An Efficacy, Safety, Tolerability and Dose Finding Study of XXB750 in Resistant Hypertension Patients.

NCT05562934 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CXXB750B122012021-005738-41
• Study Type: interventional
• Target: 189
• Locations: 15 countries
• Sites: 76

Brief Summary

The purpose of this 20-week randomized double-blind study in patients with resistant hypertension (rHTN) is to evaluate the efficacy, safety, and tolerability, of different doses of XXB750 administered as subcutaneous (SC) injections, compared to placebo. Since all study participants will be patients with rHTN, all study treatments will be given on top of maximally tolerated background antihypertensive therapy recommended by international guidelines for treatment of HTN (i.e., a thiazide or a thiazide-like diuretic, an angiotensin converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB), and a long-acting dihydropyridine calcium channel blocker (CCB).

Conditions

Resistant Hypertension

Keywords

hypertension; resistant hypertension; rHTN; not controlled hypertension

Outcome Measures

Primary Outcomes (1)

• Dose-response (DR) Relationship of XXB750 With Respect to Change From Baseline in Systolic Blood Pressure (SBP) 24 Hours

  To evaluate the efficacy and dose-response relationship of different doses of XXB750 compared to placebo in reducing the mean 24 hours ambulatory systolic blood pressure from baseline at Week 12. Automated arterial BP determinations and pulse rate readings were made with Microlife Watch BP Office 2G, an automated digital BP device. The primary outcome measure was evaluated using an optimally weighted contrast test following the Multiple Comparison Procedure-Modeling (MCP-MOD) methodology. There were five candidate models to capture the shape of the dose-response relationship for XXB750 at Week 12 endpoint. The outcome for the single best candidate model is shown in the Statistical Analysis section.

  Baseline, Week 12

Secondary Outcomes (3)

• Change From Baseline in SBP 24 Hours at Week 12 (Difference Between Highest XXB750 Dose and Placebo)

  Baseline, Week 12

• Change From Baseline in SBP 24 Hours of Average of Week 9 and Week 12 (Difference Between Highest XXB750 Dose and Placebo)

  Baseline, Week 9 and Week 12

• The Model-based Estimated Percentage of Participants Achieving Blood Pressure (BP) Control

  Week 12

Study Arms (5)

Dose 1

EXPERIMENTAL

Lowest dose

Biological: XXB750 drug

Dose 2

EXPERIMENTAL

Dose 2

Biological: XXB750 drug

Dose 3

EXPERIMENTAL

Dose 3

Biological: XXB750 drug

Dose 4

EXPERIMENTAL

Highest dose

Biological: XXB750 drug

Dose 5

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

XXB750 drug BIOLOGICAL

SC injection

Dose 1; Dose 2; Dose 3; Dose 4

Placebo OTHER

SC injection

Dose 5

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants who are ≥ 18 years old.
• Signed informed consent prior to participation in the study.
• Apparent rHTN at screening (Visit 1) defined as uncontrolled BP with an office msSBP ≥ 140 mmHg despite treatment with stable (i.e., unchanged for ≥4 weeks), optimal or maximally tolerated doses of three or four antihypertensive drugs of different classes, including an ACEI/ARB, a long-acting dihydropyridine CCB, and a thiazide or thiazide-like diuretic. Participant with documented intolerance to any doses of CCBs may be eligible if receiving another class of antihypertensive medication at an optimal or maximally tolerated dose (referred to as triple background antihypertensive therapy. An optimal dose is defined as the highest dose taking in to account participant's documented comorbidities and tolerability per investigator's clinical judgment.

You may not qualify if:

