Selexipag for the Treatment of Schistosomiasis-Associated Pulmonary Arterial Hypertension (SELSCH)

Pulmonary arterial hypertension (PAH) is a severe, progressive and potentially fatal disease that impairs the pulmonary circulation and leads to right ventricular failure. One of the world most prevalent etiologies of PAH is schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH). New drugs have emerged to treat other forms of PAH, but their benefits cannot be automatically translated for Sch-PAH patients, since this etiology was not included in the pivotal PAH trials. One of the most promising therapies for the treatment of PAH to emerge in recent years is selexipag, an oral IP receptor agonist, which acts on the prostacyclin pathway. The present study aims to evaluate the efficacy, safety and tolerability of selexipague for the treatment of schistosomiasis-associated pulmonary arterial hypertension.

Study Overview

• Status: Unknown
• Conditions: Pulmonary Hypertension; Schistosomiasis
• Intervention / Treatment: Drug: Selexipag

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • SP
    • São Paulo, SP, Brazil, 05048000
      • Recruiting
      • Universidade de São Paulo
      • Contact: Caio Fernandes, PhD; Phone Number: 011-992149574; Email: cjcfernandes@yahoo.com.br

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with symptomatic Sch-PAH. Sch-PAH diagnosis necessarily include the three criteria below

  1. Invasive confirmation of PAH, according to the criteria defined in the Pulmonary Hypertension Sixth World Symposium: mean pulmonary artery pressure higher than 20 mmHg, at rest, and the presence of pulmonary vascular resistance (PVR) equal to or greater than 3 W, and a pulmonary capillary pressure considered normal (equal to or lower than 15 mmHg (1)).
  2. At least one epidemiological criteria for chronic schistosomiasis: patient from a highly prevalent region for schistosomiasis or previous history of parasitic treatment for schistosomiasis or the presence of Schistosoma mansoni eggs in the patient's feces

  3. Evidence of long-term hepatosplenic involvement by schistosomiasis, via compatible ultrasound findings (peri-portal fibrosis or enlarged left lobe) All patients will necessarily already be receiving at least one specific treatment for PAH, either with phosphodiesterase V inhibitor or with an endothelin receptor antagonist, with a stable dose for at least 12 weeks before inclusion in the study.

     Exclusion Criteria:

• Patient without clinical condition to perform the 6-minute walk test
• Patient with gastro-intestinal bleeding for over 12 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Selexipag; Selexipag will be up titrated for a period that will last 12 weeks (Phase 2). The initial dose will be 200 mcg of selexipag every 12 hours, with weekly dose increases of 200 mcg, up to the maximum dose of 1600 mcg every 12 hours or until the classic side effects of the prostacyclin pathway drugs (headache, mandibular pain), among others) arise. The dose will then be reduced by 200 mcg per dose, and this will be the maximum dose considered for that particular patient, maintained in Phase 3 (16 weeks).

Drug: Selexipag; treatment with selexipag

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pulmonary vascular resistance	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FC	New York Heart Association Functional Class	16 weeks
6MWT	Lenght in the six minute walking distance test	16 weeks
BNP	Brain Natriuretic Peptide	16 weeks
HSP 70	Heat shock protein 70	16 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ESC/ERS risk stratification category	ESC/ERS risk stratification category	16 weeks

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: Janssen-Cilag Ltd.
• Investigators: Principal Investigator: Caio J Fernandes, PHD, USP

Study record dates

Study Major Dates

• Study Start (Anticipated): October 15, 2020
• Primary Completion (Anticipated): November 30, 2021
• Study Completion (Anticipated): March 31, 2022

Study Registration Dates

• First Submitted: October 8, 2020
• First Submitted That Met QC Criteria: October 8, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 8, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: treatment; safety; efficacy; schistosomiasis; pulmonary arterial hypertension; selexipag
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Infections; Respiratory Tract Diseases; Lung Diseases; Vector Borne Diseases; Parasitic Diseases; Helminthiasis; Trematode Infections; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Schistosomiasis; Antihypertensive Agents; Selexipag
• Other Study ID Numbers: UAP129

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No