Evaluating Gonyautoxins for Chemotherapy-Induced Peripheral Neuropathy

Proof of Principle Study Evaluating the Effects of Gonyautoxins, Paralytic Shellfish Poisoning (PSP) NEURO SERUM, on Objective and Subjective Symptoms of Chemotherapy-induced Peripheral Neuropathy (CINP)

This study is testing if a new treatment called gonyautoxins can help people with nerve pain from chemotherapy feel better and improve their sensitivity to touch.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Algenis SpA (industry)
• Drugs / interventions: chemotherapy
• Locations: 9 sites (Salvador, Bahia and 8 other locations)
• Trial ID: NCT05052398 on ClinicalTrials.gov

What this trial studies

This proof-of-concept study assesses the effects of gonyautoxins (PSP NEURO SERUM) on safety and tactile sensitivity in patients suffering from chemotherapy-induced peripheral neuropathy (CIPN) due to solid tumors. The study is divided into two parts: the first part evaluates the activity and tolerability of the treatment, while the second part involves a randomized comparison of PSP NEURO SERUM versus a placebo. Patients will receive the investigational treatment three times a day for 28 days, with the primary objective being to measure tactile sensation and safety. The study will only proceed to the second part if sufficient responses are observed in the first part.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with solid tumors who have developed grade 2 or higher peripheral sensory neuropathy due to chemotherapy.

Not a fit: Patients who do not have chemotherapy-induced peripheral neuropathy or those with neuropathy caused by other factors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve tactile sensitivity and quality of life for patients suffering from CIPN.

How similar studies have performed: While this approach is novel, similar studies targeting CIPN have shown varying degrees of success, indicating potential but uncertain outcomes.

Eligibility criteria

Inclusion Criteria:

1. Written informed consent
2. Age ≥18 years
3. Histological diagnosis of cancer (hematologic or solid tumors).
4. Part 1: Treatment with antineoplastic agents that induce peripheral neuropathy in neoadjuvant, adjuvant, or metastatic scenario; Part 2: Treatment with taxanes peripheral neuropathy inducers in the neoadjuvant, adjuvant, or metastatic scenario.
5. Peripheral sensory neuropathy grade 2 or higher on upper limbs as per NCI-CTCAE v5.0. and with alteration of the Semmes Weinstein monofilament test.
6. Part 1: Diagnosis of peripheral sensory neuropathy during treatment with antineoplastic agents drugs that induce peripheral neuropathy or up to 2 weeks after the last chemotherapy infusion; Part 2: Diagnosis of peripheral sensory neuropathy during treatment with peripheral neuropathy-inducing taxanes or up to 2 weeks after last chemotherapy infusion.
7. Part 1: Patients with chronic symptoms related to peripheral sensory neuropathy who have completed treatment with peripheral neuropathy-inducing antineoplastic agents for more than 2 weeks and without any exclusion criteria, may be included. Part 2: Patients with chronic symptoms related to sensory peripheral neuropathy who completed treatment with peripheral neuropathy-inducing taxanes for more than 2 weeks and no exclusion criteria, can be included.
8. Patients using neuropathic pain modulators will be allowed if there is no dose adjustments in the last 2 weeks and if sensory symptoms persist related to CIPN, or if the use is for another indication.
9. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
10. Documented willingness to use an effective contraceptive method while participate in the study for male patients with partners or female participants with the potential to become pregnant.
11. Part 1: Hand skin and cuticles must be intact. Part 2: Skin of hands, feet and cuticles must be intact.

Exclusion Criteria:

1. Prior treatment with gonyautoxins or any small molecule neurotoxins.
2. Female participants who are pregnant (positive urine pregnancy test), who have an infant they are breastfeeding, or intend to become pregnant within 3 months.
3. History of peripheral sensory neuropathy attributed to any cause other than chemotherapy.
4. Patients receiving systemic treatment that has among its common side effects (\> 1%) peripheral neuropathy, or who have received the same within the last 2 weeks. The use during the study of systemic drugs such as hormone therapy (e.g. tamoxifen, aromatase inhibitor, etc), or other agents that do not have among their common side effects (\>1%) peripheral neuropathy, will be allowed.
5. Patients with grade 2 CIPN with perceived improvement of symptoms.
6. Changes in neuropathic pain modulators will not be allowed.
7. Any other therapies for chemotherapy-induced peripheral neuropathy must be discontinued at least 2 weeks before the first dose of study drug.
8. Known hypersensitivity reaction to PSP Neuro serum.
9. Patients with a known or suspected shellfish allergy.
10. No dermatologic lesions on hands and feet and cuticles that might increase systemic exposure of the investigational medicinal product (IMP).
11. Distal muscle weakness and/or atrophy.
12. History of alcoholism or alcohol intake of 168g (21 units) for men and 112g (14 units) for women per week on a regular basis (time \> 3 months). 1 unit = 10mL = 8g of pure alcohol.
13. Clinically significant abnormalities of glucose metabolism as defined by any of the following:

    1. Diagnosis of type I or II diabetes mellitus (regardless of management) that have symptoms attributable to diabetic neuropathy pre-treatment with chemotherapy. Well-controlled diabetic patients (regardless of management), previously asymptomatic may be included.
    2. Glycosylated hemoglobin (HbA1C) ≥8.0% at screening.
    3. Fasting serum glucose ≥ 160 mg/dL at screening. Fasting is defined as no caloric intake for at least 8 hours.
14. Vitamin B12 deficiency defined as \< 250 ng/mL.
15. Phosphate levels above upper limit of normal (ULN).
16. ECG: QTc interval (Fridericia Formula) ≥ 450ms.
17. Positive Tinel and/or Phalen test.
18. Participation in another clinical trial and any concurrent treatment with any investigational drug within 4 weeks prior to trial entry / randomization.
19. Surgery, radiotherapy, or systemic therapy that in the investigators' opinion might interfere/ worsen symptoms and the evaluation of peripheral neuropathy within 2 weeks prior to trial entry /randomization.
20. Any other finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patients at high risk from treatment complications.
21. Unresolved clinically significant toxicity from prior therapy except for alopecia.
22. Failure to adhere to study treatment and follow-up procedures.

Where this trial is running

Salvador, Bahia and 8 other locations

• Nucleo de Oncologia da Bahia — Salvador, Bahia, Brazil (RECRUITING)
• Oncoclínicas Vitória — Vitória, Espírito Santo, Brazil (RECRUITING)
• Oncoclinicas do Brasil Servicios Medicos SA — Belo Horizonte, Minas Gerais, Brazil (RECRUITING)
• Centro Oncológico do Triângulo S.A. — Uberlândia, Minas Gerais, Brazil (RECRUITING)
• Oncoclínicas João Pessoa — João Pessoa, Paraíba, Brazil (RECRUITING)
• Multihemo — Recife, Pernambuco, Brazil (RECRUITING)
• Oncoclínicas Florianópolis — Florianópolis, Santa Catarina, Brazil (RECRUITING)
• Oncoclinicas Rio de Janeiro SA — Rio de Janeiro, Brazil (RECRUITING)
• Centro de Paulista de Oncologia — Sao Paulo, Brazil (RECRUITING)

Study contacts

• Principal investigator: Mariane Fontes, MD — Oncoclínicas
• Study coordinator: Mariane Fontes, MD

Conditions: Chemotherapy-induced Peripheral Neuropathy