Effect of Repeated Administration of G-CSF on Hot Flashes and Other Vasomotor Symptoms of Menopause

重复施用 G-CSF 对潮热和更年期其他血管舒缩症状的影响

• 批准号: 9766001
• 负责人: Richard C Duke
• 金额: $ 19.48万
• 依托单位: MENOGENIX, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-15 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9766001
• 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; Cancer Patient; Chest; China; Chronic; Climacteric Arthritis; Clinical; 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; Intellectual Property; Japan; Lead; Legal patent; Licensing; Life; Malignant Neoplasms; Malignant neoplasm of prostate; Manufacturer Name; Menopausal Symptom; Menopause; Methods; Modality; Neck; Neutropenia; Nutraceutical; Operative Surgical Procedures; Paroxetine; Patient Self-Report; Peripheral; Pharmacologic Substance; Pharmacology and Toxicology; Phase; Phase I Clinical Trials; Physicians; Physiological; Placebos; Proteins; Quality of life; Randomized; Risk; Safety; Severities; Skin; Small Business Innovation Research Grant; Stroke; Sweat; Sweating; Symptoms; Vasodilation; Vasomotor; Woman; addiction; aged; base; cardiogenesis; chemotherapy; clinical development; commercialization; hormone therapy; industry partner; malignant breast neoplasm; meetings; novel; off-patent; placebo controlled study; product development; prospective; side effect; subcutaneous; 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. 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 (reddening of the skin). 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 the decreasing hormone levels that occur during the menopause transition lead to increased incidence of hot flashes and related symptoms. The only 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 development of heart disease, cancer, stroke and dementia. Paroxetine use is associated with suicidal thoughts and ideation as well as 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 granulocyte colony-stimulating factor (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 naturally-occurring and surgically-induced menopause. Women with surgically-induced menopause as well as African-American women responded especially well. In this phase 1 SBIR application, MenoGeniX is proposing a placebo- controlled, dose-range finding, phase 2a clinical trial to evaluate the efficacy and safety of G-CSF administered monthly to treat menopausal hot flashes. With a good safety record when used chronically to treat neutropenia, G-CSF may represent a valuable alternative for women with bothersome, moderate to severe hot flashes who are unwilling or unable to take HT or anti-depressants.

更年期最常见和令人痛苦的症状之一是潮热及相关症状。 症状代表着全球范围内未得到满足的重大医疗保健需求，不仅是在手术或手术后的女性中。 自然绝经，也适用于接受激素抑制或激素抑制的乳腺癌和前列腺癌患者 65-90% 的自然绝经女性和大约 7000 万女性会出现潮热。 每年世界各地都有人寻求治疗，潮热通常是一种突然的温暖感觉。 面部、颈部和胸部强烈，周围血管舒张，导致潮红（皮肤变红）。 持续时间各不相同，但平均约为 4 分钟，虽然不是终生出汗。 潮热具有威胁性，会对女性的功能能力和生活质量产生不良影响。 导致潮热发作的生理机制尚不清楚，同样，也不知道它是如何发生的。 更年期过渡期间激素水平下降导致热的发生率增加 潮红和相关症状唯一被批准的治疗方法是激素疗法 (HT) 和激素疗法。 低剂量的帕罗西汀（一种抗抑郁药）会带来严重的健康风险，包括。 心脏病、癌症、中风和痴呆的发生与自杀有关。 虽然没有其他 FDA 批准的替代品，但医生认为。 经常开其他抗抑郁药、抗精神病药和止痛药，所有这些药物都有 为了寻求危险性较小的替代方案，许多女性转向替代疗法。 包括营养保健品和针灸，但这些都没有被证明对安慰剂对照有效 一种有效的、非激素、非抗抑郁药物治疗潮热和相关血管舒缩的药物。 MenoGeniX 正在重新利用一种自然的症状，这将是一种受欢迎、新颖且有用的治疗方式。 人类产生的蛋白质称为粒细胞集落刺激因子（G-CSF），用于治疗潮热 安慰剂对照 1 期临床试验数据表明，单次施用 G-CSF 可导致 快速显着降低女性自然发生的潮热频率和严重程度 手术引起的更年期 手术引起的更年期的女性以及非裔美国人。 在这一 1 期 SBIR 应用中，女性反应特别好，MenoGeniX 提出了一种安慰剂- 受控、剂量范围发现、2a 期临床试验，用于评估 G-CSF 给药的有效性和安全性 每月一次用于治疗更年期潮热，长期用于治疗中性粒细胞减少症具有良好的安全记录， 对于患有令人烦恼的中度至重度潮热的女性来说，G-CSF 可能是一种有价值的替代品。 不愿意或无法服用 HT 或抗抑郁药。