Expanded Clinical Trial of Granulocyte Colony-Stimulating Factor (G-CSF) to Treat Hot Flush and Other Vasomotor Symptoms in Women with Naturally-Occurring and Surgically-Induced Menopause

粒细胞集落刺激因子 (G-CSF) 治疗自然发生和手术引起的更年期女性潮热和其他血管舒缩症状的扩大临床试验

• 批准号: 9907820
• 负责人: James Woodruff Emlen
• 金额: $ 29.98万
• 依托单位: MENOGENIX, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9907820
• 关键词: Ablation; Activities of Daily Living; Acupuncture Therapy; Adoption; Adverse event; African American; Agreement; Alternative Therapies; Analgesics; Antidepressive Agents; Antipsychotic Agents; Australia; Biological; Canada; Cancer Patient; Chest; China; Chronic; Climacteric Arthritis; Clinical; Clinical Research; Clinical Trials; Contracts; Dangerousness; Data; Dementia; Development Plans; Distress; Dose; Double-Blind Method; Enrollment; Europe; FDA approved; Face; Feeling; Feeling suicidal; Flushing; Frequencies; Funding; Goals; Grant; Granulocyte Colony-Stimulating Factor; Health; Healthcare; Heart Diseases; Hormones; Hot flushes; Human; Incidence; Individual; Injections; Institutional Review Boards; Intellectual Property; Israel; Japan; Label; Lead; Legal patent; Licensing; Life; Malignant Neoplasms; Malignant neoplasm of prostate; Manufacturer Name; Menopausal Symptom; Menopause; Methods; Modality; Neck; Neutropenia; Nutraceutical; Operative Surgical Procedures; Opioid; Paroxetine; Peripheral; Pharmacologic Substance; Pharmacology and Toxicology; Phase; Phase I Clinical Trials; Phase Ib Clinical Trial; Physicians; Physiological; Placebos; Proteins; Quality of life; Randomized; Reporting; Risk; Safety; Schedule; Serious Adverse Event; Severities; Small Business Innovation Research Grant; Stroke; Sweating; Symptoms; Testing; Vasodilation; Vasomotor; Woman; addiction; aged; base; chemotherapy; clinical development; commercialization; daily functioning; hormone therapy; industry partner; malignant breast neoplasm; meetings; novel; placebo controlled study; placebo controlled trial; product development; prospective; side effect; symptom treatment

One of the most common and distressing symptoms of menopause are hot flashes. Hot flashes and related symptoms represent a significant unmet, worldwide, healthcare need, not only in women after surgical or natural menopause, but also in breast and prostate cancer patients undergoing hormone suppression or ablation. Hot flashes occur in 65 – 90% of women undergoing natural menopause and approximately 70 million individuals worldwide seek therapy each year (~33% of all women aged 50- 65). A hot flash is a sudden feeling of warmth that is generally most intense over the face, neck and chest as well as peripheral vasodilation leading to flush. The duration is variable but averages about 4 minutes. It is often accompanied by sweating. Although not life-threatening, hot flashes can have a detrimental effect on a woman's functional ability and quality of life. The physiological mechanisms leading to a hot flash episode are not known. Similarly, it is not known how decreasing hormone levels that occur during the menopause transition lead to hot flashes and related symptoms. The only FDA-approved therapies for hot flashes are hormone therapy (HT) and a low dose form of paroxetine, an anti-depressant. HT is associated with severe health risks including heart disease, cancer, stroke and dementia. Paroxetine use is associated with suicidal thoughts and addiction. While there are no other FDA-approved alternatives, physicians often prescribe other anti-depressants, anti-psychotic agents and pain medications, all of which have significant side effects. Seeking less dangerous alternatives, many women turn to alternative therapies including nutraceuticals and acupuncture but none of these have proven to be effective in placebo-controlled trials. An effective, non-hormonal, non-anti-depressant, treatment for hot flashes and related vasomotor symptoms would be a welcome, novel and useful treatment modality. MenoGeniX is repurposing a naturally occurring human protein called G-CSF to treat hot flashes based on placebo-controlled phase 1 clinical trial data which showed that a single administration of G-CSF can lead to a rapid and significant reduction in hot flash frequency and severity in women with natural and surgically-induced menopause. G-CSF was well tolerated: no serious adverse events were reported and adverse events were generally mild, of short duration, and should not impact clinical adoption. Women with surgically-induced menopause as well as African-American women responded especially well. In this phase 1 SBIR application, we are requesting funding to evaluate the safety and efficacy of G-CSF administered monthly (three single injections at 28-day intervals) to treat menopausal hot flashes. With a well-established safety record, G-CSF may represent a valuable alternative for women who are unwilling or unable to take HT, paroxetine, off-label anti-depressants, anti-psychotic agents, and pain medications, including opioids.

更年期最常见和最痛苦的症状之一是潮热。潮热和 相关症状代表了一个重大的未满足的，世界范围内的医疗保健需求，不仅在妇女中， 手术或自然绝经，而且在乳腺癌和前列腺癌患者接受激素 抑制或消融。潮热发生在65 - 90%的经历自然绝经的妇女中， 全世界每年约有7000万人寻求治疗（约33%的50岁以下女性）。 65）。潮热是一种突然的温暖感觉，通常在面部、颈部和颈部最强烈， 胸部以及外周血管扩张导致潮红。持续时间是可变的，但平均约4 分钟它经常伴随着出汗。虽然不危及生命，但潮热可能有一个 对妇女的功能和生活质量产生不利影响。的生理机制 导致潮热发作的原因尚不清楚。同样，我们也不知道减少激素 在更年期过渡期出现的水平导致潮热和相关症状。唯一的 FDA批准的潮热疗法是激素疗法（HT）和低剂量形式的帕罗西汀， 一个反间谍组织HT与严重的健康风险有关，包括心脏病，癌症，中风 和痴呆症。帕罗西汀的使用与自杀念头和成瘾有关。虽然没有 其他FDA批准的替代品，医生经常开其他抗抑郁药，抗精神病药， 药物和止痛药，所有这些都有明显的副作用。寻求更少的危险 替代品，许多妇女转向替代疗法，包括营养保健品和针灸， 这些药物在安慰剂对照试验中均未证明有效。一种有效的，非激素， 对于潮热和相关的血管痉挛症状的非抗过敏治疗将是受欢迎的， 新的和有用的治疗方式。MenoGeniX正在重新利用天然存在的人类蛋白质 称为G-CSF治疗潮热，基于安慰剂对照的1期临床试验数据， 表明单次给予G-CSF可以迅速显着减少潮热 频率和严重程度的妇女与自然和生殖诱导绝经。G-CSF良好 耐受性：未报告严重不良事件，不良事件通常为轻度或短期 持续时间，不应影响临床采用。女性更年期也是如此 非洲裔美国女性的反应尤其好。在第1阶段SBIR应用中，我们 申请资金以评估G-CSF每月给药的安全性和有效性（三个单次给药）。 每隔28天注射一次）以治疗绝经期潮热。凭借良好的安全记录， G-CSF可能是不愿意或不能服用HT的女性的一种有价值的替代方案， 帕罗西汀、标签外抗抑郁药、抗精神病药和止痛药，包括阿片类药物。