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

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 2

Conditions: Postural Orthostatic Tachycardia Syndrome (POTS)

Treatments: Drug: REGN7544; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06593600

R7544-POTS-2429

Details and patient eligibility

About

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)

Enrollment: 81 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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81 participants in 3 patient groups, including a placebo group

Low Dose

Experimental group

Description:

Randomized 1:1:1

Treatment:

Drug: REGN7544

High Dose

Experimental group

Description:

Randomized 1:1:1

Treatment:

Drug: REGN7544

Matching Placebo

Placebo Comparator group

Description:

Randomized 1:1:1

Treatment:

Drug: Placebo