NCT05696717进行中（未招募）3 期
A Phase 3, Multi-center, Randomized Withdrawal and Long Term Extension Study of Ampreloxetine for the Treatment of Symptomatic Neurogenic Orthostatic Hypotension in Participants With Multiple System Atrophy
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 102
- 试验地点
- 77
- 主要终点
- Change in OHSA composite score at Week 8 during the double-blind RW period
研究概览
简要总结
This is a Phase 3, multi-center, randomized withdrawal study to evaluate the efficacy and durability of ampreloxetine in participants with MSA and symptomatic nOH after 20 weeks of treatment. This study includes 4 periods: Screening, open label, randomized withdrawal, and long-term treatment extension (LTE).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant is male or female and at least 30 years old.
- •Participant has a diagnosis of possible or probable MSA of the Parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) according to The Gilman Criteria (2008).
- •Participant has a diagnosis of possible or probable MSA of the Parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) confirmed by the Enrollment Steering Committee (ESC).
- •Participant must meet the diagnostic criteria of nOH, as demonstrated by a sustained reduction in BP of ≥20 mmHg (systolic) or ≥10 mmHg (diastolic) within 3 min of standing as part of orthostatic standing test or being tilted up ≥60o from a supine position as determined by a tilt-table test.
- •Participant must score ≤4 on UMSARS Part IV at Visit 1 (Screening).
- •Participant must score at least a 4 on the OHSA item 1 at Visit 2 (Day 1).
- •Participant must be willing to not take any prohibited medications during the study.
- •If participant is female, the participant must not be pregnant, breastfeeding, or planning a pregnancy during the course of the study. A woman of childbearing potential must have a documented negative pregnancy test at screening.
- •During the study and for 30 days after receiving the last dose of the study drug, females of childbearing potential or males capable of fathering children must agree to use highly effective birth control measures (failure rate <1% when used consistently and correctly) or agree to abstain from sexual intercourse.
- •Participant is willing and able to provide signed and dated written informed consent to -participate prior to initiation of any study related procedures.
- •Participant is able to communicate well with the Investigator and clinic staff, understands the expectations of the study and is able to comply with the study procedures, requirements, and restrictions.
排除标准
- •Participant has a systemic illness known to produce autonomic neuropathy, including, but not limited to, amyloidosis and autoimmune neuropathies. Participant with diabetes mellitus (DM) will be evaluated on a case-by-case basis by the medical monitor and considered ineligible unless they meet all of the following criteria:
- •Well controlled type-2 DM in treatment with only oral medications and diet
- •HbA1C of ≤7.5% performed during screening or up to 12 weeks before screening
- •No clinically evident peripheral neuropathy (e.g., normal sensory examination on peripheral extremities)
- •No known retinopathy (e.g., annual ophthalmic exam is sufficient)
- •No nephropathy (e.g., absence of albuminuria and GFR >60).
- •Participant has a known intolerance to other NRIs or SNRIs.
- •Participant currently uses concomitant antihypertensive medication for the treatment of essential hypertension.
- •Participant has used strong CYP1A2 inhibitors or inducers within 7 days or 5 half lives, whichever is longer, prior to Visit 2 (Day 1) or requires concomitant use until the Safety follow-up Visit.
- •Participant has changed dose, frequency, or type of prescribed medication for orthostatic hypotension within 7 days prior to Visit 2 (Day 1).
- •Midodrine and droxidopa (if applicable) must be tapered off and stopped at least 7 days prior to Visit 2 (Day 1).
- •Participant has known or suspected alcohol or substance abuse within the past 12 months (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision [DSM IV TR®] definition of alcohol or substance abuse).
- •Participant has clinically unstable coronary artery disease or had a major cardiovascular event (e.g., myocardial infarction) in the past 6 months.
- •Participant has significant uncontrolled cardiac arrhythmia, history of complete heart block, or significant QTc prolongation (≥450 msec for males and ≥470 msec for females).
- •Participant has a new onset of a neurological event (i.e., seizures, confusion, altered levels of consciousness, etc.) in the past 6 months.
- •Participant has used any monoamine oxidase inhibitor (MAOI) within 14 days prior to Visit 2 (Day 1).
- •Participant has a history of untreated closed angle glaucoma, or treated closed angle glaucoma that, in the opinion of an ophthalmologist, might result in an increased risk to the participant.
- •Participant has a Montreal Cognitive Assessment (MoCA) <
- •Participant is unable or unwilling to complete all protocol specified procedures including questionnaires.
- •Participant has known congestive heart failure (New York Heart Association [NYHA] Class 3 or 4).
- •Participant has had any malignant disease, other than carcinoma in situ of the cervix or basal cell carcinoma, within the past 2 years prior to Screening.
- •Participant has a known gastrointestinal (GI) condition, which in the Investigator's judgment, may affect the absorption of study medication (e.g., ulcerative colitis, gastric bypass).
- •Participant has psychiatric, neurological, or behavioral disorders that may interfere with the cognitive ability of the participant to give informed consent, understand and comply with study procedures, or interfere with the conduct of the study.
