A Randomized, Open-label, Multicenter, Phase 2 Clinical Trial to Explore the Safety and Efficacy of Sepranolone in Pediatric and Adult Patients With Tourette Syndrome

The study was an open-label, randomized, multicenter, parallel, Phase 2a study in adolescents and adult patients with Tourette syndrome that aimed to explore the efficacy of Sepranolone as a treatment for Tourette syndrome, by reducing the severity and frequency of tics. The total study duration from the Screening Visit to the final follow-up visit was approximately 26 weeks and included the following periods:
* A baseline period of 4 weeks between the screening visit (Visit 1) and randomization (4 weeks of baseline period were not needed in well-known adult subjects with stable Tourette syndrome history over the past at least 4 weeks). A school holiday/annual leave period of 2-6 weeks where no study-related activities were done.
* A randomized treatment period of 12 weeks
* A safety follow-up period of 4 weeks

开始日期2022-02-16

申办/合作机构

Asarina Pharma AB

NCT04102995

/ Completed临床2期

An Exploratory Phase II, Randomised, Double-blind, Placebo-controlled, Parallel-group Study Investigating the Efficacy and Safety of Sepranolone in Women With Menstrual Migraine

The objective of this phase 2 Proof.of Concept study is to evaluate the efficacy and safety of Sepranolone (UC1010) in preventing menstrual migraine attacks in adult women with migraine occurring between Day -2 and Day 5 of the menstrual cycle. Patients will be taking Sepranolone or Placebo (blinded to patient and study doctor) during the two week preceding the menstruation for three menstrual cycles. Effect (change from baseline) will be assessed by comparison of symptoms recorded daily by the patients using an electronic diary using validated scales for assessment of menstual migraine symptoms.
Sepranolone is identical to an endogenous steroid.

开始日期2019-08-27

申办/合作机构

Asarina Pharma AB

[+1]

NCT03697265

/ Completed临床2期

A Phase II, Randomised, Double-blind, Placebo-controlled, Parallel Group, Multicentre Study Investigating Efficacy and Safety of Sepranolone (UC1010) in Patients With Premenstrual Dysphoric Disorder (PMDD)

The objective of this phase IIb study is to evaluate the effect and safety of Sepranolone (UC1010) on premenstrual symptoms in women with Premenstrual Dysphoric Disorder (PMDD). Patients will be taking Sepranolone or Placebo (blinded to patient and study doctor) during the two weeks preceding the menstruation of three menstrual cycles. Effect (change from baseline) will be assessed by comparison of symptoms recorded daily by the patients using a validated rating scale for assessment of PMDD symptoms. Sepranolone is an endogenous steroid.

开始日期2018-04-20

申办/合作机构

Asarina Pharma AB

[+1]

100 项与 Asarina Pharma AB 相关的临床结果

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0 项与 Asarina Pharma AB 相关的专利（医药）

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项与 Asarina Pharma AB 相关的文献（医药）

2023-06-01·Psychopharmacology

Prefrontal allopregnanolone synergizes with D1 receptor activation to disrupt sensorimotor gating in male Sprague-Dawley rats

Article

作者: Concas, Luca ; Nordkild, Peter ; Bortolato, Marco ; Gaikwad, Nilesh W ; Cadeddu, Roberto ; Frau, Roberto ; Traccis, Francesco ; Mosher, Laura J

RATIONALE:

The prepulse inhibition (PPI) of the startle reflex is the best-established index of sensorimotor gating. We documented that the neurosteroid allopregnanolone (AP) is necessary to reduce PPI in response to D₁ dopamine receptor agonists. Since Sprague-Dawley (SD) rats are poorly sensitive to the PPI-disrupting effects of these drugs, we hypothesized that AP might increase this susceptibility.

OBJECTIVES:

We tested whether AP is sufficient to increase the vulnerability of SD rats to PPI deficits in response to the D₁ receptor full agonist SKF82958.

METHODS:

SD rats were tested for PPI after treatment with SKF82958 (0.05-0.3 mg/kg, SC) in combination with either intraperitoneal (1-10 mg/kg) or intracerebral (0.5 μg/μl/side) AP administration into the medial prefrontal cortex (mPFC) or nucleus accumbens shell. To rule out potential confounds, we measured whether SKF82958 affected the endogenous mPFC levels of AP.

RESULTS:

SD rats exhibited marked PPI deficits in response to the combination of systemic and intra-mPFC AP with SKF82958 but not with the D₂ receptor agonist quinpirole (0.3-0.6 mg/kg, SC). SKF82958 did not elevate mPFC levels of AP but enhanced the content of its precursor progesterone. The PPI deficits caused by SKF82958 in combination with AP were opposed by the AP antagonist isoallopregnanolone (10 mg/kg, IP) and the glutamate NMDA receptor positive modulator CIQ (5 mg/kg, IP).

CONCLUSION:

These results suggest that AP enables the detrimental effects of D₁ receptor activation on sensorimotor gating. AP antagonism or glutamatergic modulation counters these effects and may have therapeutic potential for neuropsychiatric disorders characterized by gating deficits.

2022-11-01·Neurobiology of stress

Acute stress impairs sensorimotor gating via the neurosteroid allopregnanolone in the prefrontal cortex

Article

作者: Cadeddu, Roberto ; Ratto, Gian Michele ; Gaikwad, Nilesh ; Scheggi, Simona ; Bortolato, Marco ; Mosher, Laura J ; Nordkild, Peter

Ample evidence indicates that environmental stress impairs information processing, yet the underlying mechanisms remain partially elusive. We showed that, in several rodent models of psychopathology, the neurosteroid allopregnanolone (AP) reduces the prepulse inhibition (PPI) of the startle, a well-validated index of sensorimotor gating. Since this GABA_A receptor activator is synthesized in response to acute stress, we hypothesized its participation in stress-induced PPI deficits. Systemic AP administration reduced PPI in C57BL/6J mice and Long-Evans, but not Sprague-Dawley rats. These effects were reversed by isoallopregnanolone (isoAP), an endogenous AP antagonist, and the GABA_A receptor antagonist bicuculline and mimicked by AP infusions in the medial prefrontal cortex (mPFC). Building on these findings, we tested AP's implication in the PPI deficits produced by several complementary regimens of acute and short-term stress (footshock, restraint, predator exposure, and sleep deprivation). PPI was reduced by acute footshock, sleep deprivation as well as the combination of restraint and predator exposure in a time- and intensity-dependent fashion. Acute stress increased AP concentrations in the mPFC, and its detrimental effects on PPI were countered by systemic and intra-mPFC administration of isoAP. These results collectively indicate that acute stress impairs PPI by increasing AP content in the mPFC. The confirmation of these mechanisms across distinct animal models and several acute stressors strongly supports the translational value of these findings and warrants future research on the role of AP in information processing.

2020-07-15·Nature reviews. Neurology1区 · 医学

Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: challenges and opportunities

1区 · 医学

Review

作者: Gaudilliere, Brice ; Brenton, Ashley ; Scholz, Joachim ; Burczynski, Michael E ; Angst, Martin S ; Segerdahl, Marta ; Edwards, Robert ; Crean, Christopher ; Pelleymounter, Mary Ann ; Saab, Carl Y ; Mackey, Sean ; Wager, Tor D ; Iyengar, Smriti ; Borsook, David ; Davis, Karen D ; Wasan, Ajay D ; Wang, Jing ; Sang, Christine N ; Tracey, Irene ; Veasley, Christin ; Kong, Jiang-Ti ; Jiang, Yunyun ; Aghaeepour, Nima ; Ahn, Andrew H ; Iadarola, Michael J ; Hergenroeder, Georgene W

Pain medication plays an important role in the treatment of acute and chronic pain conditions, but some drugs, opioids in particular, have been overprescribed or prescribed without adequate safeguards, leading to an alarming rise in medication-related overdose deaths. The NIH Helping to End Addiction Long-term (HEAL) Initiative is a trans-agency effort to provide scientific solutions to stem the opioid crisis. One component of the initiative is to support biomarker discovery and rigorous validation in collaboration with industry leaders to accelerate high-quality clinical research into neurotherapeutics and pain. The use of objective biomarkers and clinical trial end points throughout the drug discovery and development process is crucial to help define pathophysiological subsets of pain, evaluate target engagement of new drugs and predict the analgesic efficacy of new drugs. In 2018, the NIH-led Discovery and Validation of Biomarkers to Develop Non-Addictive Therapeutics for Pain workshop convened scientific leaders from academia, industry, government and patient advocacy groups to discuss progress, challenges, gaps and ideas to facilitate the development of biomarkers and end points for pain. The outcomes of this workshop are outlined in this Consensus Statement.

项与 Asarina Pharma AB 相关的新闻（医药）

2026-03-10

·allsci.com

Relmada Therapeutics raises USD 160m in oversubscribed private placement financing

Relmada Therapeutics (Nasdaq: RLMD), based in Coral Gables, Florida, announced a USD 160 million private placement financing expected to close on or about March 11, 2026, providing capital as the company advances oncology and rare disease programs following the termination of Phase III trials of its former lead depression therapy REL-1017. The PIPE financing was described as oversubscribed. Relmada said the proceeds, together with existing cash, cash equivalents, and short-term investments, will be used for working capital and general corporate purposes, including advancing research and development activities across its pipeline. Under the securities purchase agreement, Relmada is selling 29,474,569 shares of common stock at a purchase price of USD 4.75 per share and pre-funded warrants to purchase 4,210,527 shares of common stock at a purchase price of USD 4.749 per warrant. The pre-funded warrants carry an exercise price of USD 0.001 per share. Fourteen institutional investors participated in the financing, including Venrock Healthcare Capital Partners, Commodore Capital, Janus Henderson Investors, RA Capital Management, Balyasny Asset Management, OrbiMed, Spruce Street Capital, Squadron Capital Management, Columbia Threadneedle Investments, Adage Capital Management, Marshall Wace, Braidwell LP, Great Point Partners, and Eventide Asset Management. Jefferies, Leerink Partners, Piper Sandler, and Mizuho acted as placement agents. The company did not disclose whether insiders participated in the transaction. Company overview and pipeline Relmada Therapeutics is developing therapies for oncology and central nervous system conditions. The company has repositioned its pipeline following the discontinuation of Phase III development of REL-1017 (esmethadone), an NMDA receptor antagonist that had been evaluated for major depressive disorder. Several Phase III studies of REL-1017 had used change from baseline in MADRS10 total score as the primary endpoint. The company’s current pipeline centers on NDV-01, an intravesical formulation of gemcitabine and docetaxel being developed for non-muscle invasive bladder cancer. A Phase II single-arm study of NDV-01 in high-grade NMIBC is currently recruiting in Israel with an estimated enrollment of 70 patients. A Phase III registration-track study in intermediate-risk NMIBC with an estimated enrollment of 302 patients is planned to begin in May 2026, with disease-free survival as a primary endpoint. Relmada expanded its CNS pipeline in February 2025 through the acquisition of sepranolone from Asarina Pharma for USD 3 million. Sepranolone is a GABA-A modulating steroid antagonist under development for Tourette syndrome, Prader-Willi syndrome, essential tremor, and other compulsivity-related disorders. The company has stated that a Phase II study of sepranolone in Prader-Willi syndrome is planned for the first half of 2026. In addition to these programs, Relmada holds rights outside Asia to a psilocybin and derivatives program acquired from Arbormentis LLC in 2021 for USD 15 million in upfront consideration consisting of cash and equity. The financing announced this week is expected to support development activities across these programs as Relmada advances new clinical studies in oncology and CNS disorders. Leave a Reply Cancel reply Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

临床2期临床3期并购

2025-07-16

·生物制药小编

效果不如安慰剂，公司选择退货

在经历了三次的临床失败之后，Relmada Therapeutics最终放弃了其引进REL-1017的开发权益。这项授权协议最早是在2018年1月签订，授权方是康奈尔大学的两位医学博士Charles Inturrisi、Paolo Manfredi。价格相当便宜，首付款只有18万美元，不过，这个授权协议特殊的一点在于—该授权交易的后续付款，即，Relmada需每三个月向Inturrisi和Manfredi支付4.5万美元，直到REL-1017上市销售或专利到期为止。现在，REL-1017实现获批上市销售不可能达到了，Relmada再不选择终止协议，就等于白白送钱了。安慰剂效果太好？REL-1017是一款NMDA受体通道阻断剂，旨在优先靶向过度活跃的GluN1-GluN2D NMDAR通道，阻止过量钙离子进入神经元内，同时维持生理性谷氨酸能神经传递，恢复神经元回路。作为唯一一条管线，REL-1017曾备受Relmada倚重。2019年10月，REL-1017治疗重度抑郁症的II期临床大获成功，使公司股价大涨了134%，因此备受关注。然而，REL-1017进入III期临床后不断失利。2022年10月， Relmada宣布，REL-1017作为重度抑郁症（MDD）单药治疗的III期临床RELIANCE III未能达到主要终点，相比安慰剂，REL-1017的MADRS10评分未能达到显著改善（-14.8分 vs -13.9分）。这一消息令投资者对此十分失望，受此消息影响，当日公司股价暴跌近78%。然而，打击接踵而至，两个月后，Relmada就再次报告了REL-1017临床失败的消息。2022年12月，Relmada宣布，REL-1017作为重度抑郁症（MDD）辅助治疗的III期RELIANCE-I也未能达到试验主要终点。相比慰剂组，REL-1017组患者的MADRS评分没有得到显著改善（-15.1分 vs -12.9分），公司股价跌去40%。并且更不好的信号是，RELIANCE-III和RELIANCE-I的某些试验站点都出现了安慰剂的效果显著优于REL-1017的情况。除了临床令人所望之外，Relmada关于该项临床失败的事后解释也让外界对其观感变差。关于两项临床失败，Relmada将其解释为“安慰剂效果太好”，因此，Relmada还进行了一个事后分析：专门剔除了安慰剂组过高或过低的数据，使得REL-1017组的MADRS评分相比安慰剂组达到了显著差异。即便如此，也还是没能扭转REL-1017的命运。到2024年12月，经独立数据监测委员会（DMC）分析，认为其RELIANCE II试验不太可能达到主要终点。这一结论令Relmada彻底失去希望，随即，Relmada终止了该项临床试验，并连同另一项临床方案相似的临床试验RELIGHT。同步的，Relmada宣布了寻求其他战略方案，包括合并或出售公司。用迷幻药来减肥？除了对REL-1017临床失败进行强行解释之外，Relmada还有一些迷惑操作。或许是为了防止对REL-1017的过度依赖。在2021年，Relmada从Arbormentis公司引进了其裸盖菇素及其衍生物项目（REL-P11）的开发和商业化权利，首付款1500万美元（现金+股权），潜在里程碑付款约为1.5亿美元。裸盖菇素，因为被发现在抑郁症和焦虑症的治疗中具有明显疗效，近年来，重点被开发用于精神疾病治疗。但这家公司不走寻常路，将REL-P11（低剂量缓释型裸盖菇素）开发用于治疗肥胖症在内的代谢性疾病。Relmada还成功的将其推进到临床Ⅰ期阶段。但现在已经被暂停开发了。在公司2024的财报中，REL-P11就被列为重新评估对象，目前，已经被暂停开发了。原因是认为减肥领域竞争太激烈，以及迷幻药监管批准较为严格等。目前，Relmada的战略重心是剩下的两条管线NDV-01和Sepranolone。NDV-01是一种吉西他滨和多西他赛复方缓释制剂，用于治疗非肌层浸润性膀胱癌（NMIBC），目前处于临床Ⅱ期阶段。Sepranolone是一种GABA-A调节类固醇拮抗剂，2025年2月从Asarina Pharma获得许可，目前处于临床Ⅱb期阶段。就现金情况看来，现在要推进这两条管线的开发也相当具有挑战性。据该公司2025年一季度财报，截止2025年3月31日，公司现金、现金等价物和短期投资约为2710万美元。参考出处：https://www.relmada.com/for-investors/news/detail/318/relmada-therapeutics-reports-first-quarter-2025-financialhttps://www.fiercebiotech.com/biotech/relmada-terminates-license-agreement-troubled-phase-3-depression-assethttps://www.sec.gov/Archives/edgar/data/1553643/000121390018000707/f8k011618ex10-1_relmada.htmhttps://www.fiercebiotech.com/biotech/relmada-reconsiders-plans-test-magic-mushroom-extract-obesity#:~:text=At%20the%20time,as%20part%20of%20our%20prioritization%20efforts

临床3期引进/卖出临床2期临床失败临床结果

2025-07-11

·FierceBiotech

Relmada terminates license agreement for troubled phase 3 depression asset

Relmada originally licensed esmethadone in 2018 for $180,000 upfront and subsequent payments of $45,000 every three months.\n After prematurely ending two phase 3 depression trials last year, Relmada Therapeutics has formally given up on the asset they were testing. The Florida-based biotech terminated its license agreement for esmethadone on July 7, with all of their obligations under the deal set to expire on Oct. 5.Relmada has tested esmethadone, which it called REL-1017, in several phase 3 trials for various major depressive disorder (MDD) indications. The prospect flopped in just about every one of them.In October 2022, REL-1017 failed to top placebo as an MDD monotherapy in the phase 3 RELIANCE III trial. Another stumble followed just months later, this time as an adjunctive MDD treatment in late-stage RELIANCE I, which the company attributed to “a limited number of high-enrolling sites with unplausible placebo response.”Esmethadone did better in a 2023 open-label trial, successfully improving depression symptoms, but the study had no placebo arm.The third phase 3 strike for REL-1017 came in December 2024, when Relmada revealed that its RELIANCE II trial, which was testing esmethadone as an adjunctive treatment for MDD, was unlikely to hit its primary endpoint. As a result, Relmada scrapped the trial and another related study, RELIGHT, which used a similar design, and announced plans to pursue strategic alternatives like a merger or sale of the company.Esmethadone is a component of methadone, the pain and substance use medication. Relmada originally licensed the candidate in January 2018 from Charles Inturrisi, Ph.D., and Paolo Manfredi, M.D., for an upfront fee of $180,000. Inturrisi, a pharmacologist at Cornell University, originally developed esmethadone and licensed it to Medeor, which Manfredi co-founded. Relmada merged with Medeor in 2013.Manfredi’s Medeor is not to be confused with kidney transplant company Medeor Therapeutics. As part of the licensing deal, Relmada was paying Inturrisi and Manfredi $45,000 every three months, a stipulation that was set to continue until esmethadone was sold as a commercial product or the patent on it expired.Relmada is now focused on making strategic asset acquisitions, according to its website, as well as advancing remaining assets NDV-01 and sepranolone. NDV-01 is currently being tested in an open-label phase 2 trial in non-muscle invasive bladder cancer, while sepranolone is a phase 2 Tourette syndrome asset that Relmada purchased in February from Asarina Pharma.