A Study to Assess the Efficacy, Safety, and Tolerability of Oral NORA520 in Adults With Severe Postpartum Depression (NuMom)

A Randomized, Placebo-Controlled, Double-Blinded, Phase 2 Study to Evaluate the Efficacy, Safety, and Tolerability of Oral NORA520 in Female Adults With Severe Postpartum Depression

The purpose of this research study is to test the study drug, NORA520, as a possible treatment for severe postpartum depression (PPD). The trial aims to determine:

• How well NORA520 is tolerated and what side effects it may cause
• If NORA520 reduces depressive symptoms in subjects with severe PPD
• The amount of NORA520 in the blood at various times after taking the study drug; this provides information that helps determine how often NORA520 should be taken
• In a subset of subjects, the amount of NORA520 in breastmilk at various times after taking it to determine if and how much NORA520 can pass into breastmilk Participate in this study will be randomly assigned to one of 3 different groups. All subjects will take the study drug for 3 days.

Study Overview

• Status: Completed
• Conditions: Postpartum Depression; Depression, Postpartum; Postnatal Depression; Post-partum Depression; Post-Natal Depression
• Intervention / Treatment: Drug: NORA520 Dose 1; Drug: NORA520 Dose 2; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Pillar Clinical Research
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center
    • Canoga Park, California, United States, 91304
      • Alliance Research Institute
    • Sherman Oaks, California, United States, 91403
      • CenExel Clinical Research
    • Torrance, California, United States, 90504
      • CenExel Clinical Research
  • Florida
    • Miami, Florida, United States, 33145
      • MedOne Clinical Research
    • Miami Gardens, Florida, United States, 33014
      • Meridian International Research, Inc.
    • Orlando, Florida, United States, 32807
      • Combined Research
    • Pompano Beach, Florida, United States, 33060
      • Clinical Research Center of Florida
    • St. Petersburg, Florida, United States, 33607
      • GCP Research
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • CenExel Clinical Research
    • Decatur, Georgia, United States, 30030
      • CenExel Clinical Research
    • Savannah, Georgia, United States, 31405
      • CenExel Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60616
      • Insight Hospital and Medical Center Chicago
  • New York
    • Glen Oaks, New York, United States, 11004
      • Zucker Hillside Hospital
  • North Carolina
    • Monroe, North Carolina, United States, 28112
      • Monroe Biomedical Research
  • Texas
    • League City, Texas, United States, 77573
      • Maximos Ob/Gyn
    • Richardson, Texas, United States, 75080
      • Pillar Clinical Researc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Are willing and able to provide signed informed consent to participate in the study and to comply with all study procedures and scheduled visits
• Are an adult female between 18 and 45 years of age, inclusive;
• Have either ceased lactating at Screening, or if still lactating or actively breastfeeding at Screening, agree to temporarily cease giving breastmilk to their infant(s) from just prior to first dose of study drug on Day 1 through Day 14;
• Have a negative pregnancy test at Screening and Day 1 (prior to dosing);
• Have had a depressive episode that began no earlier than the third trimester and no later than the first 4 weeks following delivery
• Are ≤9 months postpartum at Screening.

Key Exclusion Criteria:

