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

A Multi-center, Randomized, Double-blind, Parallel-group, 20-week Dose-finding Study to Evaluate Efficacy, Safety, and Tolerability of XXB750 in Patients With Resistant Hypertension

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).

Study Overview

• Status: Completed
• Conditions: Resistant Hypertension
• Intervention / Treatment: Other: Placebo; Biological: XXB750 drug

Detailed Description

Subjects will enter run-in period which lasts for approximately 2 weeks. The study duration is for 20 weeks during which each participant will receive a total of 3 doses of study medication (in addition to 1 dose of study medication during run-in). Participants will be followed to monitor their safety for an additional 8 weeks during which time no active study medication will be given.

• Study Type: Interventional
• Enrollment (Actual): 189
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Novartis Investigative Site
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Novartis Investigative Site
• Austria
  • Graz, Austria, 8036
    • Novartis Investigative Site
  • Vienna, Austria, 1190
    • Novartis Investigative Site
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1202
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1233
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1709
    • Novartis Investigative Site
• China
  • Beijing, China, 101200
    • Novartis Investigative Site
  • Qingdao, China, 266000
    • Novartis Investigative Site
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Novartis Investigative Site
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 014010
      • Novartis Investigative Site
• Czechia
  • Prague, Czechia, 128 08
    • Novartis Investigative Site
  • Czech Republic
    • Brandýs nad Labem, Czech Republic, Czechia, 250 01
      • Novartis Investigative Site
• France
  • Bobigny, France, 93009
    • Novartis Investigative Site
  • Lille, France, 59000
    • Novartis Investigative Site
  • Paris, France, 75015
    • Novartis Investigative Site
  • Tours, France, 37044
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10787
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Ulm, Germany, 89077
    • Novartis Investigative Site
  • Brandenburg
    • Elsterwerda, Brandenburg, Germany, 04910
      • Novartis Investigative Site
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60594
      • Novartis Investigative Site
• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • BS
    • Brescia, BS, Italy, 25123
      • Novartis Investigative Site
  • MI
    • Milan, MI, Italy, 20162
      • Novartis Investigative Site
    • Milan, MI, Italy, 20122
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56124
      • Novartis Investigative Site
• Japan
  • Fukuka
    • Chikushino-shi, Fukuka, Japan, 818-8516
      • Novartis Investigative Site
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920 8650
      • Novartis Investigative Site
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 232 0024
      • Novartis Investigative Site
    • Yokosuka, Kanagawa, Japan, 239-8567
      • Novartis Investigative Site
  • Osaka
    • Kishiwada, Osaka, Japan, 596-0042
      • Novartis Investigative Site
  • Tokyo
    • Chuo Ku, Tokyo, Japan, 103-0027
      • Novartis Investigative Site
    • Chuo Ku, Tokyo, Japan, 104-0031
      • Novartis Investigative Site
    • Chuo-ku, Tokyo, Japan, 103-0027
      • Novartis Investigative Site
• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105 AZ
      • Novartis Investigative Site
• Poland
  • Gdynia, Poland, 81-157
    • Novartis Investigative Site
  • Katowice, Poland, 40-648
    • Novartis Investigative Site
  • Krakow, Poland, 30-002
    • Novartis Investigative Site
  • Wroclaw, Poland, 52-416
    • Novartis Investigative Site
• Slovakia
  • Bardejov, Slovakia, 085 01
    • Novartis Investigative Site
  • Košice, Slovakia, 040 01
    • Novartis Investigative Site
  • Nitra, Slovakia, 949 11
    • Novartis Investigative Site
  • Svidník, Slovakia, 089 01
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08025
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Valencia, Spain, 46010
    • Novartis Investigative Site
  • Andalusia
    • Seville, Andalusia, Spain, 41014
      • Novartis Investigative Site
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Novartis Investigative Site
    • Terrassa, Catalonia, Spain, 08221
      • Novartis Investigative Site
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 11217
    • Novartis Investigative Site
  • Taipei, Taiwan, 110
    • Novartis Investigative Site
  • Taoyuan District, Taiwan, 33305
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, W1T 7HA
    • Novartis Investigative Site
  • Salford, United Kingdom, M6 8HD
    • Novartis Investigative Site
  • GBR
    • London, GBR, United Kingdom, EC1M 6BQ
      • Novartis Investigative Site
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group Llc
    • Birmingham, Alabama, United States, 35206
      • Parkway Medical Center
  • California
    • Sacramento, California, United States, 95821-2134
      • Clinical Trials Research Sacramento
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Lake Worth, Florida, United States, 33467
      • Canvas Clinical Research
    • Miami Lakes, Florida, United States, 33014
      • Inpatient Research Clinical LLC
    • Wellington, Florida, United States, 33449
      • Cardiology Partners Clinical Research Institute
  • Georgia
    • Acworth, Georgia, United States, 30101
      • American Clinical Trials
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Alliance for Multispecialty Resrch
  • Maryland
    • Ft. Washington, Maryland, United States, 20744
      • Anderson Medical Research
    • Lanham, Maryland, United States, 20706
      • Capitol Cardiology Associates
    • Oxon Hill, Maryland, United States, 20745
      • MD Medical Research
  • Ohio
    • Lima, Ohio, United States, 45801
      • Nexgen Research
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • The Research Center of The Upstate
  • Tennessee
    • Tullahoma, Tennessee, United States, 37388
      • Tennessee Center for Clinical Trials
  • Virginia
    • Manassas, Virginia, United States, 20110
      • Manassas Clinical Research Center
    • Richmond, Virginia, United States, 23219
      • Dominion Medical Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and female participants who are ≥ 18 years old.
2. Signed informed consent prior to participation in the study.
3. 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.
4. Mean 24hr SBP ≥135 mmHg (measured by ABPM) at the end-of Run-in-Visit (Visit 30) on treatment with optimal or maximally tolerated doses of an ACEI/ARB, a long-acting dihydropyridine CCB (or a suitable alternative in case of intolerance per inclusion criterion above), and a thiazide or thiazide-like diuretic.

