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

Treatment-Resistant Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05454410
• Other study ID #: CMIJ821B12201
• Secondary ID: 2021-005992-38
• Status: Completed
• Phase: Phase 2
• Start date: March 13, 2023
• Est. completion date: November 28, 2023

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is 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)

Description:

Approximately 56 participants will be randomized in a total of 20-25 centers worldwide. The trial consists of screening period of up to 28 days. On Day 1, eligible participants will be randomized to one of the treatment arms (low, medium or high dose of MIJ821) or placebo and receive study treatment administered as a single subcutaneous injection. Participant will remain 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 will occur 24 hours post dose (Day 2), Days 8, 15, 22 and 29 to evaluate efficacy and safety. Efficacy assessments will include the Montgomery-Asberg Depression Scale (MADRS) and other clinical outcome assessments (COAs). Safety assessments include laboratory tests, ECGs, vital signs and physical examinations. In addition phone calls will be conducted 3 days after each on-site clinic visit with the exception of End-of-study (EOS) visit. EOS visit will be completed on site on Day 29. The total duration of the study is approximately 8 weeks (56 days), including screening.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: November 28, 2023
• Est. primary completion date: November 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Signed informed consent must be 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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant
• Treatment-Resistant Depression

Intervention

Drug:
• MIJ821 Subcutaneous Injection - low dose
MIJ821 supplied in vials as a powder for solution for injection, to be reconstituted, and administered as a single subcutaneous injection on Day 1
• MIJ821 Subcutaneous Injection - medium dose
MIJ821 supplied in vials as a powder for solution for injection, to be reconstituted, and administered as a single subcutaneous injection on Day 1
• MIJ821 Subcutaneous Injection - high dose
MIJ821 supplied in vials as a powder for solution for injection, to be reconstituted, and administered as a single subcutaneous injection on Day 1
• Placebo Subcutaneous Injection
0.9% sodium chloride solution to be administered as a single subcutaneous injection on Day 1

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Kodaira	Tokyo
Japan	Novartis Investigative Site	Mitaka-city	Tokyo
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Swiecie n/W
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Pamplona	Navarra
Spain	Novartis Investigative Site	Sabadell	Barcelona
Spain	Novartis Investigative Site	Sant Boi de Llobregat	Barcelona
Spain	Novartis Investigative Site	Sevilla	Andalucia
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Research Centers of America LLC .	Oakland Park	Florida
United States	Interventional Psychiatry Tampa Bay	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Japan,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in MADRS total score 24 hours after injection	The Montgomery Asberg 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 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 will be collected electronically by qualified personnel.	Baseline and 24 hours after s.c. injection
Secondary	Number of treatment-emergent adverse events (TEAEs), including AEs of special interest (AESIs)	Number of treatment-emergent adverse events (TEAEs), including AEs of special interest (AESIs) will be collected at all study visits. AESIs include dissociation, sedation, cardiovascular and respiratory effect, suicidality, memory gaps/amnesia, cystitis or lower urinary tract adverse events	Baseline up to 29 days
Secondary	Pharmacokinetics (PK) of MIJ821 in plasma for AUClast	AUClast is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1)	Baseline, 0.17 hour, 0.33 hour, 0.5 hour, 0.75 hour, 1, 1.5, 2, 4 and 24 hours post injection
Secondary	Pharmacokinetics (PK) of MIJ821 in plasma for Cmax	Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)	Baseline, 0.17 hour, 0.33 hour, 0.5 hour, 0.75 hour, 1, 1.5, 2, 4 and 24 hours post injection
Secondary	Pharmacokinetics (PK) of MIJ821 in plasma for Tmax	Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid 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
Secondary	MADRS total scores	The Montgomery Asberg 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 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 will be collected electronically by qualified personnel.	Baseline, Day 8, Day 15, Day 22 and 29
Secondary	Dose-response relationship of MIJ821	Correlation between MIJ821 dose and change from baseline in the Montgomery Asberg Depression Rating Scale (MADRS) total score at 24 hours. The MADRS 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 60. Higher scores represent a more severe condition.	Baseline up to 24 hours
Secondary	Exposure-response relationship of MIJ821	Correlation between MIJ821 exposure and the Montgomery Asberg Depression Rating Scale (MADRS) total score at 24 hours. MADRS 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 60. Higher scores represent a more severe condition.	Baseline up to 24 hours