Clinical trial NCT06245213: A Study of ANAVEX3-71 in Adults With Schizophrenia
Official title: A Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Electrophysiology of ANAVEX3-71 in Adult Patients With Schizophrenia in a Multiple Ascending Dose Study (Part A), Followed by a Double-Blind, Randomized, Placebo-Controlled Study (Part B)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Schizophrenia
Keywords: Schizophrenia
EEG
Multiple Ascending Dose
Interventional
Sigma-1 Receptor Agonist
M1 Muscarinic Receptor Agonist
Biomarkers
Pharmacokinetics
Pharmacodynamics
Lead sponsor: Anavex Life Sciences Corp.
Sponsor class: INDUSTRY
Collaborators: name: COGNISION
name: Cognitive Research Corporation
name: Hassman Research Institute
First posted: 2024-02-07
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment in Part A and Part B. Part A: n = 16; Part B: n = 55;
Primary purpose: TREATMENT

Brief summary: A study to evaluate the safety, tolerability, efficacy, pharmacokinetics, and electrophysiology of ANAVEX3-71 in patients with Schizophrenia.

Detailed description: ANAVEX3-71-SZ-001 is a two-part study. The first part is Part A: Multiple Ascending Dose, PK, safety, and dose selection. The second part is Part B: Double Blind, Placebo Controlled for exploratory efficacy and continued repeat-dose safety. This study will investigate the effects of ANAVEX3-71 in patients with Schizophrenia for the first time. This is an in-patient study. In both parts, participants will undergo either 10 or 28 days of dosing (Part A and Part B, respectively). Standard clinical outcome measures used in the clinic and novel fluid and electrophysiological biomarkers will also be assessed.

Eligibility criteria: Inclusion Criteria:

1. Male and female volunteers 18-55 years of age, inclusive at screening.
2. Has a primary diagnosis of schizophrenia, for ≥ 1 year
3. Stable schizophrenia psychiatric symptoms for at least 6 weeks prior to screening.
4. Schizophrenia clinical symptom severity defined by meeting ALL of the following per the Positive and Negative Syndrome Scale (PANSS) item scores at screening:

   1. Delusions (P1) ≤ 4
   2. Hallucinatory behavior (P3) ≤ 4
   3. Unusual thought content (G9) ≤ 4
   4. Hostility (P7) ≤ 4
5. Patient has a PANSS total score ≤ 80 at screening and baseline visits and no worsening in PANSS total score between screening and baseline, of more than 20%.
6. Has a Brief Assessment of Cognition (BACS) T-score \< 50 at the screening visit.
7. On a stable regimen of at least one and up to a maximum of two second-generation ("atypical") antipsychotic medications for at least 6 weeks prior to screening and agree to stay on this regimen for their entire study participation, with the following exceptions:

   1. Clozapine use is not permitted
   2. Quetiapine for sleep at doses less than 300 mg are permitted.
   3. Day time (including morning) quetiapine use as the background antipsychotic is not permitted.
8. Able to understand the requirements of the study and able and willing to provide written informed consent and to abide by the study procedures, in the judgment of the Investigator, including able and willing to remain in an in-patient setting during the study.
9. If of childbearing potential, using adequate contraceptive methods for the duration of the study.
10. Body mass index of 18.5 to 40.0 kg/m2 (inclusive) and total body weight \> 50 kg (110 lbs.) for males and \> 40 kg (88 lbs.) for females.
11. Has a negative urine screen for drugs of abuse and negative alcohol breath test at screening and check-in.
12. Patient resides in a stable living situation and is anticipated to return to that same stable living situation.

Exclusion Criteria:

1. Participation in a schizophrenia study in which the patient has received any investigational medications within 60 days prior to the baseline visit.
2. History or presence of a clinically significant, poorly treated, or unstable conditions that would jeopardize the safety of the patient or the validity of the study results.
3. Clinically significant abnormal findings on the physical examination, medical history, ECG, or clinical laboratory results at screening.
4. Calgary Depression Scale for schizophrenia (CDSS) score ≥6 at the screening or baseline visits.
5. Simpson Angus Scale (SAS) total score ≥5 at the screening and baseline visits at the screening or baseline visits.
6. Abnormal Involuntary Movement (AIMS) score of 2 for two or more movements or a score of 3 or 4 for any single movement on this scale at the screening or baseline visits.
7. Any primary the DSM-5-TR (American Psychiatric Association 2022) disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening).
8. Pregnant, lactating, or less than 3 months postpartum. Sperm donation is not allowed for 90 days after the final dose of study drug.
9. Risk for suicidal behavior during the study.
10. Inability to detect a 1000 Hz tone at 40 dB in both ears at screening.
11. Has psychiatric hospitalization(s) for more than 30 days (cumulative) during the 90 days before screening.

