Eptinezumab for Diabetic Neuropathy

No longer recruiting at 2 trial locations

Overseen By Brenda A Nelson

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: CGRP antagonists, Opioids

Disqualifiers: Psychosis, Bipolar, Dementia, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called eptinezumab, a type of monoclonal antibody, to determine if it can reduce pain for people with diabetic neuropathy. Diabetic neuropathy occurs when high blood sugar damages nerves, causing pain, especially in the legs and feet. Participants will receive either eptinezumab or a placebo (a non-active treatment) to compare effects. Those who have experienced diabetic nerve pain for more than six months, particularly in their lower legs, may be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

Do I have to stop taking my current medications for the trial?

The trial does not require you to stop your current medications if they are stable doses of anticonvulsants, antidepressants, tramadol, or topical treatments (excluding high dose capsaicin patch and botulinum toxin type A). However, you cannot start new neuropathic pain medications like gabapentin, pregabalin, or certain antidepressants one month before or during the trial.

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

Previous studies have shown that eptinezumab is well-tolerated, with most people experiencing few side effects. Research indicates that those taking eptinezumab generally report minimal issues. The treatment is already approved for preventing migraines, suggesting it is relatively safe for humans. Although limited information exists on its safety for treating diabetic nerve damage, the existing approval for migraines provides some confidence in its safety. These findings should reassure those considering joining the trial. ^{1 2 3 4 5}

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

Eptinezumab is unique because it targets a protein called calcitonin gene-related peptide (CGRP), which is thought to play a role in pain signaling. Unlike standard treatments for diabetic neuropathy, which often include medications like pregabalin or duloxetine that work on different pathways, eptinezumab offers a new mechanism of action by blocking CGRP. Researchers are excited about eptinezumab because it is administered via infusion, which might provide longer-lasting relief from symptoms compared to daily oral medications. This new approach has the potential to improve the quality of life for those with diabetic neuropathy by offering a more targeted and possibly more effective treatment option.

What evidence suggests that eptinezumab might be an effective treatment for diabetic neuropathy?

Research shows that eptinezumab, a type of medication, may help reduce pain in people with diabetic neuropathy, a condition that causes nerve pain. Studies have shown that this treatment holds promise by blocking a specific protein linked to pain. In this trial, participants in the Eptinezumab Group will receive eptinezumab infusions, while those in the Placebo Group will receive placebo infusions during the 24-week placebo-controlled treatment period. For people with migraines, eptinezumab significantly reduced the number of migraine days compared to a placebo, suggesting it might also help with other types of pain, such as diabetic neuropathy. Although research on its effects for diabetic neuropathy continues, early results are promising for its ability to relieve pain. ^{1 2 3 5 6}

Who Is on the Research Team?

Narayan Kissoon, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults with painful diabetic neuropathy who've had symptoms for over 6 months, have a pain score of ≥4, and meet specific diagnostic criteria. Excluded are those on high-dose opioids or other recent neuropathic treatments, with chronic wounds, planned major surgery, BMI ≥39 kg/m^2, history of certain mental health conditions or significant cardiovascular disease.

Inclusion Criteria

I have had pain in my feet and lower legs for more than 6 months.

I have nerve pain as defined by specific guidelines.

I have been diagnosed with diabetic nerve damage.

Exclusion Criteria

Unable to understand Danish (Danish site only).

My leg pain is not caused by diabetes but could be due to other reasons like chemotherapy or vitamin deficiency.

I am scheduled for a major surgery during the treatment period.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 infusions of eptinezumab or placebo during the 24-week placebo-controlled treatment period

24 weeks

2 visits (in-person)

Open-label extension

Participants have the option to continue into a 24-week active study treatment period with eptinezumab

24 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Eptinezumab

Trial Overview The study tests the effectiveness of Eptinezumab (a CGRP monoclonal antibody) against a placebo in reducing pain intensity in patients with diabetic polyneuropathy. Participants will be randomly assigned to receive either the medication or placebo to compare outcomes.

How Is the Trial Designed?

Group I: Open-label Eptinezumab Group Experimental Treatment 1 Intervention

At the end of the placebo-controlled treatment period, all participants will have the option to continue into the 24-week long active study treatment period and will receive 2 infusions of eptinezumab.

Group II: Eptinezumab Group Experimental Treatment 1 Intervention

Subjects diagnosed with diabetic polyneuropathy (DPN) will receive 2 infusions of eptinezumab during the 24 week-long placebo-controlled treatment period.

Group III: Placebo Group Placebo Group 1 Intervention

Subjects diagnosed with diabetic polyneuropathy (DPN) will receive 2 infusions of placebo during the 24-week long placebo-controlled treatment period.

Eptinezumab is already approved in United States for the following indications:

Approved in United States as Vyepti for:

• Preventive treatment of migraine in adults

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

A study analyzing 735 reports of peripheral neuropathies (PNs) in cancer patients treated with immune checkpoint inhibitors (ICIs) from 2010 to 2020 found serious adverse reactions, including Guillain-Barré syndrome, which can lead to significant disability or hospitalization.

The analysis indicated that atezolizumab was associated with a higher frequency of PNs compared to other ICIs, highlighting the need for ongoing safety monitoring of these treatments in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do peripheral neuropathies differ among immune checkpoint inhibitors? Reports from the European post-marketing surveillance database in the past 10 years. Ruggiero, R., Balzano, N., Di Napoli, R., et al.[2023]

In a 24-month study involving four pediatric patients with a specific genetic mutation, eculizumab treatment led to significant neurological improvements, particularly in upper limb and trunk function, while allowing for the complete cessation of corticosteroid and IVIG treatments.

Eculizumab was found to be safe, with no relapses or hospital admissions during treatment, and it significantly reduced harmful protein deposition on red blood cells and neutrophils, indicating its potential as a life-saving therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy with eculizumab for patients with CD59 p.Cys89Tyr mutation. Mevorach, D., Reiner, I., Grau, A., et al.[2022]

Rituximab, a chimeric anti-CD20 monoclonal antibody, has shown promise in treating treatment-resistant peripheral neuropathy associated with IgM gammopathy, offering a favorable side-effect profile compared to traditional treatments.

While large controlled studies are still needed, rituximab is administered at 375 mg/m² intravenously over four weekly doses, potentially providing a new therapeutic option for patients suffering from this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in the treatment of peripheral neuropathy associated with monoclonal gammopathy. Zivković, SA.[2015]

In a study of four patients with IgM paraproteinaemic neuropathy, treatment with pulsed intravenous fludarabine led to both subjective and objective clinical improvements, along with a significant reduction in IgM paraprotein levels in three patients.

The treatment was well tolerated, with only mild and reversible side effects such as lymphopenia and mild myelosuppression, suggesting fludarabine could be a promising option for managing this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of IgM paraproteinaemic neuropathy with fludarabine. Wilson, HC., Lunn, MP., Schey, S., et al.[2023]

Pembrolizumab, a monoclonal antibody that targets the PD-1 receptor, effectively enhances T-cell activity to combat cancer, but it can also lead to autoimmune reactions affecting healthy tissues.

In a rare case, a patient developed autoimmune demyelinating polyneuropathy and hydrocephalus after receiving pembrolizumab for cutaneous squamous cell carcinoma, highlighting the potential for serious neuromuscular complications as an immune-related adverse event.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Rare Case of Autoimmune Demyelinating Polyneuropathy and Hydrocephalus Secondary to Pembrolizumab. Arora, A., Shere, A., Patel, K., et al.[2021]

In a review of 2225 lymphoma patients from 4 randomized controlled trials, brentuximab vedotin was found to significantly increase the risk of all-grade adverse events (AEs) and high-grade AEs compared to non-brentuximab vedotin treatments.

Specific AEs associated with brentuximab vedotin included a higher risk of peripheral sensory neuropathy, pyrexia, nausea, vomiting, diarrhea, and alopecia, with particularly high risks for high-grade sensory neuropathy and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of adverse events in lymphoma patients treated with brentuximab vedotin: a systematic review and meta-analysis. Gao, S., Zhang, M., Wu, K., et al.[2021]

In a study of 416 rheumatoid arthritis patients treated with Janus kinase inhibitors (JAKis), 7.9% experienced herpes zoster (HZ) reactivation, with most continuing JAKi treatment during the episode without significant complications.

Among the 29 patients monitored after HZ reactivation, only one (3.4%) had a recurrence, suggesting that continuing JAKi therapy post-HZ reactivation is generally safe and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of JAK inhibitor use in patients with rheumatoid arthritis who developed herpes zoster after receiving JAK inhibitors. Choi, W., Ahn, SM., Kim, YG., et al.[2022]

Monomethyl auristatin E (MMAE) is a commonly used payload in antibody-drug conjugates (ADCs) that has significantly enhanced the effectiveness of cancer treatments, particularly against various malignancies.

However, there is a growing concern about the risk of peripheral neuropathy associated with MMAE-based ADCs, highlighting the need for better diagnostic and management strategies for this adverse effect as their use becomes more widespread.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral neuropathy associated with monomethyl auristatin E-based antibody-drug conjugates. Fu, Z., Gao, C., Wu, T., et al.[2023]

Pembrolizumab, a monoclonal antibody that enhances the immune response against tumors, can lead to serious immune-related adverse events (irAEs) such as myasthenia gravis and peripheral neuropathy, as demonstrated in two reported cases.

Both patients improved after discontinuing pembrolizumab and receiving supportive therapies, highlighting the importance of early recognition and management of these rare side effects to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-Induced Myasthenia Gravis and Peripheral Neuropathy: A Case Series. McCormack, SM., Hamad, A.[2023]

In a study of 10 patients with juvenile dermatomyositis (JDM) treated with Janus kinase inhibitors (JAKis) for at least 6 months, 5 patients achieved clinically inactive disease, indicating that JAKis can be effective for refractory cases.

While JAKis showed promise in improving muscle vasculopathy and reducing steroid use, there was a notable risk of herpes zoster infections in some patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibitors are effective in a subset of patients with juvenile dermatomyositis: a monocentric retrospective study. Le Voyer, T., Gitiaux, C., Authier, FJ., et al.[2021]

In a study of 101 patients with juvenile dermatomyositis (JDM), Janus kinase inhibitors (JAKi) showed promising results, with 65.5% of patients experiencing improved rashes and 39.6% able to eliminate glucocorticoids after a median follow-up of 19 months.

Cytokine analysis revealed that certain cytokines, particularly IL-1RA, were significantly elevated in active JDM patients, and a panel of six cytokines was developed to effectively differentiate between active and stable disease states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of Janus-kinase inhibitor and novel active disease biomarker in juvenile dermatomyositis. Huang, B., Wang, X., Niu, Y., et al.[2023]

In a pilot study involving three children with refractory juvenile dermatomyositis (JDM), tofacitinib, a Janus kinase inhibitor, was well-tolerated and led to significant improvements in muscle strength and overall disease activity over a 6-month period.

Tofacitinib also allowed for successful tapering of steroids and improved quality of life, suggesting it may be a promising treatment option for children with difficult-to-treat JDM, although further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful management with Janus kinase inhibitor tofacitinib in refractory juvenile dermatomyositis: a pilot study and literature review. Yu, Z., Wang, L., Quan, M., et al.[2021]

In a Phase 2 study involving 129 adults with Type 2 diabetes at high risk for diabetic kidney disease, baricitinib (4 mg daily) significantly reduced morning urine albumin-creatinine ratio (UACR) by 41% after 24 weeks compared to placebo, indicating its efficacy in lowering albuminuria.

Baricitinib also decreased several inflammatory biomarkers over the study period, although it was associated with a higher rate of anemia (32%) compared to placebo (3.7%), highlighting a potential safety concern that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK1/JAK2 inhibition by baricitinib in diabetic kidney disease: results from a Phase 2 randomized controlled clinical trial. Tuttle, KR., Brosius, FC., Adler, SG., et al.[2021]

Rituximab alone has a low response rate (around 30%) for treating IgM-related neuropathy, but combining it with fludarabine has shown promise in stabilizing or improving symptoms in patients, including those resistant to rituximab.

The combination therapy was well-tolerated and may help overcome resistance to rituximab, suggesting it could be a valuable treatment option for patients with insufficient response to rituximab monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine may overcome resistance to rituximab in IgM-related neuropathy. Koya, J., Iwata, A., Nakamura, F., et al.[2015]

A case of severe generalized myasthenia gravis presented with symptoms resembling a partial cranial nerve 3 palsy, which did not improve with standard treatments like pyridostigmine and intravenous immunoglobulin.

The patient's condition significantly improved after treatment with eculizumab, indicating that this medication may be a valuable option for patients with refractory ocular myasthenia gravis and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Refractory generalized myasthenia gravis with myasthenic incomplete ophthalmoplegia successfully treated with eculizumab. Weidmayer, SL., Gallagher, G.[2023]

Citations

1. clinicaltrials.eu clinicaltrials.eu/trial/study-on-eptinezumab-for-painful-diabetic-neuropathy-in-adults/

Study on Eptinezumab for Painful Diabetic Neuropathy in ... The purpose of the study is to evaluate how effective eptinezumab is in decreasing pain levels over a period of 24 weeks. Participants in the ...

2. withpower.com withpower.com/trial/phase-2-diabetic-neuropathies-6-2023-ee13e

Eptinezumab for Diabetic Neuropathy · Info for Participants The main purpose of this study is to compare the change in pain intensity during treatment with a CGRP monoclonal antibody (eptinezumab) compared with placebo ...

3. vyeptihcp.com vyeptihcp.com/efficacy-and-patient-outcomes

Efficacy & Patient Outcomes | VYEPTI® (eptinezumab-jjmr) Patients experienced, on average, 23.1 (VYEPTI 100 mg) and 24.6 (VYEPTI 300 mg) fewer migraine days over weeks 1-12 vs 16.8 with placebo* (baseline ~16.1 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11571639/

Diabetic Peripheral Neuropathy: Emerging Treatments of ... Overall, the evidence for efficacy and safety is consistently growing in favor of spinal cord stimulation. The main obstacles for spinal cord stimulation use in ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05937152/a-study-of-cgrp-monoclonal-antibody-to-treat-diabetic-neuropathy

A Study of CGRP Monoclonal Antibody to Treat Diabetic ... The main purpose of this study is to compare the change in pain intensity during treatment with a CGRP monoclonal antibody (eptinezumab) compared with placebo ...

6. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1355877/full

Eptinezumab for the preventive treatment of episodic and ... Collectively, results from pooled data from clinical trials has demonstrated that eptinezumab, in general, is well tolerated, and has a favorable long-term ...