Eptinezumab for Diabetic Neuropathy
Recruiting in Palo Alto (17 mi)
+2 other locations
Overseen ByNarayan Kissoon, MD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Mayo Clinic
Prior Safety Data
Approved in 1 jurisdiction
Trial Summary
What is the purpose of this trial?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 treatment in patients with painful diabetic polyneuropathy (DPN).
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 the drug Eptinezumab a promising treatment for diabetic neuropathy?
The provided research articles do not mention Eptinezumab or its effects on diabetic neuropathy, so we cannot determine if it is a promising treatment based on this information.
123413What safety data is available for Eptinezumab (Vyepti) in treating diabetic neuropathy?
The provided research does not contain specific safety data for Eptinezumab (Vyepti) in the treatment of diabetic neuropathy. The studies focus on other drugs and their associated adverse events, particularly peripheral neuropathy, but do not mention Eptinezumab or its safety profile.
67121415What data supports the idea that Eptinezumab for Diabetic Neuropathy is an effective treatment?
The available research does not provide any data on Eptinezumab for Diabetic Neuropathy. Instead, it focuses on Janus kinase inhibitors for other conditions like rheumatoid arthritis, juvenile dermatomyositis, and diabetic kidney disease. Therefore, there is no information here to support the effectiveness of Eptinezumab for Diabetic Neuropathy.
5891011Eligibility Criteria
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 been diagnosed with diabetic nerve damage.
Exclusion Criteria
I have a history of serious heart or blood vessel problems.
I am scheduled for a major surgery during the treatment period.
I am on a stable, low dose of Tramadol (200 mg/day or less) or not taking opioids.
I have poor blood flow in my legs, indicated by low toe pressure or lack of foot pulses.
I have used CGRP inhibitors for treatment.
I have long-lasting, non-healing wounds.
Participant Groups
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.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: Open-label Eptinezumab GroupExperimental Treatment1 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 GroupExperimental Treatment1 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 GroupPlacebo Group1 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Mayo Clinic MinnesotaRochester, MN
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Who is running the clinical trial?
Mayo ClinicLead Sponsor
References
Successful treatment of IgM paraproteinaemic neuropathy with fludarabine. [2023]To evaluate the response of four patients with IgM paraproteinaemic neuropathy to a novel therapy-pulsed intravenous fludarabine.
Rituximab in the treatment of peripheral neuropathy associated with monoclonal gammopathy. [2015]Peripheral neuropathy associated with immunoglobulin (Ig)M gammopathy and anti-myelin-associated glycoprotein antibodies is frequently treatment-resistant and different treatment regimens carry substantial toxicity and side effects. More recently, the chimeric anti-CD20 monoclonal antibody rituximab has shown benefits in the treatment of peripheral neuropathy associated with IgM gammopathy with a favorable side-effect profile. There are no published reports of its use in the treatment of neuropathy associated with IgG and IgA gammopathies. Rituximab is usually given at 375 mg/m(2) intravenously with four weekly doses that may be repeated after 6-12 months. Large controlled studies are still pending but rituximab is an exciting and promising treatment offering another option in the treatment of peripheral neuropathy associated with IgM monoclonal gammopathy.
Fludarabine may overcome resistance to rituximab in IgM-related neuropathy. [2015]Rituximab, a monoclonal antibody directed against CD20, became widely used for the treatment of immunoglobulin M (IgM)-related neuropathy. However, response rate by rituximab monotherapy is no more than 30%. Previous studies revealed that fludarabine acts synergistically with rituximab in vitro and that fludarabine also ameliorates IgM-related neuropathy in a subset of patients. Here we present two cases of IgM-related neuropathy in the background of Waldenström macroglobulinaemia, including one with rituximab resistance. They showed marginal to high titres of both anti-myelin associated glycoprotein and anti-sulphate-3-glucuronyl paragloboside antibodies, and their symptoms were featured by prominent motor deterioration. The combination therapy with rituximab and fludarabine stabilised or improved neuropathic symptoms with tolerable adverse events. Fludarabine may have a potential to overcome rituximab resistance. In conclusion, combination therapy with rituximab and fludarabine should be considered for IgM-related neuropathy, especially when efficacy of rituximab monotherapy is insufficient.
Therapy with eculizumab for patients with CD59 p.Cys89Tyr mutation. [2022]The objective of this work was to report on the outcome of eculizumab treatment in pediatric patients with recurrent acute predominantly motor, demyelinating neuropathy with conduction block, and chronic hemolysis attributed to p.Cys89Tyr mutation in the CD59 gene.
JAK1/JAK2 inhibition by baricitinib in diabetic kidney disease: results from a Phase 2 randomized controlled clinical trial. [2021]Inflammation signaled by Janus kinases (JAKs) promotes progression of diabetic kidney disease (DKD). Baricitinib is an oral, reversible, selective inhibitor of JAK1 and JAK2. This study tested the efficacy of baricitinib versus placebo on albuminuria in adults with Type 2 diabetes at high risk for progressive DKD.
Risk of adverse events in lymphoma patients treated with brentuximab vedotin: a systematic review and meta-analysis. [2021]Objectives: To assess the risk of adverse events (AEs) associated with brentuximab vedotin in lymphoma patients.Methods: Articles were retrieved from PubMed, Cochrane, and Clinicaltrials Databases to identify randomized controlled trials (RCTs) comparing brentuximab vedotin with non-brentuximab vedotin in lymphoma patients.Results: A total of 2225 patients from 4 RCTs were included. Compared with the non-brentuximab vedotin group, the brentuximab vedotin group significantly increased the risk of all-grade AEs (RR 1.05, 95% CI: 1.00-1.10), and high-grade AEs (risk ratio [RR] 1.27, 95% confidence intervals [CI]: 1.01-1.58). The brentuximab vedotin group significantly increased the risk of all-grade peripheral sensory neuropathy (RR 2.29, 95% CI: 1.23-4.26), pyrexia (RR 1.23, 95% CI: 1.05-1.44), nausea (RR 1.51, 95% CI: 1.05-2.18), vomiting (RR 1.54, 95% CI: 1.08-2.19), diarrhea (RR 1.69, 95% CI: 1.44-1.98), and alopecia (RR 1.18, 95% CI: 1.00-1.39), respectively. The brentuximab vedotin group significantly increased the risk of high-grade sensory neuropathy (RR 4.79, 95% CI: 1.46-15.75), neutropenia (RR 1.48, 95% CI: 1.01-2.18), nausea (RR 2.65, 95% CI: 1.37-5.12), vomiting (RR 2.2, 95% CI: 1.17-4.12), and diarrhea (RR 1.85, 95% CI: 1.21-2.85).Conclusion: Brentuximab vedotin increased the risk of certain AEs in lymphoma patients.
A Rare Case of Autoimmune Demyelinating Polyneuropathy and Hydrocephalus Secondary to Pembrolizumab. [2021]Pembrolizumab is a humanized monoclonal antibody that targets the programmed cell death 1 protein (PD-1) receptor and blocks the inhibitory checkpoint interaction between PD-1 and its ligands. This interaction leads to the upregulation of effector T-cells and downregulating regulatory T-cell production. Although this mechanism is essential for the management of cancer, it may lead to decreased self-tolerance with an autoimmune reaction toward healthy functioning tissue. One of the less commonly reported and less understood immune-related adverse events includes neuromuscular complications. We present a rare case of autoimmune demyelinating polyneuropathy and hydrocephalus secondary to pembrolizumab use for cutaneous squamous cell carcinoma of the cheek.
Successful management with Janus kinase inhibitor tofacitinib in refractory juvenile dermatomyositis: a pilot study and literature review. [2021]JDM is a rare autoimmune inflammatory muscle disease with a pronounced IFN signature. Treatment for children with JDM has improved over the years with the use of steroids and immunosuppressive agents. However, there remains a subset of children who have refractory disease. Janus kinase and type I IFN signalling production are suspected to contribute to the pathogenesis of JDM. Our pilot study investigated the use of tofacitinib, a Janus kinase inhibitor, in refractory JDM cases to provide new therapeutic options for better treatment.
JAK inhibitors are effective in a subset of patients with juvenile dermatomyositis: a monocentric retrospective study. [2021]To evaluate the efficacy and safety of Janus kinase inhibitors (JAKis) in JDM.
Safety of JAK inhibitor use in patients with rheumatoid arthritis who developed herpes zoster after receiving JAK inhibitors. [2022]To determine the safety of Janus kinase inhibitor (JAKi) use following herpes zoster (HZ) reactivation in patients with rheumatoid arthritis (RA).