Primary outcomes:
measure: Single Dose Maximum Observed Plasma Concentration (Cmax)
timeFrame: Part A: Day 1
measure: Multiple Dose Maximum Observed Plasma Concentration (Cmax)
timeFrame: Part A: Day 1 and Day 9
measure: Cmax (steady state)
timeFrame: Part A: Day 1 and Day 9
measure: Tmax (steady state)
timeFrame: Part A: Day 1 and Day 9
measure: AUC (steady state)
timeFrame: Part A: Day 1 and Day 9
measure: AUC (single state)
timeFrame: Part A: Day 1 and Day 9
measure: CL/F (steady state)
timeFrame: Part A: Day 1 and Day 9
measure: Vz/F (steady state)
timeFrame: Part A: Day 1 and Day 9
measure: T1/2 (steady state)
timeFrame: Part A: Day 1 and Day 9
measure: Rac (steady state)
timeFrame: Part A: Day 1 and Day 9
measure: Rac, Cmax (steady state)
timeFrame: Part A: Day 1 and Day 9
measure: PTR (steady state)
timeFrame: Part A: Day 1 and Day 9
measure: Adverse Events
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: Vital Signs
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: 12-lead ECG (RR interval)
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: 12-lead ECG (P wave)
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: 12-lead ECG (PR interval)
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: 12-lead ECG (PR segment)
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: 12-lead ECG (QRS complex)
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: 12-lead ECG (ST segment)
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: 12-lead ECG (T wave)
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: 12-lead ECG (QT interval)
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: Clinical Safety Labs - Renal Panel
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: Clinical Safety Labs - Hepatic Panel
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: Clinical Safety Labs - Lipid Panel
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: Clinical Safety Labs - Hematology Panel
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: Clinical Safety Labs - Urinalysis Panel
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: Clinical Safety Labs - Coagulation Panel
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: Brief Physical Examination
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: Brief Neurological Examination
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: AIMS
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: SAS
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: BARS
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: CDSS
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: C-SSRS
timeFrame: Part A and Part B Screening to Safety Follow Up Visit; Up to 78 days (Part A) and Up to 114 days (Part B)
measure: EEG-ERP - Passive, Duration Deviant, Oddball ERP
timeFrame: Part A and Part B: Up to 12 days (Part A) and Up to 30 days (PartB)
measure: EEG-ERP - Active, Auditory, Oddball ERP
timeFrame: Part A and Part B: Up to 12 days (Part A) and Up to 30 days (PartB)
measure: EEG-ERP - Auditory Steady State Response
timeFrame: Part A and Part B: Up to 12 days (Part A) and Up to 30 days (PartB)
measure: EEG-ERP - Resting EEG
timeFrame: Part A and Part B: Up to 12 days (Part A) and Up to 30 days (PartB)
Secondary outcomes:
measure: Positive and Negative Syndrome Scale (PANSS)
timeFrame: Part A and Part B: Up to 12 days (Part A) and Up to 30 days (PartB)
measure: Brief Assessment of Cognition in Schizophrenia (BACS)
timeFrame: Part A and Part B: Up to 12 days (Part A) and Up to 30 days (PartB)
measure: Clinical Global Impressions Scale Schizophrenia (CGI-SCH)
timeFrame: Part A and Part B: Up to 12 days (Part A) and Up to 30 days (PartB)
measure: Virtual Reality Functional Capacity Assessment Tool (VRFCAT)
timeFrame: Part A and Part B: Up to 12 days (Part A) and Up to 30 days (PartB)
measure: Blood measurements of chitinase-3-like protein 1 (YKL-40)
timeFrame: Part B: Baseline to End of Treatment (Day -2 to Day 28)
measure: Blood measurements of glial fibrillary acidic protein (GFAP)
timeFrame: Part B: Baseline to End of Treatment (Day -2 to Day 28)
measure: Blood measurements of circulating amino acid metabolites
timeFrame: Part B: Baseline to End of Treatment (Day -2 to Day 28)
measure: Exploratory DNA/RNA, including whole genome analysis and whole transcriptome mRNA
timeFrame: Part B: Baseline to End of Treatment (Day -2 to Day 28)
Other outcomes:
Locations:
city: Marlton
country: United States
facility: CenExel Hassman Research Institute
state: New Jersey
Study officials:
References: