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 奖项资助早期疼痛调查临床网络 (EPPIC-Net) 内的临床试验。 EPPIC-NET 是 NIH 帮助消除成瘾长期 (HEAL) 计划的一部分。每天有超过 100 人死于与阿片类药物相关的过量服用。其中许多可以追溯到与急性和慢性疼痛治疗相关的成瘾。迫切需要开发非成瘾性疼痛治疗方法，以限制可能导致成瘾的阿片类药物暴露，并治疗目前尚无有效治疗方法的疼痛状况。 EPPIC-Net OT 为快速设计和执行高质量的早期临床试验提供了强大的基础设施，以测试用于治疗疼痛的有前景的新型疗法和设备，以及对患有特定疼痛状况的患者进行深入的表型分析和生物标志物研究。此类研究将重点关注具有明确疼痛状况和高度未满足治疗需求的患者。该奖项资助的研究如下所述。 EPPIC-Net 临床试验 EN20-01 项目名称：一项为期 24 周的研究，旨在评估 CNTX-6970 对中度至重度膝骨关节炎疼痛受试者的安全性和有效性。 该试验将测试新型口服药物 CNTX-6970 在中度至重度膝骨关节炎疼痛患者中的作用。将在美国 20 个 EPPIC-Net 站点招募 150 名参与者。CNTX-6970 是一种 C-C 趋化因子 2 型 (CCR2) 受体拮抗剂，其临床前研究显示在多种疼痛模型中具有有效的镇痛作用。一期临床研究显示出稳健且与剂量成比例的靶点参与，并且没有紧急的安全问题。探索 CNTX-6970 用于治疗膝骨关节炎疼痛的基本原理源于对受影响关节的病理生理学以及 CNTX-6970 对神经信号传导影响的新认识。参与者将被随机分配接受 CNTX-6970、安慰剂或已批准的止痛药，并随访 24 周。 评估疼痛性糖尿病周围神经病变治疗方法的 EPPIC-Net 主协议 糖尿病患者有患糖尿病性周围神经病变的风险。糖尿病神经性疼痛可能表现为烧灼感、酸痛、触觉过敏或单纯疼痛。目前 FDA 批准的治疗疼痛性糖尿病周围神经病变 (PDPN) 的药物对许多人来说并不能充分缓解疼痛。 EPPIC-Net 糖尿病周围神经病变主协议（主平台协议 (MPP)）为 EPPIC-Net II 期临床试验提供了一个平台，测试治疗 PDPN 的治疗资产。 MPP 提供了通用的总体结构，并对每个资产的研究中包含的必需和可选元素进行了模块化设计。 MPP 下的所有临床试验都包括 HEAL 通用数据元素和所需的 PDPN 评估，以及 MPP 干预特定附录 (ISA) 中描述的资产特定程序和测量。 以下 EPPIC-Net 临床试验将根据 EPPIC-NET 主协议进行，以评估疼痛性糖尿病周围神经病变的治疗方法： EPPIC-Net 临床试验 EN21-01 项目名称：一项多中心、随机、双盲、安慰剂对照研究，旨在评估每日 80 毫克 NRD135S.E1 与安慰剂在患有疼痛性糖尿病周围神经病变的成人和老年参与者中的安全性和有效性 (SERENDIPITY-1) 该奖项是针对 EPPIC-Net 主方案下针对疼痛性糖尿病周围神经病变的临床试验。 NRD135S.E1 被认定为一种潜在的疼痛治疗方法，是现代转化医学中真正的“从床边到工作台”的故事。 NRD135S.E1 是一种小分子，是西伯利亚村庄传统上用来泡茶治疗疼痛的天然物质的实验室优化版本。在临床研究中，NRD135S.E1 被参与者良好耐受，并显示出临床相关的疼痛缓解效果。 EPPIC-Net 中的研究将进一步开发这种治疗资产，作为疼痛性糖尿病周围神经病 (PDPN) 的可能治疗方法。在为期 12 周的平行设计试验中，260 名患有 PDPN 的成年参与者将被随机分配至 NRD135S.E1 或安慰剂组。 EPPIC-Net 临床试验 EN21-02 项目名称：一项随机、双盲、安慰剂对照、平行、20 周、2b 期研究，针对患有疼痛性糖尿病周围神经病变的 2 型糖尿病患者局部使用哌仑西平 (WST-057) 或安慰剂 该奖项是针对 EPPIC-Net 疼痛性糖尿病周围神经病变主方案下的一项临床试验，以测试一种潜在的新型局部治疗方法，用于治疗疼痛性糖尿病周围神经病变。治疗资产 WST-057（局部哌仑西平 4%）是一种于 20 世纪 80 年代开发的分子，以口服形式在欧洲和亚洲销售，用于治疗胃溃疡。初步研究显示皮肤中的神经纤维密度增加，表明它可以增强神经再生，并可能有助于减轻糖尿病周围神经病变的疼痛。这项 EPPIC-Net 研究将在 12 个临床中心招募 260 名参与者。参与者将被随机分配在足部和小腿上涂抹 WST-057 或匹配的安慰剂霜，为期 20 周。