continue taking your current antidepressant medication as it is part of the study. However, you cannot use other medications like certain augmentation agents, biotin, or drugs affecting liver enzymes during the trial.

Eligibility Criteria

Adults with moderate to severe major depressive disorder who haven't had enough improvement from their current antidepressant can join this study. They must pass a screening and be okay with being randomly assigned to receive either ABX-002 or a placebo.

Inclusion Criteria

Are you currently taking a medication for depression but not getting the results you hoped for?

Are you willing to abstain from using marijuana (incl. vaping or edibles) for at least 3 months?

Exclusion Criteria

Have you felt depressed for more than a year and a half?

Have you been diagnosed with Schizophrenia?

Have you been diagnosed with Borderline Personality Disorder?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Approximately 5 weeks

Treatment

Participants receive ABX-002 or placebo in addition to their stable dose of SSRI/SNRI antidepressants

6 weeks

Regular visits for assessments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• ABX-002

Trial Overview The AMPLIFY trial is testing if adding ABX-002 to standard antidepressants helps improve symptoms in those not responding well to treatment. Participants will be blindly given either ABX-002 or a fake drug (placebo) for comparison over six weeks, followed by safety checks.

Participant Groups

Group I: ABX-002 + SSRI/SNRI Experimental Treatment 1 Intervention

Patients continue to receive their selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study in addition to ABX-002.

Group II: Placebo + SSRI/SNRI Placebo Group 1 Intervention

Patients continue to receive their selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study in addition to the Placebo.

Who Is Running the Clinical Trial?

Autobahn Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

310+

Findings from Research

High-dose thyroid hormone therapy (specifically levothyroxine or LT4) may help improve symptoms of depression and bipolar disorder in people who haven’t responded well to standard treatments—even if their thyroid levels are normal.

The treatment was generally well tolerated. Some people needed higher doses than those used for thyroid disease, but studies found no major long-term risks to bone or heart health, suggesting it could be a safe add-on option for treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of thyroid hormone therapy in depressive disorders Michael Bauer, Peter C. Whybrow[2021]

In a study of 50 patients, those who took low-dose T3 (a thyroid hormone) alongside their antidepressant showed faster improvement in mood in the first few weeks compared to those on antidepressants alone.

T3 was generally well tolerated, with no major side effects reported. Patients taking the placebo reported some symptoms like nervousness and fatigue more often than those who took T3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot effectiveness study: placebo-controlled trial of adjunctive L-triiodothyronine (T3) used to accelerate and potentiate the antidepressant response Michael Posternak, Scott Novak, Robert Stern, et al.[2008]

In a small exploratory study, high-dose thyroid hormone (L-T4) was associated with mood improvement in women with treatment-resistant bipolar depression. Most participants taking L-T4 alongside their usual medications experienced better mood, with very few side effects—suggesting a potential benefit worth further exploration.

Brain scans showed reduced activity in regions like the amygdala, hippocampus, and thalamus—areas commonly overactive in mood disorders—pointing to a possible brain-based mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supraphysiological doses of levothyroxine alter regional cerebral metabolism and improve mood in bipolar depression Michael Bauer, E D London, N Rasgon, et al.[2005]

New research highlights the potential of targeting the 5-HT2A serotonin receptor to help treat depression—both by blocking (antagonists) and activating (agonists) the receptor.

Researchers are designing new compounds that may deliver antidepressant effects by targeting this receptor without unwanted side effects. These early-stage studies aim to identify compounds that improve brain signaling and emotional regulation in a more targeted and potentially longer-lasting way than current medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming Depression with 5-HT2A Receptor Ligands Agata Zięba, Piotr Stępnicki, Dariusz Matosiuk, et al.[2021]

Thyroid hormones play a key role in how the body produces and uses energy by acting directly in mitochondria—the “powerhouses” of our cells.

Understanding these effects could lead to new ways to improve energy metabolism in conditions like thyroid disorders, obesity, and aging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioenergetic Aspects of Mitochondrial Actions of Thyroid Hormones Marek Kowalski, Anna M. Nowak, Katarzyna Wójcik, et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Role of thyroid hormone therapy in depressive disorders [2021]

2. United States pubmed.ncbi.nlm.nih.gov

A pilot effectiveness study: placebo-controlled trial of adjunctive L-triiodothyronine (T3) used to accelerate and potentiate the antidepressant response [2008]

3. United States pubmed.ncbi.nlm.nih.gov

Supraphysiological doses of levothyroxine alter regional cerebral metabolism and improve mood in bipolar depression [2005]

4. United States pubmed.ncbi.nlm.nih.gov

Overcoming Depression with 5-HT2A Receptor Ligands [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Bioenergetic Aspects of Mitochondrial Actions of Thyroid Hormones [2022]