Clinical trial NCT05454410: Study of Efficacy, Safety, Tolerability and Pharmacokinetics of MIJ821 in Participants With Treatment- Resistant Depression (TRD)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Treatment-Resistant Depression
Keywords: Treatment-Resistant Depression
Major Depressive Episode
Major Depressive Disorder
MIJ821
Anti-depressive Agent
Subcutaneous
Placebo
Adult
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-07-12
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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)

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).

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score 24 Hours (Day 2) After Injection
timeFrame: Baseline and 24 hours after SC injection
Secondary outcomes:
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Including Adverse Events of Special Interest (AESIs)
timeFrame: From Day 1 after SC injection to end of study, up to 29 Days
measure: 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)
timeFrame: Baseline, 0.17 hour, 0.33 hour, 0.5 hour, 0.75 hour, 1, 1.5, 2, 4 and 24 hours post injection
measure: PK of MIJ821 in Plasma for Maximum Serum Concentration (Cmax)
timeFrame: Baseline, 0.17 hour, 0.33 hour, 0.5 hour, 0.75 hour, 1, 1.5, 2, 4 and 24 hours post injection
measure: PK of MIJ821 in Plasma for Time to Maximum Drug Concentration (Tmax)
timeFrame: Baseline, 0.17 hour, 0.33 hour, 0.5 hour, 0.75 hour, 1, 1.5, 2, 4 and 24 hours post injection
measure: Change From Baseline in the MADRS Total Scores at Day 8, 15, 22 and 29 Visits
timeFrame: Baseline, Days 8, 15, 22 and 29
measure: Dose-response (DR) Relationship of MIJ821 With Respect to Change From Baseline in MADRS Total Score at 24 Hours After Single SC Injection
timeFrame: Baseline up to 24 Hours
measure: Exposure-response Relationship of MIJ821 With Respect to Change From Baseline in MADRS Total Score. Estimated Parameters: Placebo Effect E0, Emax
timeFrame: Baseline, Day 2, 15, 22 and 29
measure: Exposure-response Relationship of MIJ821 With Respect to Change From Baseline in MADRS Total Score. Estimated Parameter: EC50 (Cmax)
timeFrame: Baseline, Day 2, 15, 22 and 29
measure: Exposure-response Relationship of MIJ821 With Respect to Change From Baseline in MADRS Total Score. Estimated Parameter: EC50 (AUClast)
timeFrame: Baseline, Day 2, 15, 22 and 29
measure: Exposure-response Relationship of MIJ821 With Respect to Change From Baseline in MADRS Total Score. Estimated Parameter: Hill Parameter
timeFrame: Baseline, Day 2, 15, 22 and 29
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: 25Uni of Alabama at Birmingham
state: Alabama
city: Oakland Park
country: United States
facility: Research Centers of America LLC
state: Florida
city: Tampa
country: United States
facility: Interventional Psychiatry Tampa Bay
state: Florida
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kodaira
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Mitaka-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Swiecie North West
country: Poland
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Sant Boi de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: