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

• ClinicalTrials.gov Identifier: NCT05454410
• Recruitment Status: Recruiting
• First Posted: July 12, 2022
• Last Update Posted: January 9, 2023
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief 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)

Condition or disease	Intervention/treatment	Phase
Treatment-Resistant Depression	Drug: MIJ821 Subcutaneous Injection - low dose; Drug: MIJ821 Subcutaneous Injection - medium dose; Drug: MIJ821 Subcutaneous Injection - high dose; Drug: Placebo Subcutaneous Injection	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: January 31, 2023
• Estimated Primary Completion Date: August 16, 2023
• Estimated Study Completion Date: September 13, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: MIJ821 - low dose; Single subcutaneous administration of low dose of MIJ821 on Day 1	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
Experimental: MIJ821 - medium dose; Single subcutaneous administration of medium dose of MIJ821 on Day 1	Drug: 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
Experimental: MIJ821 - high dose; Single subcutaneous administration of high dose of MIJ821 on Day 1	Drug: 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 Comparator: Placebo; Single subcutaneous administration of 0.9% sodium chloride on Day 1	Drug: Placebo Subcutaneous Injection; 0.9% sodium chloride solution to be administered as a single subcutaneous injection on Day 1

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in MADRS total score 24 hours after injection [ Time Frame: Baseline and 24 hours after s.c. 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.

Secondary Outcome Measures :

1. Number of treatment-emergent adverse events (TEAEs), including AEs of special interest (AESIs) [ Time Frame: Baseline up to 29 days ]
   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
2. Pharmacokinetics (PK) of MIJ821 in plasma for AUClast [ Time Frame: Baseline, 0.17 hour, 0.33 hour, 0.5 hour, 0.75 hour, 1, 1.5, 2, 4 and 24 hours post injection ]
   AUClast is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1)
3. Pharmacokinetics (PK) of MIJ821 in plasma for Cmax [ Time Frame: Baseline, 0.17 hour, 0.33 hour, 0.5 hour, 0.75 hour, 1, 1.5, 2, 4 and 24 hours post injection ]
   Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)
4. Pharmacokinetics (PK) of MIJ821 in plasma for Tmax [ Time Frame: Baseline, 0.17 hour, 0.33 hour, 0.5 hour, 0.75 hour, 1, 1.5, 2, 4 and 24 hours post injection ]
   Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
5. MADRS total scores [ Time Frame: Baseline, Day 8, Day 15, Day 22 and 29 ]
   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.
6. Dose-response relationship of MIJ821 [ Time Frame: Baseline up to 24 hours ]
   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.
7. Exposure-response relationship of MIJ821 [ Time Frame: Baseline up to 24 hours ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals; +41613241111

Locations

United States, Florida

Novartis Investigative Site; Recruiting

Oakland Park, Florida, United States, 33334

United States, New Jersey

Novartis Investigative Site; Recruiting

Berlin, New Jersey, United States, 08009

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05454410
• Other Study ID Numbers: CMIJ821B12201; 2021-005992-38 ( EudraCT Number )
• First Posted: July 12, 2022
• Last Update Posted: January 9, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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 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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Treatment-Resistant Depression; Major Depressive Episode; Major Depressive Disorder; MIJ821; Anti-depressive Agent; Subcutaneous; Placebo; Adult

Additional relevant MeSH terms:

Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Behavioral Symptoms; Mood Disorders; Mental Disorders