EPPIC-Net Pain Research - Application for Clinical Trial and Related Activities (OT2)

EPPIC-Net Pain Research - 临床试验及相关活动申请 (OT2)

• 批准号: 10267804
• 负责人: MAURIZIO FAVA
• 金额: $ 1301.6万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-03-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10267804
• 关键词: Absence of pain sensation; Ache; Acute Pain; Address; Adult; Affect; Aftercare; Analgesics; Asia; Award; Barbiturates; Behavioral; Biological; Blood specimen; Characteristics; Clinical; Clinical Research; Clinical Trials; Clinical Trials Network; Collection; Common Data Element; Cream; Data Collection; Data Set; Devices; Diabetes Mellitus; Dose; Double-Blind Method; Elderly; Elements; Enrollment; Europe; Exhibits; FDA approved; Functional disorder; Funding; Gastric ulcer; Genotype; Helping to End Addiction Long-term; Hospitals; Hour; Hypersensitivity; Individual; Inflammatory; Infrastructure; Injections; Intervention; Joints; Knee Osteoarthritis; Laboratory Finding; Lead; Length of Stay; Measurement; Measures; Modernization; Nerve; Nerve Fibers; Neurosecretory Systems; Non-Insulin-Dependent Diabetes Mellitus; Operative Surgical Procedures; Opioid; Oral; Outcome; Pain; Pain Research; Pain management; Participant; Patients; Peripheral Nervous System Diseases; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Pirenzepine; Placebos; Procedures; Prognostic Marker; Protocols documentation; Randomized; Recording of previous events; Research; Risk; Safety; Sampling; Secure; Sensory; Siberia; Site; Skin; Structure; Tea; Testing; Therapeutic; Time; Topical application; Touch sensation; Transcranial Doppler Ultrasonography; Ultrasonography; United States National Institutes of Health; Vasospasm; Woman; addiction; bench to bedside; beta-Chemokines; chronic pain; clinical application; clinical investigation; clinical predictors; clinical research site; clinically relevant; density; design; diabetic; early phase clinical trial; effective therapy; experience; foot; inflammatory marker; interest; men; microbiome analysis; neuroinflammation; neurotransmission; novel; novel therapeutics; opioid exposure; opioid overdose; opioid use; osteoarthritis pain; pain model; pain relief; painful neuropathy; phenotypic biomarker; placebo controlled study; preclinical study; predicting response; predictive marker; psychological distress; receptor; response biomarker; sex; small molecule; sociodemographic predictors; sociodemographics; stem; therapeutic development; therapeutic evaluation; translational medicine; trial design

This OT Award funds clinical trials within The Early Phase Pain Investigation Clinical Network (EPPIC-Net). EPPIC-NET is part of the NIH Helping to End Addiction Long-term (HEAL) Initiative. More than 100 people die each day of opioid-related overdoses. Many of these can be traced to addiction related to the treatment of acute and chronic pain. There is an urgent need to develop non-addictive pain treatments to limit opioid exposures that can lead to addiction, as well as to treat pain conditions that are currently without effective treatments. The EPPIC- Net OT provides a robust infrastructure for the rapid design and execution of high-quality early phase clinical trials to test promising novel therapeutics and devices for the treatment of pain and for carrying out in-depth phenotyping and biomarker studies in patients with specific pain conditions. Such studies bring intense focus to patients with well-defined pain conditions and high unmet therapeutic needs. Studies funded under this award are described below. EPPIC-Net Clinical Trial EN20-01 Project Title: A 24-week Week Study to Evaluate the Safety and Efficacy of CNTX-6970 in Subjects with Moderate to Severe Knee Osteoarthritis Pain. This trial will test the novel oral drug CNTX-6970 in patients with moderate to severe knee