NORA520 for Postpartum Depression

(NuMom Trial)

Recruiting at19 trial locations

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Gerbera Therapeutics, Inc.

Must not be taking: Antidepressants, Antipsychotics

Disqualifiers: Bipolar, Schizophrenia, Psychosis, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a drug called NORA520 to see if it can help women with severe postpartum depression. The study will check how well the drug works, its side effects, and how much of it gets into the blood and breastmilk. Women in the study will take the drug for a short period.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking antipsychotic medications, you may not be eligible to participate.

What data supports the effectiveness of the drug NORA520 for postpartum depression?

Research on brexanolone, a drug similar to NORA520, shows it is effective in treating postpartum depression by stabilizing hormone levels and reducing depression symptoms. Brexanolone, which is an allopregnanolone formulation like NORA520, has been shown to significantly reduce depression scores in clinical trials. ^{1 2 3 4 5}

Is NORA520 (Allopregnanolone prodrug) safe for humans?

Brexanolone, an intravenous form of allopregnanolone, has been tested in several studies for postpartum depression and is generally considered safe when administered under medical supervision, with monitoring during the 60-hour infusion. ^{1 2 3 5 6}

How is the drug NORA520 different from other treatments for postpartum depression?

NORA520 is unique because it is an allopregnanolone prodrug, similar to brexanolone, which is the first FDA-approved drug specifically for postpartum depression. Unlike traditional antidepressants, it works by modulating GABA-A receptors, potentially offering rapid relief from symptoms. ^{1 2 3 4 7}

Research Team

Eligibility Criteria

This trial is for adults with severe postpartum depression. Participants will be randomly assigned to one of three groups and will take the study drug or placebo for 3 days.

Inclusion Criteria

Negative pregnancy test at Screening and Day 1 (prior to dosing)

Willing and able to provide signed informed consent to participate in the study and to comply with all study procedures and scheduled visits

I gave birth less than 9 months ago.

Exclusion Criteria

I have been diagnosed with sleep apnea or narcolepsy.

History of suicidal behavior within 2 years

I am not currently experiencing psychosis nor taking antipsychotic medication.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the study drug, NORA520, for 3 days to assess its efficacy, safety, and tolerability in treating severe postpartum depression

3 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at Days 4, 8, and 30

4 weeks

3 visits (in-person or virtual)

Treatment Details

Interventions

• NORA520 (Other)

Trial Overview The study tests NORA520's effectiveness in reducing depressive symptoms, its safety, tolerability, how it's processed by the body, and if it transfers into breastmilk. There are two different doses of NORA520 being compared against a placebo.

Participant Groups

Group I: NORA520 Tablets Dose 2 Experimental Treatment 1 Intervention

NORA520 Tablets Dose 2

Group II: NORA520 Tablets Dose 1 Experimental Treatment 1 Intervention

NORA520 Tablets Dose 1

Group III: Placebo Tablets Placebo Group 1 Intervention

Placebo Tablets

Who Is Running the Clinical Trial?

Gerbera Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

90+

Findings from Research

Brexanolone is the first FDA-approved medication specifically for postpartum depression, utilizing allopregnanolone to stabilize hormone levels that drop after childbirth, which may contribute to the condition.

Administered as a continuous intravenous infusion over 60 hours, brexanolone works by modulating neuronal excitability, showing promising efficacy and tolerability in clinical trials for treating postpartum depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous brexanolone for postpartum depression: what it is, how well does it work, and will it be used? Faden, J., Citrome, L.[2020]

Brexanolone is the first FDA-approved medication specifically for postpartum depression (PPD), showing significant efficacy in reducing depression scores in three randomized controlled trials with intravenous administration over 60 hours.

All studies demonstrated a statistically significant reduction in the Hamilton Rating Scale for Depression (HAM-D) scores compared to placebo, indicating brexanolone's effectiveness in treating moderate-to-severe PPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating Postpartum Depression: What Do We Know about Brexanolone? Ali, M., Aamir, A., Diwan, MN., et al.[2021]

Brexanolone infusion significantly reduces inflammatory markers such as TNF-α and IL-6 in postpartum depression patients, which correlates with improvements in depression scores, indicating its efficacy in treating PPD.

The treatment appears to work by inhibiting inflammatory responses to specific immune activators, suggesting that inflammation may play a role in postpartum depression and that targeting these pathways can enhance recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexanolone therapeutics in post-partum depression involves inhibition of systemic inflammatory pathways. Balan, I., Patterson, R., Boero, G., et al.[2023]

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]

Brexanolone infusion has been shown to provide a rapid antidepressant effect for postpartum depression (PPD), with significant improvements starting within 24 hours and lasting up to a week, based on data from 267 women in randomized controlled trials.

While brexanolone was more effective than placebo in reducing symptoms of PPD, it also had a higher rate of discontinuation for any reason, indicating that while it is effective, further research is needed to assess its long-term safety and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexanolone for postpartum depression: A meta-analysis of randomized controlled studies. Zheng, W., Cai, DB., Zheng, W., et al.[2020]

Brexanolone, an injectable formulation of allopregnanolone, was well tolerated in a small study of four women with severe postpartum depression (PPD), with no severe adverse events reported.

The treatment led to significant reductions in depression scores, indicating potential efficacy in rapidly alleviating symptoms of severe PPD, but further research in larger trials is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, proof-of-concept study of brexanolone in the treatment of severe postpartum depression. Kanes, SJ., Colquhoun, H., Doherty, J., et al.[2021]

Brexanolone, the only FDA-approved treatment for postpartum depression, shows a low relative infant dose (RID) of 1.3% when administered to breastfeeding mothers, indicating minimal exposure for infants through breast milk.

The pharmacokinetic study involving 12 lactating participants demonstrated that allopregnanolone concentrations in breast milk closely mirrored those in plasma, supporting the safety and efficacy of brexanolone dosing based on maternal weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allopregnanolone Concentrations in Breast Milk and Plasma from Healthy Volunteers Receiving Brexanolone Injection, With Population Pharmacokinetic Modeling of Potential Relative Infant Dose. Wald, J., Henningsson, A., Hanze, E., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Intravenous brexanolone for postpartum depression: what it is, how well does it work, and will it be used? [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Treating Postpartum Depression: What Do We Know about Brexanolone? [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Brexanolone therapeutics in post-partum depression involves inhibition of systemic inflammatory pathways. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

5. Ireland pubmed.ncbi.nlm.nih.gov

Brexanolone for postpartum depression: A meta-analysis of randomized controlled studies. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Open-label, proof-of-concept study of brexanolone in the treatment of severe postpartum depression. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Allopregnanolone Concentrations in Breast Milk and Plasma from Healthy Volunteers Receiving Brexanolone Injection, With Population Pharmacokinetic Modeling of Potential Relative Infant Dose. [2022]