RE104 for Postpartum Depression

No longer recruiting at 33 trial locations

Overseen By Jasna Hocevar-Trnka, M.D.

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Reunion Neuroscience Inc

Must be taking: SSRIs

Must not be taking: Psychotropics, Psychedelics

Disqualifiers: Bipolar, Schizophrenia, Psychosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 4

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a single dose of RE104 for Injection can reduce symptoms of postpartum depression (PPD), a condition that causes severe mood swings and anxiety after childbirth. It compares two doses of RE104 to determine which is more effective. Women who have experienced PPD starting during pregnancy or shortly after birth, and who are not currently breastfeeding, may be eligible to join. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial requires that you are either not using any psychotropic medications or psychotherapy for 30 days before screening, or you are on a stable regimen of SSRIs or psychotherapy for 30 days before screening. If you are on other medications, you may need to stop them.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that RE104 for Injection is generally safe for humans. In earlier studies, participants who took a 30 mg dose of RE104 experienced manageable side effects. The data indicates that serious negative side effects were rare or absent. These findings suggest that RE104 could be a safe option for treating postpartum depression (PPD), as previous research has demonstrated similar safety results with this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for postpartum depression?

Unlike the standard treatments for postpartum depression, which mainly include antidepressants like SSRIs, RE104 is unique because it targets the condition through a novel mechanism. RE104 works by modulating serotonin receptors in the brain, potentially offering faster relief from symptoms. Additionally, it is administered via a single subcutaneous injection, which could be more convenient and faster-acting compared to daily oral medications. Researchers are excited about RE104 because it might provide a quicker onset of action and greater convenience for new mothers struggling with postpartum depression.

What evidence suggests that RE104 for Injection might be an effective treatment for postpartum depression?

Research shows that RE104 for Injection might help lessen symptoms of postpartum depression (PPD). In one study, 71.4% of patients who received a 30 mg dose of RE104 had very low depression scores by Day 7, indicating a significant reduction in symptoms. Additionally, 77.1% of patients experienced at least a 50% improvement in their depression symptoms after just one dose. These findings suggest that RE104 can quickly and effectively reduce depressive symptoms in PPD patients. Participants in this trial will receive either a 30 mg dose or a 1.5 mg dose of RE104, with the 30 mg dose previously showing a strong and fast impact on improving mood. ^{1 2 4 6 7}

Who Is on the Research Team?

Jasna Hocevar-Trnka, M.D.

Principal Investigator

Reunion Neuroscience Inc

Are You a Good Fit for This Trial?

This trial is for individuals who are within 12 months postpartum and have moderate-to-severe depression. They must not be breastfeeding, meet specific criteria on the Hamilton Depression Scale, and either be free from psychotropic medications and psychotherapy for 30 days or on a stable regimen of SSRIs or therapy.

Inclusion Criteria

I gave birth within the last 12 months.

I have stopped breastfeeding.

My depression severity meets the required level on the HAM-D scale.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single subcutaneous injection of either 30 mg or 1.5 mg RE104 for Injection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

3 visits (in-person) on Day 7, Day 14, and Day 28

What Are the Treatments Tested in This Trial?

Interventions

• RE104 for Injection

Trial Overview The study tests whether a single dose of RE104 for Injection can reduce depressive symptoms in those with postpartum depression compared to an active-placebo. It aims to see if this new treatment is safe and effective.

How Is the Trial Designed?

Group I: 30 mg RE104 Experimental Treatment 1 Intervention

A single subcutaneous injection of 30 mg RE104 for Injection

Group II: 1.5 mg RE104 Active Control 1 Intervention

A single subcutaneous injection of 1.5 mg RE104 for Injection

Who Is Running the Clinical Trial?

Reunion Neuroscience Inc

Lead Sponsor

Trials

2

Recruited

90+

Published Research Related to This Trial

A pharmacokinetic analysis of four breastfeeding women showed that ketamine and its metabolites are present in breast milk at low levels that decline rapidly within 12 hours after administration.

