ANAVEX3-71 for Schizophrenia

(SZ-001 Trial)

Overseen By James Tran

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Anavex Life Sciences Corp.

Must be taking: Atypical antipsychotics

Must not be taking: Clozapine, Daytime quetiapine

Disqualifiers: Pregnancy, Suicidal risk, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ANAVEX3-71 for individuals with schizophrenia. The goal is to assess the treatment's safety, effectiveness, and impact on the body. The trial includes different groups trying various doses, along with some groups receiving a placebo (a substance with no active medication) for comparison. Suitable candidates have had a schizophrenia diagnosis for at least a year and exhibit stable symptoms that have not changed significantly recently. Participants must maintain a steady medication plan without clozapine and have a safe, consistent living situation. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You will need to stay on your current antipsychotic medications if they are second-generation types, except for clozapine, which is not allowed. You can use quetiapine for sleep at doses less than 300 mg, but not during the day.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ANAVEX3-71 is safe and well-tolerated by people with schizophrenia. Recent studies found no major safety issues, and the treatment was generally safe. Both men and women handled the treatment well, indicating it is safe for many patients. While this is encouraging, discussing potential risks with a healthcare provider before joining a clinical trial is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Schizophrenia?

Researchers are excited about ANAVEX3-71 for schizophrenia because it represents a new approach to treating the condition. Unlike standard treatments such as antipsychotics, which primarily target dopamine receptors, ANAVEX3-71 operates through sigma-1 receptor modulation. This mechanism could potentially address symptoms with fewer side effects. Additionally, ANAVEX3-71 may offer improved cognitive benefits, which is a significant challenge in existing therapies for schizophrenia.

What evidence suggests that ANAVEX3-71 might be an effective treatment for Schizophrenia?

Research shows that ANAVEX3-71 may help treat schizophrenia. Previous studies found that this treatment is safe and well-tolerated by adults with the condition. In this trial, participants will join different arms, including those receiving ANAVEX3-71 at varying doses and those receiving a placebo. In a study where some patients received a placebo (a harmless pill with no effect), ANAVEX3-71 achieved its main goal by showing positive results in patients already taking stable antipsychotic medication. These findings suggest that ANAVEX3-71 could help manage schizophrenia symptoms when used with existing treatments. However, more research is needed to confirm these results and determine the best dosage. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

Adults aged 18-50 with stable schizophrenia, on consistent antipsychotic medication for at least 6 weeks, and a BMI between 18.5 to 40 kg/m2 can join this trial. They must have a specific cognition score, not be drug or alcohol users, and agree to stay inpatient as required. Pregnant individuals or those with recent investigational drug use are excluded.

Inclusion Criteria

Has a negative urine screen for drugs of abuse and negative alcohol breath test at screening and check-in

I have been diagnosed with schizophrenia for at least 1 year.

My schizophrenia symptoms have been stable for at least 6 weeks.

Exclusion Criteria

Simpson Angus Scale (SAS) total score ≥5 at the screening and baseline visits

Risk for suicidal behavior during the study

I have not been diagnosed with a mental health disorder other than schizophrenia in the past year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A: Multiple Ascending Dose

Participants receive multiple ascending doses of ANAVEX3-71 for dose selection, safety, and pharmacokinetics assessment

10 days

In-patient study

Part B: Double-Blind, Placebo-Controlled

Participants receive either ANAVEX3-71 or placebo to assess exploratory efficacy and continued repeat-dose safety

28 days

In-patient study

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ANAVEX3-71

Trial Overview The study is testing ANAVEX3-71 oral capsules against placebo to assess their safety and effectiveness in treating schizophrenia symptoms. It also looks into how the body processes the drug and its effects on brain function.

How Is the Trial Designed?

Group I: ANAVEX3-71 30 mg TID (Part A) Active Control 1 Intervention

The first active treatment arm of the study during Part A (multiple ascending doses).

Group II: ANAVEX3-71 60 mg TID (Part A) Active Control 1 Intervention

The second active treatment arm of the study during Part A (multiple ascending doses).

Group III: ANAVEX3-71 TBD mg TID (Part B) Active Control 1 Intervention

The active arm of Part B of the study. The dose will be determined based on data obtained in Part A.

Group IV: ANAVEX3-71 Placebo TID (Part A) Placebo Group 1 Intervention

The placebo arm of Part A (multiple ascending doses).

Group V: ANAVEX3-71 Placebo TID (Part B) Placebo Group 1 Intervention

The placebo arm of Part B of the study.

Who Is Running the Clinical Trial?

Anavex Life Sciences Corp.

Lead Sponsor

Trials

13

Recruited

1,600+

Hassman Research Institute

Collaborator

Trials

1

Recruited

40+

Cognitive Research Corporation

Industry Sponsor

Trials

25

Recruited

2,400+

COGNISION

Collaborator

Trials

3

Recruited

230+

Published Research Related to This Trial

The study highlights that the alpha7-nicotinic acetylcholine receptor is less expressed in certain brain areas of schizophrenia patients, which may contribute to sensory inhibition deficits and eye movement issues associated with the disorder.