• Have a history or current diagnosis or current treatment of bipolar disorder, schizophrenia, or schizoaffective disorder;
• Have had recorded treatment failure of ≥2 different antidepressant classes (e.g., SSRI, SNRI) in the current or previous episode;
• Are currently experiencing active psychosis per Investigator assessment, or are taking typical or atypical antipsychotic medication;
• Have a history of suicidal behavior within 2 years;
• Have a history or current diagnosis of sleep apnea or narcolepsy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NORA520 Tablets Dose 1	Drug: NORA520 Dose 1; Oral NORA520 tablets Dose 1 for 3 days
Experimental: NORA520 Tablets Dose 2	Drug: NORA520 Dose 2; Oral NORA520 tablets Dose 2 for 3 days
Placebo Comparator: Placebo Tablets	Drug: Placebo; Oral Placebo tablets for 3 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity, and causality of AEs, SAEs, and AESIs	Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs)	Up to Day 30
Change from baseline in HAM-D17 total score compared to placebo	The Seventeen-Item Hamilton Rating Scale for Depression (HAM-D17) contains 17 individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia (initial, middle, and late), work and interests, psychomotor retardation, psychomotor agitation, anxiety (psychic and somatic), gastrointestinal symptoms, general somatic symptoms, sexual interest, hypochondriasis, insight, and weight loss. The total score ranges from 0 to 52, with higher scores indicating more severe depression.	Baseline to Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Edinburgh Postnatal Depression Scale (EPDS) total score	The Edinburgh Postnatal Depression Scale (EPDS) is a set of 10 screening questions. The total score ranges from 0 to 30, with higher scores indicating more severe depression.	Baseline to Days 8 and 30
Number of patients who start any new antidepressant or anti-anxiety medication		After Day 8 assessments through Day 30
Change from baseline in HAM-D17 total score	The Seventeen-Item Hamilton Rating Scale for Depression (HAM-D17) contains 17 individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia (initial, middle, and late), work and interests, psychomotor retardation, psychomotor agitation, anxiety (psychic and somatic), gastrointestinal symptoms, general somatic symptoms, sexual interest, hypochondriasis, insight, and weight loss. The total score ranges from 0 to 52, with higher scores indicating more severe depression.	Baseline to Days 8 and 30
HAM-D17 response	Defined as having a 50% or greater reduction from baseline in HAM-D17 total score. The total score ranges from 0 to 52, with higher scores indicating more severe depression.	Baseline to Days 4, 8, and 30
HAM-D17 remission	Defined as having a HAM-D17 total score ≤7. The total score ranges from 0 to 52, with higher scores indicating more severe depression.	Baseline to Days 4, 8, and 30
Change from baseline in HAM-D17 subscale and individual item scores	The Seventeen-Item Hamilton Rating Scale for Depression (HAM-D17) contains 17 individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia (initial, middle, and late), work and interests, psychomotor retardation, psychomotor agitation, anxiety (psychic and somatic), gastrointestinal symptoms, general somatic symptoms, sexual interest, hypochondriasis, insight, and weight loss. The total score ranges from 0 to 52, with higher scores indicating more severe depression.	Baseline to Days 4, 8, and 30
Change from baseline in Clinical Global Impression - Severity (CGI-S) score	The CGI-S scale is a 7-point scale that requires the Investigator to assess how mentally ill is the patient at this time. 1 - normal, not at all ill; 2 - borderline mentally ill; 3 - mildly ill; 4 - moderately ill; 5 - markedly ill; 6 - severely ill; or 7 - among the most extremely ill patients.	Baseline to Days 4, 8, and 30
Clinical Global Impression - Improvement (CGI-I) scale positive response	The CGI-I scale is a 7-point scale that requires the Investigator to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of study drug treatment. 1 - very much improved; 2 - much improved; 3 - minimally improved; 4 - no change; 5 - minimally worse; 6 - much worse; or 7 - very much worse	Baseline to Days 4, 8, and 30
Change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score	The MADRS contains 10 individual items related to the following symptoms: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. The total score ranges from 0 to 60, with higher scores indicating more severe depression.	Baseline to Days 4, 8, and 30
Change from baseline in Hamilton Anxiety Rating Scale (HAM-A) total score	The HAM-A contains 14 individual ratings related to the following symptoms: anxious mood, tension, fears, insomnia, intellectual, depressed mood, somatic (muscular), somatic (sensory), cardiovascular symptoms, respiratory symptoms, gastrointestinal symptoms, genitourinary symptoms, autonomic symptoms, and behavior at interview. The total score ranges from 0 to 56, with higher scores indicating more severe anxiety.	Baseline to Days 4, 8, and 30

Collaborators and Investigators

• Sponsor: TWi Biotechnology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2024
• Primary Completion (Actual): September 11, 2025
• Study Completion (Actual): October 6, 2025

Study Registration Dates

• First Submitted: February 17, 2024
• First Submitted That Met QC Criteria: February 22, 2024
• First Posted (Actual): February 29, 2024

Study Record Updates

• Last Update Posted (Actual): July 31, 2026
• Last Update Submitted That Met QC Criteria: July 30, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Depression; Postpartum Depression; Postnatal Depression; NORA520; NuMom
• Additional Relevant MeSH Terms: Urogenital Diseases; Mental Disorders; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Behavioral Symptoms; Mood Disorders; Puerperal Disorders; Depressive Disorder; Behavior; Depression; Depression, Postpartum; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: NORA520-PT-US-1a

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No