Macitentan in Pulmonary Hypertension of Sickle Cell Disease

NCT02651272 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: H-33165
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study to assess the safety and efficacy of macitentan in patients with pulmonary hypertension of sickle cell disease. This study will enroll approximately 10 subjects. Study participation for each subject will last approximately 24 weeks from screening to end of treatment follow-up.

Conditions

Pulmonary Hypertension; Sickle Cell Disease

Keywords

Pulmonary Hypertension; Sickle Cell Disease; Pulmonary Arterial Hypertension; Macitentan

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events

  The occurrence of treatment emergent AEs includes having any of the following: vaso-occlusive crises requiring hospitalization; acute congestive heart failure; hypotension (defined as a mean arterial pressure less than 60mmHg); decrease in hemoglobin concentration by greater than 1 g/dL.

  20 weeks

Secondary Outcomes (11)

• Change in Right Arterial Pressure (RAP)

  Baseline, 16 weeks

• Change in Systolic Right Ventricular Pressure (RVSP)

  Baseline, 16 weeks

• Change in Diastolic Pulmonary Artery Pressure (PADP)

  Baseline, 16 weeks

• Change in Systolic Pulmonary Artery Pressure (SPAP)

  Baseline, 16 weeks

• Change in Systemic Vascular Resistance Index (SVR)

  Baseline, Week 16

Study Arms (1)

macitentan

EXPERIMENTAL

10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks.

Drug: macitentan

Interventions

macitentan DRUG

10mg macitentan tablets

Also known as: opsumit

macitentan

Eligibility Criteria

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

You may qualify if:

• A diagnosis of sickle cell disease (HbSS, HbSC, HbS- β+ or 0) confirmed by hemoglobin electrophoresis
• Provision of informed consent
• Suspicion of Pulmonary Hypertension by echocardiography within the last 6 months (RVSP \> 40mmHg or a TRV \> 3.0 m/sec) or diagnosis of Pulmonary Hypertension by cardiac catheterization within the last 12 months (mean Pulmonary Artery Pressure \[PAP\] ≥25 mmHg at rest). Left ventricular ejection fraction \> 50%.
• Right heart catheterization which demonstrates the following:
• mean pulmonary arterial pressure \[mPAP\] \> 25 mmHg
• pulmonary artery occluded pressure \[PAOP\] or LVEDP \< 15 mmHg
• PVR \> 160 dynes-sec/cm5 or 2 Wood Units
• Age \> 18 years
• NYHA Class II or III by symptoms
• Six minute walk distance (6MWD) \> 150 meters and \< 450 meters
• A woman of child-bearing potential is eligible only if the following applies:
• Negative pre-treatment serum pregnancy test and agreement to monthly tests
• Use of two highly effective methods of contraception if not truly abstinent with a male partner OR permanent female sterilization has been performed.
• May be on background therapy or may be treatment naïve.

You may not qualify if:

• Current pregnancy or lactation
• Any one of the following medical conditions:
• Stroke within the last 6 weeks
• New diagnosis of pulmonary embolism within the last 3 months
• Clinically significant laboratory abnormalities, including, but not limited to: Positive Hepatitis B surface antigen or Hepatitis C antibody, Positive HIV test, Serum alanine aminotransferase (ALT) greater than or equal to 2.0 x ULN, Serum creatinine greater than or equal to 2.5mg/dL (or calculated creatinine clearance less than or equal to 30mL/min).
• Hospitalization within the prior 4 weeks for a vasoocclusive crisis or acute chest syndrome
• Any unstable (acute or chronic) condition that in the opinion of the investigator will prevent completion of the study
• Evidence of diastolic dysfunction of the left ventricle as defined by a mPAP \> 25 mmHg and PCWP or LVEDP \> 15 mmHg by right heart catheterization with a normal left ventricular ejection fraction by echocardiogram or MUGA.
• Left ventricular ejection fraction \< 50% of significant ischemic, valvular or constrictive heart disease
• Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements (particularly the 6MWT) e.g. symptomatic hip osteonecrosis
• Active therapy with an IV prostacyclin
• Subjects who are taking other investigational medications at the time of the study
• Clinically significant psychiatric, addictive (defined by DSM-IV criteria), neurologic disease or condition that, in the opinion of the Investigator, would compromise his/her ability to give informed consent, participate fully in this study, or prevent adherence to the requirements of the study protocol.

