Long-term Extension Study of the Safety and Pharmacokinetics of QCC374 in PAH Patients

Long-term, Open Label, Multicenter, Extension Study to Evaluate the Safety and Tolerability of QCC374 in Patients With Pulmonary Arterial Hypertension (PAH)

This is a long-term open-label safety extension to the Phase 2a study of inhaled QCC374 in adult patients with PAH. This study provides the patients who completed the QCC374X2201 study with the option to continue receiving QCC374. The study will monitor the long-term safety, tolerability and efficacy of QCC374 in patients with PAH.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: QCC374

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
      • Novartis Investigative Site
• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15261
      • Novartis Investigative Site

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:

• Written informed consent must be obtained before any assessment is performed.
• Subject was enrolled in the QCC374X2201 study and completed per protocol

Exclusion Criteria:

• Subjects who have started receiving prostacyclin (epoprostenol), prostacyclin analogs (i.e. trepostinil, iloprost, beraprost) or prostacyclin receptor agonists (i.e. selexipag) since the last study drug intake in the QCC374X2201 study.
• Females who are pregnant, or who plan to become pregnant during the study, or who are breastfeeding
• Any known factor or disease that may interfere with treatment compliance or study conduct (i.e. drug or alcohol dependence)
• Subjects who withdrew consent from the study QCC374X2201

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
Experimental: QCC374; placebo patients from QCC374X2201 rolled into extension study will start at 0.03mg b.i.d. or 0.06mg b.i.d. and have the opportunity to up-titrate 0.12mg -active patients will continue at the dose they finished on the QCC374X2201 study	Drug: QCC374; 0.015mg and 0.06mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events (SAEs) in Patients With PAH Over a Two Year Period	Patients with all (serious and non-serious) adverse events, serious adverse events and death were reported	Two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax)	Cmax is the maximum (peak) observed plasma drug concentration after single dose administration. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed	16 weeks
Time to Reach the Maximum Plasma Concentration (Tmax)	Tmax is the time to reach maximum plasma concentration after single dose administration. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.	16 Weeks
Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast)	AUClast is the area under the plasma concentration-time curve from time zero to the last measurable concentration sampling time. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.	16 weeks
Area Under the Plasma Concentration Time Curve From 0 to the End of a Dosing Interval (AUCtau)	AUCtau is the area under the plasma concentration-time curve from time zero to the end of the dosing interval. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed	16 Weeks
Change From Baseline in Six Minute Walk Distance (6MWD)	The Six Minute Walk Test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway. Only descriptive analysis performed.	16 weeks
Change in Tricuspid Annular Peak Systolic Velocity (TA S') at Week 16 (Day 112) Using Echocardiography	Key Right Ventricular (RV) function endpoints such as Tricuspid Annular Peak Systolic Velocity (TA S') were assessed with echocardiography. Only descriptive analysis performed.	Two Years
Change From Baseline in RV Tei Index at Week 16 (Day 112) Using Echocardiography	Key Right Ventricular (RV) function endpoints such as Tei Index were assessed with echocardiography. The RV Tei index is using both systolic and diastolic time intervals to evaluate the overall global dysfunction of the right ventricle in PAH patients. A lower number in RV Tei Index indicates an improvement. Only descriptive analysis performed.	16 weeks
Change From Baseline in RV Fractional Area Change at Week 16 (Day 112) Using Echocardiography	Key Right Ventricular (RV) function endpoints such as Tei Index were assessed with echocardiography. The RV Tei index is using both systolic and diastolic time intervals to evaluate the overall global dysfunction of the right ventricle in PAH patients. A lower number in RV Tei Index indicates an improvement. Only descriptive analysis performed.	16 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2018
• Primary Completion (Actual): November 6, 2018
• Study Completion (Actual): November 6, 2018

Study Registration Dates

• First Submitted: October 12, 2016
• First Submitted That Met QC Criteria: October 18, 2016
• First Posted (Estimate): October 20, 2016

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Cough; Dizziness; Shortness of breath; Fainting; Pulmonary hypertension (PH),; Increase blood pressure in the pulmonary artery; Increased blood pressure in the pulmonary vein; Increased blood pressure in the lung vasculature; Leg swelling; Angina pector
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: CQCC374X2201E1

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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