• Subjects with the following blood pressures at the specified time points are not eligible to participate in the study:
• Office msSBP \<140 mmHg at Visit 20 OR
• Office msSBP ≥180 mmHg or office msDBP ≥110 mmHg at the end-of-run-in visit (Visit 30) OR
• h mean SBP \>170 mmHg or 24h mean DBP \>105mmHg measured by ABPM at the end of the run-in (Visit 30).
• Known history of secondary hypertension (moderate-to-severe obstructive sleep apnea without receiving CPAP therapy (either face mask or nasal device), renovascular hypertension, primary aldosteronism, pheochromocytoma, Cushing syndrome, aortic coarctation or other cause of secondary hypertension).
• Estimated GFR \<30 mL/min/1.73m2 using CKD-Epi equation at screening (Visit 1) or at end-of-run-in visit (Visit 30).
• Serum potassium \>5.0 mmol/L (or equivalent plasma potassium value) at screening or end-of-run-in visit (Visit 30).
• Current therapy with a mineralocorticoid receptor antagonist (MRA) or sacubitril/valsartan or received an MRA or sacubitril/valsartan within the 4 weeks prior to screening.
• Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma HbA1c ≥9%)
• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), high-grade AV block (e.g., Mobitz type II and third-degree AV block in absence of a pacemaker) within 6 months of screening according to investigator's judgement.
• Chronic non-paroxysmal atrial fibrillation.
• Acute myocardial infarction (AMI) or unstable angina, or any history of ischemic or hemorrhagic stroke within 12 months of screening; or any percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) within 12 months of screening
• History of a renal denervation procedure.
• Mid-arm circumference ≥44 cm. The cuff should snugly fit on the arm with out the margins of cuff overhanging arm musculature.
• Patients with history of hospitalisation for hypertensive emergencies characterised by severe hypertension (usually grade 3) associated with funduscopic changes (flame haemorrhages and/or papilloedema), microangiopathy, disseminated intravascular coagulation, encephalopathy, acute aortic dissection, acute myocardial ischaemia, or acute heart failure any time prior to screening or hospitalisation for non-emergent/non-urgent uncontrolled hypertension without target organ damage within 3 months prior to screening

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (78)

Pinnacle Research Group Llc

Anniston, Alabama, 36207, United States

Location

Parkway Medical Center

Birmingham, Alabama, 35206, United States

Location

Clinical Trials Research Sacramento

Sacramento, California, 95821-2134, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Canvas Clinical Research

