SPG601 for Fragile X Syndrome

Overseen By Sarah Richter

Age: 18 - 65

Sex: Male

Trial Phase: Phase 2

Sponsor: Spinogenix

Must be taking: Psychotropic drugs

Disqualifiers: Uncontrolled seizures, Epilepsy, Substance abuse, others

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

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SPG601 for Fragile X syndrome, a genetic condition affecting learning and behavior. The goal is to determine if SPG601 is safe and effective for managing symptoms in adult men with this condition. Participants will receive either the SPG601 treatment or a placebo (a harmless pill resembling the real medicine) to compare results. Men confirmed to have Fragile X syndrome through genetic testing and who are in good health might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications?

The trial requires that you have stable dosing of psychotropic drugs for at least 4 weeks before participating. Other medications are not specifically mentioned, so the protocol does not specify if you need to stop taking them.

Is there any evidence suggesting that SPG601 is likely to be safe for humans?

Research has shown that SPG601 appears safe for adult men with Fragile X syndrome. Participants in these studies handled the treatment well, with no reports of serious side effects linked to SPG601. The FDA has also granted the drug special recognition, such as Orphan Drug and Fast Track status, often indicating confidence in its safety. Although all details on side effects are not yet available, current evidence suggests that SPG601 is generally well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Fragile X Syndrome, which often include medications like antipsychotics or stimulants to manage symptoms, SPG601 offers a fresh approach by targeting the underlying mechanisms of the condition. Researchers are excited about SPG601 because it has the potential to directly influence the neural pathways associated with Fragile X Syndrome, rather than just addressing the symptoms. This targeted approach might provide more significant improvements and faster results, offering hope for patients who haven't seen much success with existing options.

What evidence suggests that SPG601 might be an effective treatment for Fragile X Syndrome?

Studies have shown that SPG601 may help people with Fragile X syndrome by calming unusual brain activity. In earlier trials, SPG601 improved brain function, thinking, and memory skills in adult men with this condition. This trial will compare SPG601 with a placebo to evaluate its effectiveness. SPG601 has shown strong signs of effectively addressing symptoms. The FDA has recognized its potential by granting it special designations, highlighting its promise for treating Fragile X syndrome. Overall, early findings suggest that SPG601 could effectively manage symptoms of this condition. ^{1 5 6 7 8}

Who Is on the Research Team?

Craig Erickson, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

Adult men aged 18-45 with Fragile X Syndrome can join this trial if they're in good health, have stable use of psychotropic drugs for at least a month, and are using contraception. They need a caregiver and confirmed diagnosis via genetic testing. Those with uncontrolled seizures, recent substance abuse, or conditions affecting study completion cannot participate.

Inclusion Criteria

I am a man aged between 18 and 45.

Able and willing to provide written informed consent

I am in good health with no major medical issues.

Exclusion Criteria

Any physical or psychological condition that prohibits study completion

Auditory or visual impairments that cannot be corrected

History of suicidal behavior or suicidal ideation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single oral dose of SPG601 or placebo at the first visit and cross over to receive the other product at the second visit

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• SPG601

Trial Overview The trial is testing SPG601's safety and effectiveness compared to a placebo in treating adult men with Fragile X Syndrome. It will also look into how the body processes the drug and its impact on the body's functions.

How Is the Trial Designed?

Group I: Experimental: Active SPG601 to be administered to participants with Fragile X Syndrome Active Control 1 Intervention

Participants with Fragile X Syndrome will be randomized to receive SPG601 or placebo (8 capsules of 100 mg) one time on days 1 and 8 of the study.

Group II: Placebo Comparator: Placebo comparator to be administered to participants with Fragile X Syndrome Placebo Group 1 Intervention

Participants with Fragile X Syndrome will be randomized to receive SPG601 or placebo (8 capsules of 100 mg) one time on days 1 and 8 of the study.

Who Is Running the Clinical Trial?

Spinogenix

Lead Sponsor

Trials

6

Recruited

220+

Avance Clinical Pty Ltd.

Industry Sponsor

Trials

23

Recruited

3,700+

Published Research Related to This Trial

Fragile X syndrome (FXS) is caused by the absence of the FMRP protein, leading to excessive translation of neuronal proteins, which disrupts synaptic plasticity and contributes to intellectual disability and autism.

Recent research indicates that the lack of FMRP also causes imbalances in diacylglycerol (DAG) and phosphatidic acid (PA) levels, which are crucial for various cellular processes and may serve as new therapeutic targets for treating FXS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fragile X syndrome: Are signaling lipids the missing culprits? Tabet, R., Vitale, N., Moine, H.[2017]

NNZ-2566, a synthetic analog of IGF-1, showed promise in correcting various symptoms of Fragile X syndrome in fmr1 knockout mice, including learning and memory deficits, hyperactivity, and social interaction issues.