Sponsors & Collaborators

• Boston University: lead
• Actelion: collaborator

Study Sites (1)

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Related Publications (6)

• Mehari A, Gladwin MT, Tian X, Machado RF, Kato GJ. Mortality in adults with sickle cell disease and pulmonary hypertension. JAMA. 2012 Mar 28;307(12):1254-6. doi: 10.1001/jama.2012.358. No abstract available.

  PMID: 22453563 BACKGROUND

• Parent F, Bachir D, Inamo J, Lionnet F, Driss F, Loko G, Habibi A, Bennani S, Savale L, Adnot S, Maitre B, Yaici A, Hajji L, O'Callaghan DS, Clerson P, Girot R, Galacteros F, Simonneau G. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med. 2011 Jul 7;365(1):44-53. doi: 10.1056/NEJMoa1005565.

  PMID: 21732836 BACKGROUND

• Fonseca GH, Souza R, Salemi VM, Jardim CV, Gualandro SF. Pulmonary hypertension diagnosed by right heart catheterisation in sickle cell disease. Eur Respir J. 2012 Jan;39(1):112-8. doi: 10.1183/09031936.00134410. Epub 2011 Jul 20.

  PMID: 21778170 BACKGROUND

• Klings ES, Machado RF, Barst RJ, Morris CR, Mubarak KK, Gordeuk VR, Kato GJ, Ataga KI, Gibbs JS, Castro O, Rosenzweig EB, Sood N, Hsu L, Wilson KC, Telen MJ, Decastro LM, Krishnamurti L, Steinberg MH, Badesch DB, Gladwin MT; American Thoracic Society Ad Hoc Committee on Pulmonary Hypertension of Sickle Cell Disease. An official American Thoracic Society clinical practice guideline: diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease. Am J Respir Crit Care Med. 2014 Mar 15;189(6):727-40. doi: 10.1164/rccm.201401-0065ST.

  PMID: 24628312 BACKGROUND

• Barst RJ, Mubarak KK, Machado RF, Ataga KI, Benza RL, Castro O, Naeije R, Sood N, Swerdlow PS, Hildesheim M, Gladwin MT; ASSET study group*. Exercise capacity and haemodynamics in patients with sickle cell disease with pulmonary hypertension treated with bosentan: results of the ASSET studies. Br J Haematol. 2010 May;149(3):426-35. doi: 10.1111/j.1365-2141.2010.08097.x. Epub 2010 Feb 17.

  PMID: 20175775 BACKGROUND

• Machado RF, Barst RJ, Yovetich NA, Hassell KL, Kato GJ, Gordeuk VR, Gibbs JS, Little JA, Schraufnagel DE, Krishnamurti L, Girgis RE, Morris CR, Rosenzweig EB, Badesch DB, Lanzkron S, Onyekwere O, Castro OL, Sachdev V, Waclawiw MA, Woolson R, Goldsmith JC, Gladwin MT; walk-PHaSST Investigators and Patients. Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity. Blood. 2011 Jul 28;118(4):855-64. doi: 10.1182/blood-2010-09-306167. Epub 2011 Apr 28.

  PMID: 21527519 BACKGROUND

MeSH Terms

Conditions

Hypertension, Pulmonary; Anemia, Sickle Cell; Pulmonary Arterial Hypertension

Interventions

macitentan

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

Early termination as unable to enroll participants.

Results Point of Contact

• Title: Elizabeth Klings, MD
• Organization: Bosotn Medical Center

elizabeth.klings@bmc.org

617-638-7480

Study Officials

• Elizabeth Klings, MD

  Boston University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Study is Open Label
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: January 8, 2016
• Study Start: July 1, 2015
• Primary Completion: December 18, 2019
• Study Completion: December 18, 2019
• Last Updated: December 8, 2020
• Results First Posted: December 8, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)