A Study in Subjects With Neurogenic Orthostatic Hypotension

NCT07089043 | Recruiting Phase 2 FDA Drug

• 1 other identifier: CST3056-CLIN-021
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 5

Brief Summary

This is a study to evaluate the effects of CST-3056 on orthostatic symptoms and signs in subjects with neurogenic orthostatic hypotension (nOH).

Conditions

Neurogenic Orthostatic Hypotension

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Standing Systolic Blood Pressure

  Baseline is defined as the pre-dose measurement on Day 1

  Baseline and 1, 2, 3, and 4 hours post-dose on Days 1 to 4

Secondary Outcomes (3)

• Change from Baseline in Seated Systolic Blood Pressure relative to placebo

  Baseline and 5 minutes post-dose on Days 1 to 4

• Change from Baseline in the Orthostatic Hypotension Symptom Assessment (OHSA) Question #1 relative to placebo

  Baseline and 3 hours post-dose on Days 1 to 4

• Change from Baseline in the heads-up tilt table test (HUTT)

  Baseline and 3 hours post-dose on Optimal Dose Day (Day 5)

Study Arms (2)

CST-3056

EXPERIMENTAL

Subjects will receive single doses of CST-3056 over 3 days and on the Optimal Dose Day (Day 5)

Drug: CST-3056

Placebo

PLACEBO COMPARATOR

Subjects will receive a single dose of placebo on 1 day

Drug: Placebo

Interventions

CST-3056 DRUG

Administered as an oral solution

CST-3056

Placebo DRUG

Administered as an oral solution

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects ≥ 18 and ≤ 85 years of age, at time of informed consent.
• Diagnosed with symptomatic orthostatic hypotension due to Parkinson's disease or pure autonomic failure (i.e. neurogenic orthostatic hypotension).
• 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.
• At Screening, subjects must have a score ≥4 on the Orthostatic Hypotension Symptom Assessment (OHSA) scale question #1.
• Currently receiving, or known to be responsive to, direct or indirect α1-AR agonists (e.g., midodrine, droxidopa) for treatment of nOH.
• 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.
• Body weight greater or equal to 50 kg and body mass index (BMI) between 18 and 35 kg/m2, inclusive at Screening.
• Stable medical conditions for 3 months prior to Screening.
• For patients taking antiparkinsonian medication: stable dose of levodopa, dopamine agonist, amantadine, and/or monoamine oxidase B inhibitor, i.e. unchanged for 1 month.
• Subject is ambulatory with/without the use of an assistive device.
• Willing to follow the protocol requirements and comply with protocol restrictions.
• Capable of providing informed consent and complying with study procedures.
• Able to speak, understand, and read English.

You may not qualify if:

• Systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathy of unknown significance, and autoimmune neuropathies.
• 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).
• Supine SBP ≥ 170 mm Hg or seated SBP ≥ 140 mm Hg at Screening.
• 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).
• Concomitant use of anti-hypertensive medication for the treatment of essential hypertension unrelated to autonomic dysfunction.
• 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.
• 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).
• 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.
• History of suicidal ideation or an episode of clinically severe depression as determined by the Investigator.
• 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.
• A calculated eGFR of ≤60 mL/min/1.73m2 according to the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation at Screening.
• Current use of any prohibited prescription medication during Screening or throughout study, unless approved by both the Investigator and the Sponsor Medical Monitor.
• 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.
• Known or suspected alcohol or substance abuse within the past 12 months and/or positive test for alcohol or drugs of abuse at Screening.
• 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).

Sponsors & Collaborators

• CuraSen Therapeutics, Inc.: lead

Study Sites (5)

CuraSen Investigational Site

Scottsdale, Arizona, 85251, United States

RECRUITING

CuraSen Investigational Site

Farmington Hills, Michigan, 48334, United States

RECRUITING

CuraSen Investigational Site

Eatontown, New Jersey, 07724, United States

RECRUITING

CuraSen Investigational Site

New York, New York, 10019, United States

RECRUITING

CuraSen Investigational Site

Nashville, Tennessee, 37240, United States

RECRUITING

Study Officials

• Chief Medical Officer

  CuraSen Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

Chief Medical Officer

CONTACT

650-475-2842; info@curasen.com

Medical Monitor

CONTACT

650-475-2842; info@curasen.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single-blind dose ranging study

Study Record Dates

• First Submitted: July 14, 2025
• First Posted: July 28, 2025
• Study Start: September 12, 2025
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)