Exclusion Criteria:

1. Subjects with the following blood pressures at the specified time points are not eligible to participate in the study:

   1. Office msSBP <140 mmHg at Visit 20 OR
   2. Office msSBP ≥180 mmHg or office msDBP ≥110 mmHg at the end-of-run-in visit (Visit 30) OR
   3. 24h mean SBP >170 mmHg or 24h mean DBP >105mmHg measured by ABPM at the end of the run-in (Visit 30).
2. 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).
3. Estimated GFR <30 mL/min/1.73m2 using CKD-Epi equation at screening (Visit 1) or at end-of-run-in visit (Visit 30).
4. Serum potassium >5.0 mmol/L (or equivalent plasma potassium value) at screening or end-of-run-in visit (Visit 30).
5. 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.
6. Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma HbA1c ≥9%)
7. 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.
8. Chronic non-paroxysmal atrial fibrillation.
9. 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
10. History of a renal denervation procedure.
11. Mid-arm circumference ≥44 cm. The cuff should snugly fit on the arm with out the margins of cuff overhanging arm musculature.
12. 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
13. Receiving more than 4 antihypertensive medications.
14. Night shift workers.
15. History of presence of any other disease where the life expectancy is less than 3 years.
16. History of malignancy of any organ system (other than localized basal or squamous cell carcinoma of the skin or localized prostate cancer), treated or untreated, within the past 3 years, regardless of whether there is evidence of local recurrence or metastases.
17. Evidence of hepatic disease as determined by any one of the following: SGOT (AST) or SGPT (ALT) values exceeding 3x the upper limit of normal (ULN), or bilirubin >1.5 mg/dl at Visit 1.
18. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
19. History of drug abuse or alcohol dependency.
20. Lacking the ability to comprehend or follow instructions, or for any reason in the opinion of the investigator, a participant that would be unlikely or unable to comply with study protocol.
21. Concurrent enrollment in any other investigational drug or device trial (participation in non-interventional registries is acceptable).
22. Requiring prolonged/regular use of NSAIDs except for prophylactic use of low dose aspirin up to 325 mg QD or other prohibited medications during of the study (i.e., required use for longer than 1 week).

23. Pregnant, nursing or planning to become pregnant (documented negative pregnancy test required within a maximum of 7 days prior to enrollment of all women of childbearing potential). Documentation of highly effective contraception is also required for women of childbearing potential (see below).

    Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 3 months after stopping medication. Highly effective contraception methods include:

    • Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptom-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
    • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
    • Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant.
    • Use of oral, (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.

    In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

    Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate history of vasomotor symptoms). Women are considered not of childbearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of child bearing potential.

    If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF.

24. History of hypersensitivity to any of the study drugs, excipients or drugs of similar class.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose 2	Biological: XXB750 drug; SC injection
Experimental: Dose 3	Biological: XXB750 drug; SC injection
Experimental: Dose 1; Lowest dose	Biological: XXB750 drug; SC injection
Experimental: Dose 4; Highest dose	Biological: XXB750 drug; SC injection
Placebo Comparator: Dose 5; Placebo	Other: Placebo; SC injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in SBP 24 Hours at Week 12 (Difference Between Highest XXB750 Dose and Placebo)	To evaluate the treatment effect of the highest XXB750 dose versus placebo in reducing the mean 24 hours SBP from baseline to Week 12. Automated arterial BP determinations and pulse rate readings were made with Microlife Watch BP Office 2G, an automated digital BP device.	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)	To evaluate the treatment effect of the highest XXB750 dose versus placebo in the dosing interval average of ambulatory SBP as assessed by average of mean 24 hours SBP measured at week 9 and week 12. Automated arterial BP determinations and pulse rate readings were made with Microlife Watch BP Office 2G, an automated digital BP device.	Baseline, Week 9 and Week 12
The Model-based Estimated Percentage of Participants Achieving Blood Pressure (BP) Control	To evaluate the percentage of participants achieving ambulatory BP control defined as mean 24 hours SBP <130 mmHg and mean 24 hours DBP < 80 mmHg with respect to the dose-response relationship of the four XXB750 dose level groups compared to placebo at week 12. Automated arterial BP determinations and pulse rate readings were made with Microlife Watch BP Office 2G, an automated digital BP device. Percentage of participants is derived from dose response analysis, using generalized MCP-Mod methodology for binary data.	Week 12

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2022
• Primary Completion (Actual): July 2, 2024
• Study Completion (Actual): August 27, 2024

Study Registration Dates

• First Submitted: September 28, 2022
• First Submitted That Met QC Criteria: September 28, 2022
• First Posted (Actual): October 3, 2022

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: hypertension; resistant hypertension; rHTN; not controlled hypertension
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension
• Other Study ID Numbers: CXXB750B12201; 2021-005738-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

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