CST-3056 for neurogenic orthostatic hypotension

A Single-Blind Dose-Ranging Study in Subjects With Neurogenic Orthostatic Hypotension to Evaluate the Effect of CST-3056 on Symptoms and Signs of Orthostatic Hypotension

CST-3056 is being tested to see if it reduces dizziness and low blood pressure when standing in adults with neurogenic orthostatic hypotension.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: CuraSen Therapeutics, Inc. (Industry-sponsored)
• Locations: 5 sites (Scottsdale, Arizona and 4 other locations)
• Trial ID: NCT07089043 on ClinicalTrials.gov

What this trial studies

This single-blind, dose-ranging Phase 2 trial gives single oral doses of CST-3056 once daily for five days to adults with neurogenic orthostatic hypotension, with placebo control. Subjects must stop other direct or indirect α1-AR agonists for a washout period before screening and before starting study drug. The individual optimal dose for each participant is chosen from observations on Days 1–4 based on standing blood pressure and tolerability, and the chosen dose is given again on Day 5. Safety is monitored during the inpatient stay and by a follow-up phone call 3–7 days after discharge.

Who should consider this trial

Good fit: Adults aged 18–85 with symptomatic neurogenic orthostatic hypotension due to Parkinson's disease or pure autonomic failure who meet the diagnostic BP drop and have responded to or currently use α1-AR agonists are ideal candidates.

Not a fit: Patients without a neurogenic cause of orthostatic hypotension, those not responsive to α1-AR agonists, people unable to safely stop their current nOH medications, or those outside the age range are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, CST-3056 could reduce orthostatic symptoms and improve standing blood pressure, which may lower the risk of falls and improve daily function.

How similar studies have performed: Approved agents like midodrine and droxidopa, which act on similar pathways, have shown symptom improvement in nOH, but CST-3056 itself is a novel agent with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

1. Male or female subjects ≥ 18 and ≤ 85 years of age, at time of informed consent.
2. Diagnosed with symptomatic orthostatic hypotension due to Parkinson's disease or pure autonomic failure (i.e. neurogenic orthostatic hypotension).
3. At Screening, subjects must meet the diagnostic criteria of neurogenic orthostatic hypotension, as demonstrated by a decrease ≥20 mm Hg in systolic or ≥10 mm Hg in diastolic BP upon standing ≤3 minutes from a supine position.
4. At Screening, subjects must have a score ≥4 on the Orthostatic Hypotension Symptom Assessment (OHSA) scale question #1.
5. Currently receiving, or known to be responsive to, direct or indirect α1-AR agonists (e.g., midodrine, droxidopa) for treatment of nOH.
6. If the Investigator determines that additional autonomic function testing is required to confirm the diagnosis of autonomic dysfunction, the Valsalva maneuver may be performed to show the absence of BP overshoot during phase IV.
7. Body weight greater or equal to 50 kg and body mass index (BMI) between 18 and 35 kg/m2, inclusive at Screening.
8. Stable medical conditions for 3 months prior to Screening.
9. For patients taking antiparkinsonian medication: stable dose of levodopa, dopamine agonist, amantadine, and/or monoamine oxidase B inhibitor, i.e. unchanged for 1 month.
10. Subject is ambulatory with/without the use of an assistive device.
11. Willing to follow the protocol requirements and comply with protocol restrictions.
12. Capable of providing informed consent and complying with study procedures.
13. Able to speak, understand, and read English.

Exclusion Criteria:

1. Systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathy of unknown significance, and autoimmune neuropathies.
2. Concomitant use of vasoconstricting agents for the purpose of increasing blood pressure (BP) such as ephedrine, dihydroergotamine, or midodrine must be stopped at least 1 day or 5 half-lives (whichever is longer) prior to dosing on Day 1 and throughout the duration of the study. Fludrocortisone use in the study will be limited to a stable dose of 0.1 mg once-daily (QD).
3. Supine SBP ≥ 170 mm Hg or seated SBP ≥ 140 mm Hg at Screening.
4. Subjects with clinically meaningful urinary retention who use or are likely to use α1-AR antagonists (e.g., tamsulosin \[Flomax\]), or other medications (e.g., trazodone).
5. Concomitant use of anti-hypertensive medication for the treatment of essential hypertension unrelated to autonomic dysfunction.
6. Evidence of any significant or unstable clinical disorder or laboratory finding that renders the subject unsuitable for receiving an investigational drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, gastrointestinal, endocrine (excluding managed hypo and hyperthyroidism), metabolic, renal, or other systemic disease or laboratory abnormality.
7. History of malignant disease within 5 years, including solid tumors and hematologic malignancies (except \[a\] basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured; \[b\] low-grade adenocarcinoma of the prostate).
8. Any clinically significant illness or disease (apart from those typically associated with neurodegenerative disease) as determined by medical and surgical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory assessments conducted at Screening.
9. History of suicidal ideation or an episode of clinically severe depression as determined by the Investigator.
10. Clinically significant abnormalities of ECG, including QTcF \> 450 ms, for males and QTcF \> 470 ms for females, and/or HR \< 50 beats per minute, or evidence of clinically significant bundle branch blocks, as indicated by 12-lead ECG in a supine position at Screening.
11. A calculated eGFR of ≤60 mL/min/1.73m2 according to the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation at Screening.
12. Current use of any prohibited prescription medication during Screening or throughout study, unless approved by both the Investigator and the Sponsor Medical Monitor.
13. Prior treatment with any investigational drug ≤90 days prior to dosing (Day 1), or ≤5 half-lives of the drug (whichever is longer), or current enrollment in any other study treatment or disease study, except for observational studies.
14. Known or suspected alcohol or substance abuse within the past 12 months and/or positive test for alcohol or drugs of abuse at Screening.
15. Positive screening test for human immunodeficiency virus (HIV), hepatitis C antibody (HCV Ab) or current hepatitis B infection (defined as positive for hepatitis B surface antigen \[HbsAg\] at Screening).
16. Females who are breastfeeding.
17. Any other reason for which the Investigator considers it is not in the best interest of the subject to undertake the study.

Where this trial is running

Scottsdale, Arizona and 4 other locations

• CuraSen Investigational Site — Scottsdale, Arizona, United States (Recruiting)
• CuraSen Investigational Site — Farmington Hills, Michigan, United States (Recruiting)
• CuraSen Investigational Site — Eatontown, New Jersey, United States (Recruiting)
• CuraSen Investigational Site — New York, New York, United States (Recruiting)
• CuraSen Investigational Site — Nashville, Tennessee, United States (Recruiting)

Study contacts

• Study coordinator: Chief Medical Officer

Conditions Neurogenic Orthostatic Hypotension