osteoarthritis pain. 150 participants will be enrolled at 20 EPPIC-Net sites across the U.S. Preclinical studies of CNTX-6970, a C-C chemokine type 2 (CCR2) receptor antagonist, demonstrated potent analgesia in multiple pain models. Phase 1 clinical studies showed robust and dose-proportional target engagement and no emergent safety issues. The rationale for exploring CNTX-6970 for the management of pain in knee osteoarthritis stems from the emerging understanding of the pathophysiology of the affected joint as well as CNTX-6970 effects on neural signaling. Participants will be randomized to receive CNTX-6970, placebo, or an approved pain medication and will be followed for 24 weeks. EPPIC-Net Master Protocol to Assess Treatments for Painful Diabetic Peripheral Neuropathy People with diabetes are at risk for painful diabetic peripheral neuropathy. Diabetic neuropathic pain may be experienced as burning, aching, hypersensitivity to touch, or simply as pain. The currently FDA-approved medications for painful diabetic peripheral neuropathy (PDPN) provide inadequate pain relief for many. The EPPIC-Net Master Protocol for Diabetic Peripheral Neuropathy (Master Platform Protocol (MPP)) provides a platform for EPPIC-Net Phase II clinical trials testing therapeutic assets for the treatment of PDPN. The MPP provides the common over-arching structure with a modular design of required and optional elements to be included for study of each asset. All clinical trials under the MPP include HEAL Common Data Elements and required PDPN assessments as well as asset-specific procedures and measurements described in an Intervention Specific Appendix (ISA) to the MPP. The following EPPIC-Net Clinical Trials will be conducted under the EPPIC-NET Master Protocol to assess treatments for painful diabetic peripheral neuropathy: EPPIC-Net Clinical Trial EN21-01 Project Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of 80mg daily of NRD135S.E1 Versus Placebo in Adult and Elderly Participants with Painful Diabetic Peripheral Neuropathy (SERENDIPITY-1) This award is for a clinical trial under the EPPIC-Net Master Protocol for Painful Diabetic Peripheral Neuropathy. The identification of NRD135S.E1 as a potential pain treatment is a true “bedside-to-bench" story in modern-day translational medicine. NRD135S.E1 is a small molecule, a lab-optimized version of a natural substance traditionally used in a village in Siberia to brew tea to treat pain. In clinical studies, NRD135S.E1 was well tolerated by participants and showed clinically relevant pain relief. Study in EPPIC-Net will further development of this therapeutic asset as a possible treatment for painful diabetic peripheral neuropathy (PDPN). 260 adult participants with PDPN will be randomized to NRD135S.E1 or placebo in the 12-week, parallel design trial. EPPIC-Net Clinical Trial EN21-02 Project Title: A Randomized, Double-blind, Placebo-controlled, Parallel, 20-week, Phase 2b Study of Topical Pirenzepine (WST-057) or Placebo in Type 2 Diabetes Mellitus Patients with Painful Diabetic Peripheral Neuropathy This award is for a clinical trial under EPPIC-Net Master Protocol for Painful Diabetic Peripheral Neuropathy to test a potential new topical treatment for painful diabetic peripheral neuropathy. The therapeutic asset, WST-057 (topical pirenzepine 4%), is a molecule that was developed in the 1980s and marketed throughout Europe and Asia in an oral form to treat gastric ulcers. Preliminary studies showed an increase in nerve fiber density in the skin, suggesting it can enhance nerve regrowth and may help alleviate pain in painful diabetic peripheral neuropathy as well. This EPPIC-Net study will enroll 260 participants at 12 clinical sites. Participants will be randomized to apply WST-057 or a matching placebo cream to the feet and calves for 20-weeks.

