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

71 Participants Needed

Trial Summary

What is the purpose of this trial?

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

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.

How is the drug ANAVEX3-71 different from other schizophrenia treatments?

ANAVEX3-71 is unique because it targets alpha7-nicotinic acetylcholine receptors, which are often deficient in people with schizophrenia. This mechanism may help improve cognitive and sensory processing deficits associated with the condition, offering a novel approach compared to traditional antipsychotics. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effects of an alpha 7-nicotinic agonist on default network activity in schizophrenia. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

DMXB, an alpha7 nicotinic agonist, normalizes auditory gating in isolation-reared rats. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Functional magnetic resonance imaging of effects of a nicotinic agonist in schizophrenia. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

Initial phase 2 trial of a nicotinic agonist in schizophrenia. [2022]