Anabasine, a selective alpha7-nicotinic acetylcholine receptor agonist, was found to reduce MK-801-induced popping behavior in mice without causing seizures, suggesting its potential as a therapeutic option for schizophrenia while also noting the need to monitor for seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anabasine, a selective nicotinic acetylcholine receptor agonist, antagonizes MK-801-elicited mouse popping behavior, an animal model of schizophrenia. Mastropaolo, J., Rosse, RB., Deutsch, SI.[2013]

The study found that DMXB, an alpha(7) nicotinic agonist, significantly improved auditory gating deficits in rats that were socially isolated after weaning, indicating its potential efficacy for similar conditions in schizophrenia.

In contrast, control rats showed impaired auditory gating at higher doses of DMXB, suggesting that while DMXB can help certain deficits, it may have adverse effects at elevated doses in healthy subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DMXB, an alpha7 nicotinic agonist, normalizes auditory gating in isolation-reared rats. O'Neill, HC., Rieger, K., Kem, WR., et al.[2018]

In a Phase 2 study involving 16 patients with schizophrenia, DMXB-A, a partial agonist at α7 nicotinic acetylcholine receptors, significantly altered default network activity in the brain, suggesting potential therapeutic effects on brain function associated with schizophrenia.

The changes in brain activity, particularly a reduction in posterior cingulate activity, were influenced by the CHRNA7 genotype, indicating that the efficacy of DMXB-A may be mediated through the α7-nicotinic receptor, highlighting the role of nicotinic cholinergic dysfunction in schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of an alpha 7-nicotinic agonist on default network activity in schizophrenia. Tregellas, JR., Tanabe, J., Rojas, DC., et al.[2021]

In a study involving 16 patients with schizophrenia, the 150-mg dose of DMXB-A significantly reduced hippocampal activity during a smooth pursuit eye movement task, suggesting it effectively targets the intended alpha7-nicotinic acetylcholine receptors.

The 75-mg dose of DMXB-A did not show any significant effect, indicating that the drug's efficacy may depend on achieving a certain dosage, which is important for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional magnetic resonance imaging of effects of a nicotinic agonist in schizophrenia. Tregellas, JR., Olincy, A., Johnson, L., et al.[2021]

In a phase 2 trial involving 31 subjects with schizophrenia, DMXB-A, a partial alpha(7)-nicotinic agonist, showed significant improvement in negative symptoms, particularly anhedonia and alogia, compared to placebo.

While DMXB-A did not significantly enhance cognitive measures overall, it did show some positive effects on attention and working memory at higher doses, indicating potential benefits for treatment-resistant symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial phase 2 trial of a nicotinic agonist in schizophrenia. Freedman, R., Olincy, A., Buchanan, RW., et al.[2022]

Citations

1. anavex.com anavex.com/post/anavex-life-sciences-announces-positive-topline-results-from-phase-2-study-of-anavex-3-71-for-the-tr

Anavex Life Sciences Announces Positive Topline Results ... ANAVEX3-71-SZ-001 achieved its primary endpoint demonstrating safety and tolerability in adults with schizophrenia.

2. anavex.com anavex.com/post/anavex-life-sciences-announces-successful-development-of-once-daily-oral-tablet-formulation-for-the

Anavex Life Sciences Announces Successful ... ANAVEX3-71-002 trial achieved its primary endpoint demonstrating safety and tolerability in both male and female adults.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06245213

A Study of ANAVEX3-71 in Adults With Schizophrenia A study to evaluate the safety, tolerability, efficacy, pharmacokinetics, and electrophysiology of ANAVEX3-71 in patients with Schizophrenia.

4. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/anavex-drug-delivers-positive-phase-2-schizophrenia-results/

Anavex Drug Delivers Positive Phase 2 Schizophrenia ... ANAVEX3-71 met its primary endpoint in a placebo-controlled Phase 2 study in adults with schizophrenia on stable antipsychotic therapy, ...

5. anavex.com anavex.com/post/anavex-life-sciences-announces-full-enrollment-of-phase-2-study-of-anavex-3-71-for-the-treatment-of

Anavex Life Sciences Announces Full Enrollment of Phase ... Anavex Life Sciences Announces Full Enrollment of Phase 2 Study of ANAVEX®3-71 for the Treatment of Schizophrenia.

6. msn.com msn.com/en-us/money/general/anavex-rises-after-trial-data-for-schizophrenia-candidate-update/ar-AA1NJnQD?apiversion=v2&domshim=1&noservercache=1&noservertelemetry=1&batchservertelemetry=1&renderwebcomponents=1&wcseo=1

Anavex rises after trial data for schizophrenia candidate ... Citing topline data, Anavex (NASDAQ:AVXL) announced that ANAVEX 3-71 was found to be safe and well-tolerated in the placebo-controlled Phase 2 clinical study, ...