Long-term follow-up of Janus-kinase inhibitor and novel active disease biomarker in juvenile dermatomyositis. [2023]To evaluate the use of Janus kinase inhibitor (JAKi) in treating JDM and develop cytokine biomarkers of active disease.
Do peripheral neuropathies differ among immune checkpoint inhibitors? Reports from the European post-marketing surveillance database in the past 10 years. [2023]Although the immunotherapy advent has revolutionized cancer treatment, it, unfortunately, does not spare cancer patients from possible immune-related adverse events (irAEs), which can also involve the peripheral nervous system. Immune checkpoint inhibitors (ICIs), blocking cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death ligand 1 (PD-L1), can induce an immune imbalance and cause different peripheral neuropathies (PNs). Considering the wide range of PNs and their high impact on the safety and quality of life for cancer patients and the availability of large post-marketing surveillance databases, we chose to analyze the characteristics of ICI-related PNs reported as suspected drug reactions from 2010 to 2020 in the European real-world context. We analyzed data collected in the European pharmacovigilance database, Eudravigilance, and conducted a systematic and disproportionality analysis. In our study, we found 735 reports describing 766 PNs occurred in patients treated with ICIs. These PNs included Guillain-Barré syndrome, Miller-Fisher syndrome, neuritis, and chronic inflammatory demyelinating polyradiculoneuropathy. These ADRs were often serious, resulting in patient disability or hospitalization. Moreover, our disproportionality analysis revealed an increased reporting frequency of PNs with tezolizumab compared to other ICIs. Guillain-Barré syndrome is a notable potential PN related to ICIs, as it is associated with a significant impact on patient safety and has had unfavorable outcomes, including a fatal one. Continued monitoring of the safety profile of ICIs in real-life settings is necessary, especially considering the increased frequency of PNs associated with atezolizumab compared with other ICIs.
Refractory generalized myasthenia gravis with myasthenic incomplete ophthalmoplegia successfully treated with eculizumab. [2023]This is a case of myasthenic incomplete ophthalmoplegia mimicking a partial cranial nerve 3 palsy both subjectively and objectively improving after treatment with eculizumab.
Peripheral neuropathy associated with monomethyl auristatin E-based antibody-drug conjugates. [2023]Since the successful approval of gemtuzumab ozogamicin, antibody-drug conjugates (ADCs) have emerged as a pivotal category of targeted therapies for cancer. Among these ADCs, the use of monomethyl auristatin E (MMAE) as a payload is prevalent in the development of ADC drugs, which has significantly improved overall therapeutic efficacy against various malignancies. However, increasing clinical observations have raised concerns regarding the potential nervous system toxicity associated with MMAE-based ADCs. Specifically, a higher incidence of peripheral neuropathy has been reported in ADCs incorporating MMAE as payloads. Considering the increasing global use of MMAE-based ADCs, it is imperative to provide an inclusive overview of diagnostic and management strategies for this adverse event. In this review, we examine current information and what future research directions are required to better understand and manage this type of clinical challenge.
Pembrolizumab-Induced Myasthenia Gravis and Peripheral Neuropathy: A Case Series. [2023]Pembrolizumab is a monoclonal antibody that targets the programmed cell death protein 1 (PD-1) receptor on T-cells, thereby enhancing the antitumor immune response. Pembrolizumab has been shown to improve survival in various cancers, but it can also cause immune-related adverse events (irAEs), which can affect any organ system. We report two cases of rare but serious irAEs caused by pembrolizumab: myasthenia gravis (MG) and peripheral neuropathy. Both patients presented with neuromuscular symptoms after receiving pembrolizumab for their advanced cancers. They were diagnosed with MG and peripheral neuropathy based on their clinical features, laboratory tests, and unremarkable imaging. Treatment involved discontinuing pembrolizumab and initiating immunosuppressive and supportive therapies. Both patients experienced improvement in their symptoms and quality of life once pembrolizumab was permanently discontinued and supportive therapies were in place. These cases highlight the importance of recognizing and managing rare irAEs of pembrolizumab, such as MG and peripheral neuropathy. Early diagnosis and treatment can improve outcomes and reduce morbidity. Furthermore, these cases emphasize the need for continued post-marketing surveillance to accurately assess the risk of less frequent adverse drug reactions seen in patients on pembrolizumab. Knowledge of these adverse reactions is important when discussing the pros and cons of this novel therapy with patients.