Clinical trial NCT06593600: Study of Natriuretic Peptide Receptor 1 (NPR1) Antagonist in Adult Patients With Postural Orthostatic Tachycardia Syndrome (POTS)
Official title: A Phase 2 Double-Blind Placebo-Controlled Single-Dose Study of Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of REGN7544, an NPR1 Antagonist Monoclonal Antibody, in Patients With Postural Orthostatic Tachycardia Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Postural Orthostatic Tachycardia Syndrome (POTS)
Keywords: Orthostatic intolerance
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is researching an experimental drug called REGN7544 (called "study drug"). The study is focused on participants with POTS.

The aim of the study is to see how safe, tolerable, and effective the study drug is.

The study is looking at several other research questions, including:

* How the study drug changes heart rate and blood pressure in participants with POTS
* What side effects may happen from taking the study drug
* How much study drug is in the blood at different times
* Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects)


Eligibility criteria: Key Inclusion Criteria:

1. Is diagnosed with POTS and demonstrates consensus criteria (a), (b), (c) and (d) below during screening:

   1. Increase in HR ≥30 beats per minute (BPM) within 10 minutes of changing from supine to a standing position, as described in the protocol
   2. Absence of orthostatic hypotension, defined as a decrease in systolic blood pressure (SBP) \>20 mm Hg within 3 minutes of standing
   3. Absence of other conditions explaining orthostatic tachycardia in the judgment of the investigator, as defined in the protocol
   4. Ongoing episodic symptoms consistent with POTS (for example, lightheadedness, palpitations, tremulousness, generalized weakness, blurred vision, and fatigue) that are worse with standing and are relieved by lying down and which have been present for ≥3 months
2. During screening, a participant must score ≥3 on the Patient Global Impressions of Severity (PGIS)
3. Has a body mass index between 18 and 35 kg/m2, inclusive

Key Exclusion Criteria:

1. History of hypertension or a seated SBP during screening that is \>140 mm Hg
2. SBP during active stand (AS) test during screening, either supine or standing, that is \>140 mm Hg systolic on ≥2 measurements
3. Increase in HR \<20 BPM within 10 minutes of changing from supine to a standing position, as defined in protocol
4. Is judged by the investigator to have significant heart failure, cardiovascular disease, liver disease, or renal disease (ie, estimated glomerular filtration rate (eGFR) \<60 ml/min/1.73m2) based on medical history, physical exam, laboratory studies, and/or electrocardiogram (ECG) performed during screening period
5. Is confined to bed more than 50% of waking hours
6. Within 5 days of screening visit has used medications with direct effects on blood volume, BP, or HR (eg, midodrine, droxidopa, octreotide, clonidine, methyldopa, ivabradine, beta-blockers, calcium channel blockers, pyridostigmine, fludrocortisone, desmopressin, stimulants or intravenous (IV) saline)

NOTE: Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Change in Heart Rate (HR) from supine to standing (DeltaHR)
timeFrame: At Day 8
Secondary outcomes:
measure: Occurrence of Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Through 90 Days
measure: Severity of TEAEs
timeFrame: Through 90 Days
measure: DeltaHR
timeFrame: At Day 15 and 29
measure: Supine HR
timeFrame: At Day 8, 15, and 29
measure: Standing HR
timeFrame: At Day 8, 15, and 29
measure: Supine blood pressure (BP)
timeFrame: At Day 8, 15, and 29
measure: Standing BP
timeFrame: At Day 8, 15, and 29
measure: Concentrations of REGN7544 in serum
timeFrame: Through 90 Days
measure: Incidence of anti-drug antibodies (ADAs) to REGN7544
timeFrame: Through 90 Days
measure: Titer of ADAs to REGN7544
timeFrame: Through 90 Days
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Mercy Gilbert Medical Center
state: Arizona
city: Carlsbad
country: United States
facility: North County Neurology Associates
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Pasadena
country: United States
facility: Southern California Heart Specialists
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Clearwater
country: United States
facility: Innovative Research of West Florida, Inc.
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Health Neuroscience Center
state: Indiana
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's MidAmerica Heart Institute
state: Missouri
city: New York
country: United States
facility: New York University Langone
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: