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Completed

NCT Number: NCT06593600

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

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) * How the study drug affects symptoms associated with POTS

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Key information

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Calgary, Calgary, Alberta, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Is diagnosed with POTS and demonstrates consensus criteria (a), (b), (c) and (d) below during screening:
  • Increase in HR ≥30 Beats Per Minute (BPM) within 10 minutes of changing from supine to a standing position, as described in the protocol
  • Absence of orthostatic hypotension, defined as a decrease in Systolic Blood Pressure (SBP) >20 mm Hg within 3 minutes of standing
  • Absence of other conditions explaining orthostatic tachycardia in the judgment of the investigator, as defined in the protocol
  • 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
  • During screening, a participant must score ≥3 on the Patient Global Impressions of Severity (PGIS)
  • Has a body mass index between 18 and 35 kg/m2, inclusive

Key Exclusion Criteria:

  • History of hypertension or a seated SBP during screening that is >140 mm Hg
  • SBP during Active Stand (AS) test during screening, either supine or standing, that is >140 mm Hg systolic on ≥2 measurements
  • Increase in HR <20 BPM within 10 minutes of changing from supine to a standing position, as defined in protocol
  • 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
  • Is confined to bed more than 50% of waking hours
  • 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

Treatment and study plan

REGN7544

Drug

Subcutaneous (SC) administration

Other names: baloncibart

Placebo

Drug

SC administration

Primary outcomes

  1. Change in Heart Rate (HR) from supine to standing (DeltaHR)

    Time frame: At Day 8

  2. Change from baseline in DeltaHR-avg

    Time frame: At day 29

    Only for Cohort B

Secondary outcomes

  1. Occurrence of Treatment-Emergent Adverse Events (TEAEs)

    Time frame: Through 90 Days

  2. Severity of TEAEs

    Time frame: Through 90 Days

  3. DeltaHR

    Time frame: At Day 15 and 29

  4. Supine HR

    Time frame: At Day 8, 15, and 29

  5. Standing HR

    Time frame: At Day 8, 15, and 29

  6. Supine blood pressure (BP)

    Time frame: At Day 8, 15, and 29

  7. Standing BP

    Time frame: At Day 8, 15, and 29

  8. Concentrations of REGN7544 in serum

    Time frame: Through 90 Days

  9. Occurrence of anti-drug antibodies (ADAs) to REGN7544

    Time frame: Through 90 Days

  10. Magnitude of ADAs to REGN7544

    Time frame: Through 90 Days

  11. Change from baseline in Orthostatic Symptom Domain Scores of the Living with POTS Questionnaire (LWPQ)

    Time frame: At day 29

    Only for Cohort B

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: PINNACLE

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Sep 19, 2024
Registry last updated
Jul 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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