- •Participant is currently receiving any investigational drug or has received an investigational drug within 30 days of dosing. An investigational drug is defined as a drug that is not approved by a regulatory agency (e.g., Food and Drug Administration [FDA]).
- •Participant has a clinically significant abnormal laboratory finding(s) (e.g., alanine aminotransferase [ALT] or aspartate aminotransferase [AST] ≥3.0 x upper limit of normal [ULN]; blood bilirubin [total] ≥3.0 x ULN; estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, or any abnormal laboratory value that could interfere with safety of the participant).
- •Participant has demonstrated lifetime suicidal ideation and/or suicidal behavior, as outlined by the C-SSRS (Baseline/Screening Version). Participant should be assessed by the rater for risk of suicide and the participant's appropriateness for inclusion in the study.
- •Participant has a concurrent disease or condition (e.g., COVID-19), or recent surgery, that in the opinion of the Investigator, would confound or interfere with study participation or evaluation of safety, tolerability, or absorption of the study drug.
- •Participant has known hypersensitivity to ampreloxetine (ampreloxetine hydrochloride), or any excipients in the formulation.
- •Major surgery (i.e., procedures involving higher risk for infection and extended recovery period, such as, joint replacement, gastric bypass, open heart surgery, organ transplant, etc.) occurring less than 4 weeks prior to enrollment.
研究组 & 干预措施
Ampreloxetine (Randomized Withdrawal)
Placebo Comparator
After completing the open label, participants are randomized to either ampreloxetine or placebo receiving a single, oral, daily dose of active drug or placebo for a further 8 weeks.
干预措施: Ampreloxetine (Drug)
Ampreloxetine (Open Label)
Active Comparator
Participants will receive ampreloxetine as a single, oral, daily dose of active drug for 12 weeks.
干预措施: Ampreloxetine (Drug)
Ampreloxetine (Randomized Withdrawal)
Placebo Comparator
After completing the open label, participants are randomized to either ampreloxetine or placebo receiving a single, oral, daily dose of active drug or placebo for a further 8 weeks.
干预措施: Placebo (Drug)
Long-Term Extension Period
Active Comparator
Participants will receive ampreloxetine as a single, oral, daily dose of active drug for 104 weeks.
干预措施: Ampreloxetine (Drug)
结局指标
主要结局
Change in OHSA composite score at Week 8 during the double-blind RW period
时间窗: 8-week randomized withdrawal period (Week 12 to Week 20)
Score change from baseline on the composite of Questions 1 - 6 of the Orthostatic Hypotension Symptom Assessment (OHSA).
次要结局
- Change from baseline in OHDAS item 1 (activities that require standing for a short time) at Week 8 post randomization(8-week randomized withdrawal period (Week 12 to Week 20))
- Change from baseline in OHDAS item 3 (activities that require walking for a short time) at Week 8 post randomization(8-week randomized withdrawal period (Week 12 to Week 20))
研究者
研究点 (77)
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相关资讯
Theravance Biopharma's Phase 3 CYPRESS Study Fails Primary Endpoint, Company Winds Down Ampreloxetine Program- Theravance Biopharma's Phase 3 CYPRESS study evaluating ampreloxetine for neurogenic orthostatic hypotension in multiple system atrophy patients failed to meet its primary endpoint, leading to program termination.
- The company is implementing a 60% cost reduction through organizational restructuring, including complete R&D wind-down and 50% workforce reduction, expected to save approximately $70 million annually.
- Theravance's Strategic Review Committee is accelerating evaluation of value-maximizing alternatives, including potential company sale, while focusing on YUPELRI as its core commercial asset.
- With $400 million expected cash at Q1 2026 end and projected $60-70 million annual cash flow from YUPELRI, the company maintains strong financial position despite clinical setback.6 months agoTheravance Biopharma Completes Phase 3 Enrollment for Ampreloxetine in Rare Neurological Disorder- Theravance Biopharma has completed enrollment in the pivotal Phase 3 CYPRESS study of ampreloxetine for neurogenic orthostatic hypotension in multiple system atrophy patients.
- The investigational once-daily norepinephrine reuptake inhibitor could become the first therapy to provide durable benefit for 40,000 U.S. patients with this devastating condition.
- Topline results are expected in Q1 2026, with plans for expedited NDA submission and priority FDA review if data prove supportive.
- Previous Study 0170 showed a 72% reduction in treatment failure odds for MSA patients, demonstrating compelling symptom improvement without worsening supine hypertension.last yearChina Approves First Once-Daily Nebulized LAMA for COPD, Triggering $7.5M Milestone for Theravance- China's NMPA has approved YUPELRI (revefenacin) as the first once-daily nebulized long-acting muscarinic antagonist for maintenance treatment of chronic obstructive pulmonary disease.
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- The approval strengthens Theravance's financial position, which includes $131 million in cash and potential near-term milestone payments from multiple revenue streams.last yearAmpreloxetine Shows Promise for Neurogenic Orthostatic Hypotension in MSA Patients Without Worsening Supine Hypertension- New analyses from Theravance Biopharma's Phase 3 trials demonstrate ampreloxetine's selective mechanism of action and durable target engagement in treating neurogenic orthostatic hypotension (nOH) in multiple system atrophy patients.
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