NORA520 for Postpartum Depression

(NuMom Trial)

No longer recruiting at 38 trial locations

Overseen By Clinical Trial Team

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: DuKang Pharmaceuticals, Inc.

Must not be taking: Antidepressants, Antipsychotics

Disqualifiers: Bipolar, Schizophrenia, Psychosis, others

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

Compensation: Varies

Number of Visits: 3

Duration: 3 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called NORA520 (an allopregnanolone prodrug) to determine its effectiveness for women with severe postpartum depression (PPD), a type of depression that can occur after childbirth. The study will assess drug tolerance, side effects, and its impact on reducing depressive symptoms. It will also measure the drug's concentration in blood and breastmilk. Participants will be randomly assigned to one of three groups, receiving either a low dose, a high dose, or a placebo for three days. Women who have experienced a depressive episode soon after giving birth and are less than nine months postpartum may be suitable for this trial. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to early-stage findings.

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.

Is there any evidence suggesting that NORA520 is likely to be safe for humans?

Research suggests that NORA520, a new treatment being tested for severe postpartum depression, might be safe. Patients who have used similar treatments, like brexanolone, have mostly experienced mild side effects. Studies have shown that these treatments can greatly reduce depression symptoms.

NORA520 is currently in a Phase 2 clinical trial. Researchers are still learning about its tolerability and potential side effects. Typically, drugs in this phase have shown some safety in earlier trials but require further testing for confirmation.

In short, while NORA520 appears promising, more research is needed to fully understand its safety. ^{1 2 3 4 5}

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

NORA520 is unique because it offers a potential new way to treat postpartum depression. Current treatments often rely on antidepressants like SSRIs or psychotherapy, which can take weeks to show effects. NORA520 is believed to work faster, possibly providing relief in just days, which is crucial for new mothers needing quick support. Additionally, it might have a different mechanism of action, which could offer benefits to those who don’t respond well to existing medications. Researchers are excited because if successful, NORA520 could become a faster-acting option for postpartum depression, improving the quality of life for many women.

What evidence suggests that NORA520 might be an effective treatment for postpartum depression?

Research has shown that treatments like NORA520, which participants in this trial may receive, have been promising in easing symptoms of postpartum depression (PPD). Similar treatments, such as zuranolone and brexanolone, have lowered depression levels in just a few days by affecting certain brain receptors that help control mood. The success of these treatments, along with their mild side effects, suggests that NORA520 could be helpful for those with severe PPD. Early results from similar drugs offer hope for its effectiveness. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• NORA520

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.

How Is the Trial Designed?

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?

DuKang Pharmaceuticals, Inc.

Lead Sponsor

Gerbera Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

90+

Published Research Related to This Trial

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 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 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]

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]

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, 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9088875/

Allopregnanolone in Postpartum Depression - PMC Zuranolone administered at the dose of 30 mg for 2 weeks significantly improved the Hamilton depression rating scale (HAMD-17) scores 3 days ...

2. nimh.nih.gov nimh.nih.gov/news/science-updates/2024/basic-research-powers-the-first-medication-for-postpartum-depression

Basic Research Powers the First Medication for Postpartum ... Brexanolone significantly and meaningfully reduced PPD symptoms , and it had only mild side effects. Compared to usual depression treatments, ...

3. nature.com nature.com/articles/s41386-023-01721-1

Novel neurosteroid therapeutics for post-partum depression This article reviews novel neurosteroid therapeutics for post-partum depression, with a focus on their development, clinical trial data, current practices, and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2352289520300023

Allopregnanolone in postpartum depression: Role ... In this review, we focus on the potential role of GABAergic signaling and the GABA A receptor positive allosteric modulator allopregnanolone in PPD.

5. mdpi.com mdpi.com/1660-4601/22/4/546

Rapid-Acting Treatments for Perinatal Depression Results demonstrated significant reductions in depression severity ratings with active treatment compared to sham over the one-month treatment time, with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06285916

NCT06285916 | A Study to Assess the Efficacy, Safety, and ... A Study to Assess the Efficacy, Safety, and Tolerability of Oral NORA520 in Adults With Severe Postpartum Depression (NuMom). ClinicalTrials.gov ID NCT06285916.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7231991/

Allopregnanolone in postpartum depression: Role in ... In this review, we focus on the potential role of GABAergic signaling and the GABA A receptor positive allosteric modulator allopregnanolone in PPD.

8. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06285916/

Trial | NCT06285916 The purpose of this research study is to test the study drug, NORA520, as a possible treatment for severe postpartum depression (PPD).