该OT奖在早期疼痛调查临床网络（EPPIC-NET）中为临床试验提供了资金。 Eppic-NET是NIH的一部分，有助于长期结束成瘾（治愈）倡议。每天有100多人死于阿片类药物有关的过量服用。其中许多可以追溯到与急性和慢性疼痛治疗有关的成瘾。迫切需要开发非疼痛治疗，以限制可能导致成瘾的阿片类药物暴露，以及治疗目前没有有效治疗的疼痛状况。 Eppic-Net OT为快速设计和高质量的早期临床试验的快速设计和执行提供了强大的基础设施，以测试有希望的新型治疗和用于治疗疼痛的设备，并在具有特定疼痛条件的患者中进行深入的表型和生物标志物研究。此类研究将明确的疼痛状况和高未满足治疗需求的患者重视。根据该奖项资助的研究如下所述。 Eppic-NET临床试验EN20-01 项目标题：一项为期24周的研究，旨在评估CNTX-6970在中度至重度膝关节骨关节炎疼痛的受试者中的安全性和功效。 该试验将对中度至重度骨关节炎疼痛的患者进行新的口服药物CNTX-6970测试。在美国CNTX-6970（C-C趋化因子2型（CCR2）受体拮抗剂的CNTX-6970）中，将在20个EPPIC-NET位点招募150名参与者，在多种疼痛模型中表现出潜在的镇痛作用。第1阶段的临床研究表明，稳健和剂量的目标参与度，没有新兴的安全问题。探索CNTX-6970的基本原理，用于管理膝盖骨关节炎疼痛的步骤，从对受影响关节的病理生理以及CNTX-6970对神经信号的影响的新兴理解以及对神经信号的影响。参与者将被随机接受CNTX-6970，安慰剂或批准的止痛药，并将遵循24周。 EPPIC-NET总体方案评估疼痛糖尿病周围神经病的治疗方法 糖尿病患者有疼痛糖尿病周围神经病的风险。糖尿病神经性疼痛可能会经历，因为燃烧，酸痛，触摸过敏或仅仅是疼痛。目前已通过FDA批准的用于疼痛糖尿病周围神经病（PDPN）的药物可减轻许多人的疼痛缓解。 EPPIC-NET糖尿病外周神经病的总体方案（主平台协议（MPP））为EPPIC-NET II期临床试验测试治疗PDPN的治疗资产提供了平台。 MPP提供了常见的架构结构，其模块化设计是所需的和可选元素，以研究每个资产。 MPP下的所有临床试验均包括治愈共同数据元素以及所需的PDPN评估以及在MPP的干预特定附录（ISA）中所述的资产特定程序和测量。 以下Eppic-NET临床试验将根据Eppic-NET总体方案进行，以评估疼痛糖尿病周围神经病的治疗方法： Eppic-NET临床试验EN21-01 项目标题：一项多中心，随机，双盲，安慰剂对照研究，以评估NRD135S.E1每天80mg每日的安全性和功效，而成人和成年人的糖尿病性糖尿病周围神经病（Serendipity-1） 该奖项是针对Eppic-NET疼痛糖尿病周围神经病的Eppic-NET总体方案进行的临床试验。 NRD135S.E1作为一种潜在的疼痛治疗是现代翻译医学中真正的“床头到台式”故事。 NRD135S.E1是一个小分子，是西伯利亚村庄传统上使用的天然物质的实验室优化版本，以酿造茶来治疗疼痛。在临床研究中，NRD135S.E1受到参与者的耐受性良好，并显示出临床相关的疼痛缓解。 EPPIC-NET的研究将进一步开发这种治疗性，作为疼痛糖尿病周围神经病（PDPN）的可能治疗方法。 260名PDPN的成年参与者将在12周的平行设计试验中随机分为NRD135S.E1或安慰剂。 Eppic-NET临床试验EN21-02 项目标题：随机，双盲，安慰剂对照，平行，20周，局部2B研究局部吡renzepine（WST-057）或2型糖尿病中的安慰剂或安慰剂 该奖项是针对Eppic-NET总体方案进行的临床试验，用于疼痛的糖尿病周围神经病，以测试潜在的疼痛糖尿病外周神经病的新局部治疗方法。治疗性资产，WST-057（局部pirenzepine 4％），是一种分子，在1980年代开发，在整个欧洲和亚洲以口服形式销售以治疗胃溃疡。初步研究表明，皮肤的神经纤维密度增加，这表明它可以增强神经退化，并有助于减轻疼痛糖尿病周围神经病的疼痛。这项EPPIC网络研究将在12个临床部位招募260名参与者。参与者将被随机分配给WST-057或匹配的安慰剂霜，并为20周的犊牛涂抹。