The mean relative infant dose (RID) of ketamine from two different doses (0.5 mg/kg and 1.0 mg/kg) was found to be 0.650% and 0.766%, respectively, suggesting that ketamine may be used cautiously in breastfeeding women with postpartum emotional disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Pharmacokinetics of Ketamine in the Breast Milk of Lactating Women: Quantification of Ketamine and Metabolites. Wolfson, P., Cole, R., Lynch, K., et al.[2023]

Brexanolone, a synthetic neuroactive steroid, has shown rapid effectiveness in reducing depressive symptoms in postpartum depression, leading to its submission for FDA approval.

SAGE-217, an oral allopregnanolone analog, and ganaxolone, a synthetic analog being tested in various forms, also demonstrate promising results in treating severe postpartum depression, indicating a new direction in postpartum depression therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development. Frieder, A., Fersh, M., Hainline, R., et al.[2023]

In a phase 2 trial involving 21 women with severe post-partum depression, brexanolone significantly reduced depression scores compared to placebo, with a mean reduction of 21.0 points on the HAM-D scale versus 8.8 points for placebo, indicating its efficacy as a treatment.

Brexanolone was well-tolerated, with no serious adverse events reported, and only moderate side effects like dizziness and somnolence, suggesting a favorable safety profile for this new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial. Kanes, S., Colquhoun, H., Gunduz-Bruce, H., et al.[2018]

Brexanolone injection significantly reduced depression scores in women with moderate to severe post-partum depression compared to placebo, showing a clinically meaningful effect within 60 hours of treatment.

The treatment demonstrated a rapid onset of action and a durable response, although some patients experienced adverse events like headache and dizziness, indicating a need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Meltzer-Brody, S., Colquhoun, H., Riesenberg, R., et al.[2021]

Postpartum depression (PPD) is linked to lower levels of progesterone-derived neurosteroids, which help reduce anxiety and depression after childbirth.

Neurosteroid replacement therapy (NRT) using brexanolone, which modulates GABA-A receptors, shows potential as a rapid treatment for PPD, offering a different mechanism of action compared to traditional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroendocrine insights into neurosteroid therapy for postpartum depression. Reddy, DS.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06342310

RE104 Safety and Efficacy Study in Postpartum Depression The purpose of this study is to determine if treatment with a single dose of RE104 for Injection reduces depressive symptoms in participants with moderate-to- ...

2. reunionneuro.com reunionneuro.com/2025/08/18/reunion-neuroscience-announces-positive-topline-results-from-reconnect-phase-2-clinical-trial-of-re104-for-the-treatment-of-postpartum-depression-ppd/

Achieved Primary Endpoint with 30mg Dose of RE104 ... 71.4% of patients treated with RE104 30mg were in remission at Day 7, defined as a total MADRS score of ≤10, as compared to 41.0% of patients ...

3. psychiatrictimes.com psychiatrictimes.com/view/re104-a-novel-fast-acting-psychedelic-for-postpartum-depression

RE104: A Novel, Fast-Acting Psychedelic for Postpartum ... Phase 1 study showed RE104's safety and tolerability, with no serious adverse effects, supporting its use in postpartum depression treatment.

4. fiercebiotech.com fiercebiotech.com/biotech/reunions-psychedelic-prodrug-reduces-post-partum-depression-phase-2-study

Reunion's psychedelic reduces postpartum depression in ... A total of 77.1% of patients treated with a single 30-mg subcutaneous dose of RE104 saw at least a 50% improvement in a depression score at Day ...

5. womensmentalhealth.org womensmentalhealth.org/posts/phase-2-clinical-trial-novel-psychedelic-for-the-treatment-of-ppd/

Phase 2 Clinical Trial Examines the Efficacy of a Novel ... According to Reunion Neuroscience, data from a Phase 1 clinical trial indicated that RE104 produced a “psychedelic state similar in intensity ...

6. psychiatrist.com psychiatrist.com/news/reunions-novel-therapy-shows-promise-for-postpartum-depression/

Reunion's Novel Therapy Shows Promise for Postpartum ... The safety data the study produced appeared to be just as encouraging. The researchers noted that RE104 was generally well tolerated, with ...

7. ctv.veeva.com ctv.veeva.com/study/re104-safety-and-efficacy-study-in-postpartum-depression

RE104 Safety and Efficacy Study in Postpartum Depression The purpose of this study is to determine if treatment with a single dose of RE104 for Injection reduces depressive symptoms in participants ...