The study suggests that targeting the IGF-1 molecular pathway may be a novel and effective approach for treating Fragile X syndrome, with a clinical trial currently underway to evaluate its effects in human patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NNZ-2566, a novel analog of (1-3) IGF-1, as a potential therapeutic agent for fragile X syndrome. Deacon, RM., Glass, L., Snape, M., et al.[2018]

Fragile X syndrome (FXS) is the most common genetic cause of intellectual disability and autism spectrum disorder, primarily caused by the expansion of CGG repeats in the FMR1 gene.

Molecular genetic testing of the FMR1 gene can guide early treatment and prevention strategies for families affected by FXS, helping to standardize diagnosis and care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical practice guidelines for Fragile X syndrome]. Clinical Genetics Group Of Medical Geneticist Branch Of Chinese Medical Doctor Association, ., Clinical Genetics Group Of Medical Genetics Branch Of Chinese Medical Association, ., Genetic Disease Prevention And Control Group Of Professional Committee For Birth Defect Prevention And Control Of Chinese Preventive Medicine Association, ., et al.[2022]

In two phase 2b clinical trials involving 175 adults and 139 adolescents with Fragile X syndrome, the mGluR5 antagonist mavoglurant did not show significant improvement in behavioral symptoms after 12 weeks of treatment, failing to confirm previous findings.

The safety profile of mavoglurant was consistent with earlier studies, showing few adverse events, but the trials indicated that the methylation status of the FMR1 gene did not predict treatment efficacy, suggesting a need for further research in younger populations and with different assessment markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials. Berry-Kravis, E., Des Portes, V., Hagerman, R., et al.[2016]

A novel short chain fatty acid derivative, sodium 2,2 dimethylbutyrate (SDMB), was well-tolerated in healthy adults with no significant adverse events, suggesting it is a safe option for further study.

In a 14-day trial, SDMB increased reticulocyte levels at all tested doses, indicating its potential efficacy in boosting fetal hemoglobin production, which could benefit patients with beta hemoglobinopathies like sickle cell disease and beta thalassemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of safety and pharmacokinetics of sodium 2,2 dimethylbutyrate, a novel short chain fatty acid derivative, in a phase 1, double-blind, placebo-controlled, single-dose, and repeat-dose studies in healthy volunteers. Perrine, SP., Wargin, WA., Boosalis, MS., et al.[2021]

A 1-year-old infant with nonketotic hyperglycinemia (NKH) showed significant clinical improvement, including resolution of nystagmus and better developmental milestones, after adding low-dose dextromethorphan (0.25 mg/kg per day) to their treatment regimen.

This case suggests that low-dose dextromethorphan may be effective in managing symptoms of NKH, even at doses much lower than previously studied, indicating a need for further research on its safety and efficacy in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of low-dose dextromethorphan in the treatment of nonketotic hyperglycinemia. Alemzadeh, R., Gammeltoft, K., Matteson, K.[2013]

Using an animal model of Fragile X syndrome, researchers found that certain FDA-approved psychoactive drugs can enhance cognitive performance by activating specific serotonin and dopamine receptors, leading to improved signaling and synaptic plasticity.

Combining these drugs at low doses not only restored normal learning in the model without causing anxiety-related side effects but also suggests a potential new treatment strategy for cognitive impairments in Fragile X syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological rescue of Ras signaling, GluA1-dependent synaptic plasticity, and learning deficits in a fragile X model. Lim, CS., Hoang, ET., Viar, KE., et al.[2021]

eFT508, a specific MNK inhibitor, shows promise in treating Fragile X syndrome (FXS) by reducing the phosphorylation of eIF4E, which is linked to cognitive and behavioral deficits in FXS.

In mouse models, eFT508 successfully alleviated various FXS-related issues, including behavioral deficits and physical abnormalities, suggesting it could be a viable therapeutic option for reversing symptoms of FXS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Highly Selective MNK Inhibitor Rescues Deficits Associated with Fragile X Syndrome in Mice. Shukla, T., de la Peña, JB., Perish, JM., et al.[2023]

Pharmacologic activation of the GABA(B) receptor using STX209 (arbaclofen) successfully corrected elevated protein synthesis and synaptic abnormalities in a mouse model of Fragile X syndrome, indicating its potential as a therapeutic intervention.

Chronic administration of STX209 in juvenile Fmr1-knockout mice reduced excessive dendritic spine density without affecting normal spine density in wild-type mice, suggesting a targeted effect on the pathological features of Fragile X syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABAB receptors with arbaclofen. Henderson, C., Wijetunge, L., Kinoshita, MN., et al.[2022]

In a study involving Sprague-Dawley rats, ST-20 (sodium 2,2-dimethylbutyrate) showed a no-observed adverse effect level of 200 mg/kg, indicating it is relatively safe at this dosage for up to 15 days of administration.

At higher doses (1,000 mg/kg), ST-20 caused significant toxic effects, including ataxia, decreased body weights, and changes in blood parameters, but these effects were fully reversible after a 14-day recovery period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term toxicity study of ST-20 (NSC-741804) by oral gavage in Sprague-Dawley rats. Terse, PS., Johnson, JD., Hawk, MA., et al.[2017]

In a study involving 8 children with hemoglobin SS (HbSS), low doses of oral sodium phenylbutyrate (SPB) successfully increased F-reticulocytes, indicating enhanced hemoglobin F (HbF) synthesis, with statistical significance (P = 0.002).

Among the patients who continued treatment for over 10 weeks, 3 out of 5 showed substantial increases in HbF levels, suggesting that lower doses of SPB can be effective in promoting HbF synthesis in children with HbSS, warranting further research to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of fetal hemoglobin synthesis in children with sickle cell anemia on low-dose oral sodium phenylbutyrate therapy. Resar, LM., Segal, JB., Fitzpatric, LK., et al.[2019]

In a phase II study involving 76 subjects with sickle cell disease, HQK-1001 showed a minimal increase in fetal hemoglobin (Hb F) levels compared to placebo, with only 24% of patients experiencing an increase greater than 3%.

The study also indicated a concerning trend of increased pain crises in the HQK-1001 group, with an average of 3.5 crises per year compared to 1.7 in the placebo group, leading to the conclusion that further daily administration of HQK-1001 is not recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled phase II study of the efficacy and safety of 2,2-dimethylbutyrate (HQK-1001), an oral fetal globin inducer, in sickle cell disease. Reid, ME., El Beshlawy, A., Inati, A., et al.[2022]

Citations

1. spinogenix.com spinogenix.com/spinogenix-completes-phase-2-study-of-spg601-fortreatment-offragile-x-syndrome-a-common-inherited-form-of-autismshowing-strong-efficacy-signal-in-measures-of-abnormal-brain-activity/

Spinogenix Completes Phase 2 Study of SPG601 for ... Spinogenix completes Phase 2 study of SPG601 for treatment of Fragile X syndrome, a common inherited form of autism, showing strong efficacy signal.

2. prnewswire.com prnewswire.com/news-releases/spinogenix-announces-positive-type-c-meeting-with-the-fda-for-spg601-in-patients-with-fragile-x-syndrome-fxs-302543653.html

Spinogenix Announces Positive Type C Meeting with the ... SPG601 has received both Orphan Drug designation and Fast Track designation from the FDA for FXS, as well as orphan disease designation from the ...

3. synapse.patsnap.com synapse.patsnap.com/drug/f524aa36e5dd49c397ff9c0f10af52bd

SPG-601 - Drug Targets, Indications, Patents A Phase 2a, Randomized, Double-Blinded, Study Evaluating the Neurophysiologic vs Clinical Effects of Single-Dose SPG601 and Placebo in Adult Men With Fragile X ...

4. fragilexnewstoday.com fragilexnewstoday.com/news/spg601-calms-brain-activity-men-fxs-helping-focus/

SPG601 calms brain activity in men with FXS, helping them ... Treatment with Spinogenix's SPG601 showed promising results for men with fragile X syndrome (FXS) in a Phase 2a clinical trial.

5. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/spinogenix-receives-positive-fda-feedback-spg601-fragile-x-syndrome

Spinogenix Receives Positive FDA Feedback for SPG601 ... Phase IIa trial (NCT06413537) results show SPG601 improves neurophysiological and cognitive measures in patients with Fragile X syndrome.

6. spinogenix.com spinogenix.com/spinogenix-announces-positive-type-c-meeting-with-the-fda-for-spg601-in-patients-with-fragile-x-syndrome-fxs/

Spinogenix Announces Positive Type C Meeting with the ... SPG601 has received both Orphan Drug designation and Fast Track designation from the FDA for FXS, as well as orphan disease designation from the ...

7. go.drugbank.com go.drugbank.com/drugs/DB18742

SPG601: Uses, Interactions, Mechanism of Action Improve decision support & research outcomes with our structured adverse effects data. See a data sample. Toxicity. Not Available. Pathways: Not ...

8. prnewswire.com prnewswire.com/news-releases/spinogenix-to-present-complete-phase-2a-clinical-trial-results-for-spg601-a-first-in-class-fragile-x-syndrome-treatment-at-aacap-conference-302591334.html

Spinogenix to Present Complete Phase 2a Clinical Trial ... SPG601, Granted Fast Track Designation by the FDA, Reduced Signature Changes in High-Frequency Gamma Band Activity in Fragile X Syndrome ...