Lake Worth, Florida, 33467, United States

Location

Inpatient Research Clinical LLC

Miami Lakes, Florida, 33014, United States

Location

Cardiology Partners Clinical Research Institute

Wellington, Florida, 33449, United States

Location

American Clinical Trials

Acworth, Georgia, 30101, United States

Location

Alliance for Multispecialty Resrch

Wichita, Kansas, 67207, United States

Location

Anderson Medical Research

Ft. Washington, Maryland, 20744, United States

Location

Capitol Cardiology Associates

Lanham, Maryland, 20706, United States

Location

MD Medical Research

Oxon Hill, Maryland, 20745, United States

Location

NexGen Research

Lima, Ohio, 45801, United States

Location

The Research Center of the Upstate

Greenville, South Carolina, 29607, United States

Location

Tennessee Center For Clinical Trials

Tullahoma, Tennessee, 37388, United States

Location

Manassas Clinical Research Center

Manassas, Virginia, 20110, United States

Location

Dominion Medical Associates

Richmond, Virginia, 23219, United States

Location

Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

Location

Novartis Investigative Site

Perth, Western Australia, 6000, Australia

Location

Novartis Investigative Site

Graz, 8036, Austria

Location

Novartis Investigative Site

Vienna, 1190, Austria

Location

Novartis Investigative Site

Pleven, 5800, Bulgaria

Location

Novartis Investigative Site

Sofia, 1202, Bulgaria

Location

Novartis Investigative Site

Sofia, 1233, Bulgaria

Location

Novartis Investigative Site

Sofia, 1709, Bulgaria

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510080, China

Location

Novartis Investigative Site

Baotou, Inner Mongolia, 014010, China

Location

Novartis Investigative Site

Beijing, 101200, China

Location

Novartis Investigative Site

Qingdao, 266000, China

Location

Novartis Investigative Site

Shanghai, 200025, China

Location

Novartis Investigative Site

Brandýs nad Labem, Czech Republic, 250 01, Czechia

Location

Novartis Investigative Site

Prague, 128 08, Czechia

Location

Novartis Investigative Site

Bobigny, 93009, France

Location

Novartis Investigative Site

Lille, 59000, France

Location

Novartis Investigative Site

Paris, 75015, France

Location

Novartis Investigative Site

Tours, 37044, France

Location

Novartis Investigative Site

Elsterwerda, Brandenburg, 04910, Germany

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60594, Germany

Location

Novartis Investigative Site

Berlin, 10787, Germany

Location

Novartis Investigative Site

Erlangen, 91054, Germany

Location

Novartis Investigative Site

Ulm, 89077, Germany

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Brescia, BS, 25123, Italy

Location

Novartis Investigative Site

Milan, MI, 20122, Italy

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Pisa, PI, 56124, Italy

Location

Novartis Investigative Site

Chikushino-shi, Fukuka, 818-8516, Japan

Location

Novartis Investigative Site

Kanazawa, Ishikawa-ken, 920 8650, Japan

Location

Novartis Investigative Site

Yokohama, Kanagawa, 232 0024, Japan

Location

Novartis Investigative Site

Yokosuka, Kanagawa, 239-8567, Japan

Location

Novartis Investigative Site

Kishiwada, Osaka, 596-0042, Japan

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 103-0027, Japan

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104-0031, Japan

Location

Novartis Investigative Site

Chuo-ku, Tokyo, 103-0027, Japan

Location

Novartis Investigative Site

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Novartis Investigative Site

Gdynia, 81-157, Poland

Location

Novartis Investigative Site

Katowice, 40-648, Poland

Location

Novartis Investigative Site

Krakow, 30-002, Poland

Location

Novartis Investigative Site

Wroclaw, 52-416, Poland

Location

Novartis Investigative Site

Bardejov, 085 01, Slovakia

Location

Novartis Investigative Site

Košice, 040 01, Slovakia

Location

Novartis Investigative Site

Nitra, 949 11, Slovakia

Location

Novartis Investigative Site

Svidník, 089 01, Slovakia

Location

Novartis Investigative Site

Seville, Andalusia, 41014, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Terrassa, Catalonia, 08221, Spain

Location

Novartis Investigative Site

Pamplona, Navarre, 31008, Spain

Location

Novartis Investigative Site

Barcelona, 08025, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Valencia, 46010, Spain

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Taipei, 110, Taiwan

Location

Novartis Investigative Site

Taipei, 11217, Taiwan

Location

Novartis Investigative Site

Taoyuan District, 33305, Taiwan

Location

Novartis Investigative Site

London, GBR, EC1M 6BQ, United Kingdom

Location

Novartis Investigative Site

London, W1T 7HA, United Kingdom

Location

Novartis Investigative Site

Salford, M6 8HD, United Kingdom

Location

Related Publications (1)

• White WB, Azizi M, Ferdinand K, Cohen DL, Nuhrenberg T, Lefkowitz M, Jiao R, Rizkala AR, Maboudian M, Williams B. Natriuretic Peptide Receptor-1 Agonist for Resistant Hypertension: A Randomized Phase 2 Trial. J Am Coll Cardiol. 2026 Jan 13:S0735-1097(25)10351-3. doi: 10.1016/j.jacc.2025.11.045. Online ahead of print.

  PMID: 41563174 DERIVED

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants, investigator staff, persons performing the assessments and blinded clinical research associate (CRA) monitoring study conduct remained blinded to the identity of the treatment from the time of randomization until database lock. The study site pharmacist/nurse or other designated qualified site personnel who prepares the study drug and the unblinded clinical research associates (CRA monitoring drug supply and preparation) remained unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The planned duration of treatment is 12 weeks per participant. Participants may be discontinued from treatment earlier due to unacceptable adverse events, disease progression and/or if treatment is discontinued at the discretion of the investigator or the participant. Following the conclusion of the 12-week Randomized Treatment Period, participants will enter an 8-week Safety Follow-up Period in which participants may be treated at the discretion of the investigator taking into account that their blood pressure may still be affected by the study treatment for some time after its discontinuation, especially those who were randomized to XXB750.

Study Record Dates

• First Submitted: September 28, 2022
• First Posted: October 3, 2022
• Study Start: November 8, 2022
• Primary Completion: July 2, 2024
• Study Completion: August 27, 2024
• Last Updated: January 12, 2026
• Results First Posted: October 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

DE (5); SL (4); CN (5); NL (1); FR (4); IT (5); JP (8); AU (2); BU (4); US (18); ES (7); TW (4); CZ (2); PL (4); GB (3)