The main purpose of the study is to support dose selection for future Phase 3 clinical trials by evaluating the efficacy and safety of four MIJ821 doses (0.0048, 0.016, 0.048 and 0.16 mg/kg) administered every other week by intravenous infusion on…
ID
Source
Brief title
Condition
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change from baseline in MADRS total score at 24 hours after the start of the
first infusion
Secondary outcome
* Number and severity of treatment-emergent adverse events
(TEAEs), including AEs of special interest in the Core Period
* Proportion of participants meeting response criteria (>=50%reduction from
baseline in MADRS total score) over time in the Core Period.
Proportion of participants meeting criteria
for sustained response (>=50% reduction from baseline in MADRS total score
sustained for a period of at least four weeks) in the Core Period
Proportion of participants meeting remission criteria (MADRS total score of
<=12) over time in the Core Period
Proportion of participants meeting criteria for sustained remission (MADRS
total score of <=12 sustained for a period of at least four weeks) in the Core
Period
Proportion of participants meeting criteria for relapse over all randomized
population over fixed period in the Extension Period Proportion of relapsing
participants meeting response criteria or remission criteria after the first
infusion of MIJ821 retreatment in the Extension Period
* PK parameters of MIJ821 in plasma after 1st infusion described
by AUClast, Cmax, Tmax (parameters not limited) and after each infusion
described by Cmax and Tmax.
Background summary
Depression is a serious and life-threatening condition with high rates of
morbidity and a chronic disease course. Major depressive disorder (MDD) is the
psychiatric diagnosis most commonly associated with suicide. Close to 800,000
people die due to suicide every year worldwide. The time between the onset of
suicidal ideation and suicide attempt is often very short and can be minutes or
a few days, highlighting the need for urgent intervention and development of
novel antidepressant therapies with a rapid onset. Concerted efforts over the
past 40 years have led to the introduction of safer, better tolerated, and
easier-to-prescribe antidepressants, most notably selective serotonin reuptake
inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).
Nevertheless, about 30 to 40% of patients with MDD fail to respond to
first-line treatments including oral antidepressant medications of all classes
(SSRIs, SNRIs, tricyclic antidepressants (TCAs, etc.) and psychotherapy. In
addition, the onset to treatment response, even when effective, often takes at
least four weeks, leading to greater suffering, expenses, and suicidal risk.
There remains an ongoing high need for rapid acting, either more effective or
better tolerated treatments that can in an effective way interrupt a depressive
episode, reduce suicidality, and also able to prevent future depressive
episodes.
Ketamine and esketamine (N-Methyl-D-Aspartate (NMDA) receptor antagonists) have
demonstrated a certain level of efficacy and showed a rapid mode of action,
their safety profile is not without adverse events that are meaningful for both
patients and clinicians. Targeting a specific subset of NMDA receptor (NMDAR)
is one approach to potentially mitigate adverse effects of NMDAR inhibition
while retaining antidepressant efficacy.
MIJ821 is a highly potent, selective and reversible low molecular weight
NR2B-NMDA receptor NAM. MIJ821 is intended to be studied as a short-term
treatment over 6 weeks in conjunction with pharmacological antidepressant SoC
treatment, for the rapid reduction of depressive symptoms in adult patients
with MDD who have suicidal ideation with intent. This treatment approach is
intended to allow these patients to rapidly achieve a significant improvement
of their depressive symptoms, and suicidal ideation.
Study objective
The main purpose of the study is to support dose selection for future Phase 3
clinical trials by evaluating the efficacy and safety of four MIJ821 doses
(0.0048, 0.016, 0.048 and 0.16 mg/kg) administered every other week by
intravenous infusion on top of pharmacological antidepressant treatment,
compared with placebo plus pharmacological antidepressant treatment, for the
rapid reduction of the symptoms of MDD in participants who have suicidal
ideation with intent. In addition, the study will explore the effect of single
dose administration of MIJ821 0.16 and 0.048 mg/kg to treat MDD in participants
who have suicidal ideation with intent.
The study will also have a 12-month Extension Period to explore durability of
the effect of the study treatment and the effect of MIJ821 on relapses rate, as
well as safety of repeated MIJ821 administration.
Study design
Double-blind, placebo-controlled, randomized dose-ranging trial. The study
consists of a Screening Period (up to 48 hrs), a double-blind Core Period (6
weeks) and an Extension Period (up to 52 weeks) for participants classified as
responders or remitters at the End of the Core Period.
Intervention
Intravenous MIJ821 administered as a 40-min infusion in addition to
comprehensive standard of care (SoC)
Treatment groups (2:1:2:2:2:2:2 ratio):
- placebo every other week
- MIJ821 0.0048 mg/kg every other week
- MIJ821 0.016 mg/kg every other week
- MIJ821 0.048 mg/kg every other week
- MIJ821 0.16 mg/kg every other week
- MIJ821 0.048 mg/kg single infusion with two subsequent placebo dosages given
every other week
- MIJ821 0.16 mg/kg single infusion with two subsequent placebo dosages given
every other week
Study burden and risks
Possible side effects of MIJ821:
• Very common side effects (affect about 1 in every 10 people): feeling dizzy,
feeling sleepy, feeling abnormal, increased blood pressure
• Common side effects (affects 1 in every 100 people): dissociative reactions
(feeling disconnected from yourself, your thoughts, feelings and things around
you), problem with memory, nausea
• ECG changes (with or without symptoms) and suicidal ideation have rarely been
reported.
• Risks from an IV include pain, swelling, redness, or infection at the IV
site. The side effects reappear within hours of the end of the infusion. If any
side effect persists, you may need to stay in hospital for longer for
observation until the side effect has resolved or stabilized.
Inconveniences and Risks of Investigation Tests and Procedures:
The examination tests are also used during the usual medical treatment.
• Blood samples: blood samples can hurt or bruise. Sometimes someone faints.
• An ECG from a Holter monitoring causes little or no discomfort of risk.
Participating in the study takes extra time for the subject.
The subject must be hospitalized.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
1. Signed informed consent must be obtained prior to participation in the
study.
2. Male and female participants, 18 to 65 years of age (inclusive) body weight
from 50 to 120 kg (inclusive) at screening.
3. DSM-5 defined major depressive disorder (MDD) with a current major
depressive episode (MDE) without psychotic features at the time of screening
based upon clinical assessment and confirmed by the Mini International
Neuropsychiatric Interview (M.I.N.I.) assessed at Screening.
4. Participants must have current suicidal ideation with intent, confirmed by
Yes-response to Question B3 AND either Question B10 or Question B11 obtained
from the M.I.N.I., assessed at Screening.
5. Current suicidal ideation with intent, confirmed by Yes-response to Question
3 AND either Question 9 or Question 10 obtained from the SSTS at Baseline.
6. Montgomery-Åsberg Depression Rating Scale (MADRS) score >28 at Screening and
before randomization on Day 1.
7. Participants must agree to receive pharmacological standard of care
treatment to treat their MDD (as determined by the treating physician(s) based
on clinical judgement and local treatment guidelines) during the trial
duration.
8. In the physician's opinion, acute psychiatric hospitalization is clinically
warranted to treat the patient*s condition, and the patient is either already
in the hospital or agrees to be hospitalized voluntarily for the required per
protocol period.
Exclusion criteria
1. Any prior or current diagnosis of bipolar disorder, MDD with psychotic
features, schizophrenia, or schizoaffective disorder as obtained from M.I.N.I.
at Screening
2. Patients with acute alcohol or substance use disorder or withdrawal symptoms
requiring detoxification, or patients who went through detoxification treatment
(inpatient or outpatient) within 1 month before Screening.
3. Participant has a current clinical diagnosis of autism, dementia, or
intellectual disability
4. History of seizures. Note: childhood febrile seizures are not exclusionary
5. Participants with borderline personality disorder as obtained from M.I.N.I.
at Screening.
6. Participants with suicidal ideation or behavior caused primarily by another
non-MDD condition as obtained from M.I.N.I. at Screening
7.Known worsening or new appearance of suicidal ideation or behavior during a
prior
treatment with ketamine or esketamine or within 2 months after last ketamine or
esketamine
administration
8. Participants taking medications prohibited by the protocol
9. Intake of the following medications/ psychotherapy:
a. Esketamine or Ketamine 2 months before Screening
b. Monoamine oxidase inhibitors (MAOIs) 14 days before Screening
10. Any other condition (e.g. known liver disease/liver dysfunction, active
malignancy, etc.) which in the opinion of the investigator would put the safety
of the participant at risk, impede compliance or hinder completion of the
study.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | CMIJ821A12201 |
| EudraCT | EUCTR2020-003720-16-NL |
| CCMO | NL75939.100.21 |