Study of Efficacy, Safety, Tolerability and Pharmacokinetics of MIJ821 in Participants With Treatment- Resistant Depression (TRD)

A Randomized, Double-blind, Placebo-controlled, Parallel-group Trial to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Single Subcutaneous MIJ821 Injection in Addition to Standard of Care in Participants With Treatment-resistant Depression

The main purpose of this study was to evaluate safety and efficacy of a single injection of MIJ821 in addition to standard of care (SoC) pharmacological anti-depressant treatment in participants with treatment-resistant depression (TRD)

Study Overview

• Status: Completed
• Conditions: Treatment-Resistant Depression
• Intervention / Treatment: Drug: MIJ821 Subcutaneous Injection 1 mg; Drug: MIJ821 Subcutaneous Injection 4 mg; Drug: MIJ821 Subcutaneous Injection 10 mg; Drug: Placebo Subcutaneous Injection

Detailed Description

The trial included a screening period of up to 28 days. On Day 1, after screening, eligible participants were randomized to one of the treatment arms (1 mg, 4 mg, or 10 mg of MIJ821) or placebo and received study treatment administered as a single subcutaneous injection. Participants remained at the clinic for at least 4 hours after administration of study treatment for safety observation including assessment of local tolerability by visual inspection of the injection area. Post-dose clinic visits occurred 24 hours post dose (Day 2), Days 8, 15, 22 and 29 to evaluate efficacy and safety. Efficacy assessments included the Montgomery-Asberg Depression Scale (MADRS) and other clinical outcome assessments (COAs). Safety assessments included laboratory tests, ECGs, vital signs and physical examinations. In addition, phone calls were conducted 3 days after each on-site clinic visit with the exception of the End-of-study (EOS) visit. EOS visit was completed on site on Day 29. Including screening, participants were in the study for up to 8 weeks (57 days).

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Kanagawa
    • Yokohama-city, Kanagawa, Japan, 236-0004
      • Novartis Investigative Site
  • Tokyo
    • Kodaira, Tokyo, Japan, 187-8551
      • Novartis Investigative Site
    • Mitaka-city, Tokyo, Japan, 181-8611
      • Novartis Investigative Site
• Poland
  • Bialystok, Poland, 15 276
    • Novartis Investigative Site
  • Gdansk, Poland, 80 952
    • Novartis Investigative Site
  • Swiecie North West, Poland, 86-100
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Barcelona, Spain, 08025
    • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Novartis Investigative Site
    • Sant Boi de Llobregat, Barcelona, Spain, 08830
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • 25Uni of Alabama at Birmingham
  • Florida
    • Oakland Park, Florida, United States, 33334
      • Research Centers of America LLC
    • Tampa, Florida, United States, 33629
      • Interventional Psychiatry Tampa Bay

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent obtained prior to participation in the study
• Male and female participants, 18 to 65 years of age (inclusive) at screening
• DSM-5 defined major depressive disorder (MDD) and a current major depressive episode (MDE)
• MADRS score ≥ 24
• Failure to respond to 2 or more antidepressant treatments where the two failed treatments are two different antidepressants

Exclusion Criteria:

• Any prior or current diagnosis of MDD with psychotic features, bipolar disorder, schizophrenia, or schizoaffective disorder
• Participants with acute alcohol or substance use disorder or withdrawal symptoms requiring detoxification, or participants who went through detoxification treatment within 1 month before Screening
• Participants with current borderline personality disorder or antisocial personality disorder
• Current clinical diagnosis of autism, dementia, or intellectual disability

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MIJ821 1 mg; Participants received a single dose of 1 mg MIJ821 administered as a subcutaneous (SC) injection on Day 1.	Drug: MIJ821 Subcutaneous Injection 1 mg; MIJ821 supplied in vials as a powder for solution for injection, reconstituted and administered as a single SC injection on Day 1.
Experimental: MIJ821 4 mg; Participants received a single dose of 4 mg MIJ821 administered as an SC injection on Day 1.	Drug: MIJ821 Subcutaneous Injection 4 mg; MIJ821 supplied in vials as a powder for solution for injection, reconstituted and administered as a single SC injection on Day 1.
Experimental: MIJ821 10 mg; Participants received a single dose of 10 mg MIJ821 administered as an SC injection on Day 1.	Drug: MIJ821 Subcutaneous Injection 10 mg; MIJ821 supplied in vials as a powder for solution for injection, reconstituted and administered as a single SC injection on Day 1.
Placebo Comparator: Placebo; Participants received a single dose of 0.9% sodium chloride solution administered as an SC injection on Day 1.	Drug: Placebo Subcutaneous Injection; 0.9% sodium chloride solution administered as a single SC injection on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score 24 Hours (Day 2) After Injection	The Montgomery Åsberg Depression Rating Scale (MADRS, SIGMA version), is a clinician rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 0 - 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts and suicidal thoughts. The MADRS scores were collected electronically by qualified personnel.	Baseline and 24 hours after SC injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Including Adverse Events of Special Interest (AESIs)	A TEAE was defined as an adverse event starting or worsening after the administration of study medication and up to the end of study visit. The following events were considered AESIs: Dissociation; Sedation; Cardiovascular effects (Blood Pressure changes and QT interval prolongation on electrocardiogram [ECG]); Respiratory effects (difficulty in breathing, changes in oxygen saturation); Suicidality (suicidal ideation or behavior); Memory gaps/amnesia; Cystitis or lower urinary tract adverse events	From Day 1 after SC injection to end of study, up to 29 Days
Pharmacokinetics (PK) of MIJ821 in Plasma for Area Under the Curve From the Time of Dosing to the Time of the Last Measurable Concentration (AUClast)	Blood samples were collected at the indicated time points for PK analysis. AUClast was defined as the area under the curve from time zero to the last measurable concentration sampling time (tlast).	Baseline, 0.17 hour, 0.33 hour, 0.5 hour, 0.75 hour, 1, 1.5, 2, 4 and 24 hours post injection
PK of MIJ821 in Plasma for Maximum Serum Concentration (Cmax)	Blood samples were collected at the indicated time points for PK analysis. Cmax was defined as the maximum (peak) observed plasma drug concentration after single dose administration.	Baseline, 0.17 hour, 0.33 hour, 0.5 hour, 0.75 hour, 1, 1.5, 2, 4 and 24 hours post injection
PK of MIJ821 in Plasma for Time to Maximum Drug Concentration (Tmax)	Blood samples were collected at the indicated time points for PK analysis. Tmax was defined as the time to reach maximum (peak) plasma drug concentration after single dose administration (time).	Baseline, 0.17 hour, 0.33 hour, 0.5 hour, 0.75 hour, 1, 1.5, 2, 4 and 24 hours post injection
Change From Baseline in the MADRS Total Scores at Day 8, 15, 22 and 29 Visits	The MADRS (SIGMA version), is a clinician rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 0 - 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts and suicidal thoughts. The MADRS scores were collected electronically by qualified personnel.	Baseline, Days 8, 15, 22 and 29
Dose-response (DR) Relationship of MIJ821 With Respect to Change From Baseline in MADRS Total Score at 24 Hours After Single SC Injection	The multiple comparison procedure - modelling (MCP-Mod) approach was an integrated approach used to investigate DR relationships, while confirming efficacy of the test product based on hypothesis testing. A set of candidate models was tested using Multiple Comparison Procedures (MCP) that preserve the family-wise error rate (FWER) to determine the model best representing the underlying DR. Efficacy via DR was established when at least one of the model tests was significant.	Baseline up to 24 Hours
Exposure-response Relationship of MIJ821 With Respect to Change From Baseline in MADRS Total Score. Estimated Parameters: Placebo Effect E0, Emax	The exposure-response relationship was investigated considering PK exposure parameters (AUClast and Cmax) and the change from baseline MADRS score derived at 4 h and 24 h after injection and Day 8, Day 15, Day 22 and Day 29 during the follow-up. The emax model or sigmoid emax model were planned to be fitted for the change from baseline at each follow up visit and the PK exposure parameters, Cmax and AUClast. If the model converges, parameters estimated from the Sigmoid emax model are: the placebo effect E0, EC50, Emax and the hill parameter.	Baseline, Day 2, 15, 22 and 29
Exposure-response Relationship of MIJ821 With Respect to Change From Baseline in MADRS Total Score. Estimated Parameter: EC50 (Cmax)	The exposure-response relationship was investigated considering PK exposure parameters (AUClast and Cmax) and the change from baseline MADRS score derived at 4 h and 24 h after injection and Day 8, Day 15, Day 22 and Day 29 during the follow-up. The emax model or sigmoid emax model were planned to be fitted for the change from baseline at each follow up visit and the PK exposure parameters, Cmax and AUClast. If the model converges, parameters estimated from the Sigmoid emax model are: the placebo effect E0, EC50, Emax and the hill parameter.	Baseline, Day 2, 15, 22 and 29
Exposure-response Relationship of MIJ821 With Respect to Change From Baseline in MADRS Total Score. Estimated Parameter: EC50 (AUClast)	The exposure-response relationship was investigated considering PK exposure parameters (AUClast and Cmax) and the change from baseline MADRS score derived at 4 h and 24 h after injection and Day 8, Day 15, Day 22 and Day 29 during the follow-up. The emax model or sigmoid emax model were planned to be fitted for the change from baseline at each follow up visit and the PK exposure parameters, Cmax and AUClast. If the model converges, parameters estimated from the Sigmoid emax model are: the placebo effect E0, EC50, Emax and the hill parameter.	Baseline, Day 2, 15, 22 and 29
Exposure-response Relationship of MIJ821 With Respect to Change From Baseline in MADRS Total Score. Estimated Parameter: Hill Parameter	The exposure-response relationship was investigated considering PK exposure parameters (AUClast and Cmax) and the change from baseline MADRS score derived at 4 h and 24 h after injection and Day 8, Day 15, Day 22 and Day 29 during the follow-up. The emax model or sigmoid emax model were planned to be fitted for the change from baseline at each follow up visit and the PK exposure parameters, Cmax and AUClast. If the model converges, parameters estimated from the Sigmoid emax model are: the placebo effect E0, EC50, Emax and the hill parameter.	Baseline, Day 2, 15, 22 and 29

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2023
• Primary Completion (Actual): November 28, 2023
• Study Completion (Actual): November 28, 2023

Study Registration Dates

• First Submitted: June 16, 2022
• First Submitted That Met QC Criteria: July 8, 2022
• First Posted (Actual): July 12, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Subcutaneous; Adult; Major Depressive Disorder; Placebo; Major Depressive Episode; Treatment-Resistant Depression; MIJ821; Anti-depressive Agent
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: CMIJ821B12201; 2021-005992-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No