Study of Natriuretic Peptide Receptor 1 (NPR1) Antagonist in Adult Patients With Postural Orthostatic Tachycardia Syndrome (POTS) (PINNACLE)

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

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Postural Orthostatic Tachycardia Syndrome (POTS)
• Intervention / Treatment: Drug: Placebo; Drug: REGN7544

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85297
      • Mercy Gilbert Medical Center
  • California
    • Carlsbad, California, United States, 92011
      • North County Neurology Associates
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Pasadena, California, United States, 91105
      • Southern California Heart Specialists
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Neuroscience Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's MidAmerica Heart Institute
  • New York
    • New York, New York, United States, 10016
      • New York University Langone
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose; Randomized 1:1:1	Drug: REGN7544; Subcutaneous (SC) administration
Experimental: High Dose; Randomized 1:1:1	Drug: REGN7544; Subcutaneous (SC) administration
Placebo Comparator: Matching Placebo; Randomized 1:1:1	Drug: Placebo; SC administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Heart Rate (HR) from supine to standing (DeltaHR)	At Day 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Concentrations of REGN7544 in serum	Through 90 Days
Occurrence of Treatment-Emergent Adverse Events (TEAEs)	Through 90 Days
Severity of TEAEs	Through 90 Days
DeltaHR	At Day 15 and 29
Supine HR	At Day 8, 15, and 29
Standing HR	At Day 8, 15, and 29
Supine blood pressure (BP)	At Day 8, 15, and 29
Standing BP	At Day 8, 15, and 29
Incidence of anti-drug antibodies (ADAs) to REGN7544	Through 90 Days
Titer of ADAs to REGN7544	Through 90 Days

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

Helpful Links

• Study Informational Website

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2024
• Primary Completion (Actual): April 13, 2026
• Study Completion (Estimated): July 6, 2026

Study Registration Dates

• First Submitted: September 9, 2024
• First Submitted That Met QC Criteria: September 9, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Orthostatic intolerance
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Orthostatic Intolerance; Postural Orthostatic Tachycardia Syndrome; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: R7544-POTS-2429

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No