Safety, Pharmacokinetics and Efficacy Study of QCC374 in PAH Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02927366
• Date of registration: 05/10/2016
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Safety, Pharmacokinetics and Efficacy Study of QCC374 in PAH Patients
• Scientific title: A Randomized, Parallel-group, Placebo-controlled Subject and Investigator Blinded Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of QCC374 in the Treatment of Pulmonary Arterial Hypertension
• Date of first enrolment: September 19, 2017
• Target sample size: 8
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02927366
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Germany, Korea, Republic of, Taiwan, United Kingdom, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male and female patients 18 years of age or older with symptomatic PAH.

- Subjects with PAH belonging to one of the following subgroups of the Updated Clinical
Classification Group 1 (Nice, 2013):

- Idiopathic PAH

- familial PAH

- PAH associated with connective tissue disease, congenital heart disease (surgically
repaired at least 12 months prior to screening) or drug or toxin induced (for example,
anorexigen use).

- Subjects must have persistent symptoms due to PAH despite therapy with at least one of
the following PAH medications: an endothelin receptor antagonist, asoluble guanylate
cyclase stimulator or a phosphodiesterase inhibitor. The subjects' PAH medication
regimen, with typical medications including calcium channel blockers, endothelin
receptor antagonists, soluble guanylate cyclase stimulators and/or phosphodiesterase
inhibitors, must have been used at a stable dose and frequency for at least 12 weeks
before the screening visit and during the screening period.

- Diagnosis of PAH established according to the standard criteria before the screening
visit:

- Resting mean pulmonary arterial pressure > 25 mmHg.

- PVR > 240 dynes s/cm5.

- Pulmonary capillary wedge pressure or left ventricular end diastolic pressure < 15
mmHg

- PVR > 400 dynes s/cm5 at the time of the baseline right heart catheterization (RHC)
(if a RHC was completed within one month of the screening visit, that result may be
used for inclusion).

- 6-minute walk distance greater than 150 meters at Screening. This distance must be
confirmed by a second 6MWT prior to randomization. The value of the second 6MWD should
be within ± 15% of the value obtained at Screening.

Exclusion Criteria:

- Subjects with clinically unstable right heart failure within the last three months
(New York Heart Association (NYHA) Class IV).

- Subjects with PAH associated with portal hypertension, Human Immunodeficiency Virus
(HIV) infection or unrepaired congenital systemic to pulmonary shunts

- Subjects who have received or have been scheduled to receive long-term treatment with
epoprostenol or any prostacyclin within the three months prior to the screening visit
or during the screening period.

- Hypotensive subjects (systemic systolic blood pressure < 85 mmHg)

- Subjects with a history of left sided heart disease, chronic left sided heart failure,
congenital or acquired valvular disease and/or pulmonary venous hypertension.

- Subjects with significant obstructive (forced expiratory volume in one second
[FEV1]/forced vital capacity [FVC] < 70% predicted) or restrictive (total lung
capacity < 70% predicted) lung disease at screening.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: QCC374

Drug: Placebo Matching

Primary Outcome(s)

Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 16 (Day 111) [Time Frame: Baseline, Week 16 (Day 111)]

Secondary Outcome(s)

Change From Baseline in Systemic Vascular Resistance (SVR) at Week 16 (Day 111) [Time Frame: Baseline, Week 16 (Day 111)]

Area Under the Plasma Concentration Time Curve From 0 to the End of a Dosing Interval (AUCtau) for QCC374 and Its Metabolite QCM441 [Time Frame: Day 1 and 112 (0.00, 0.05, 0.15, 0.30, 1.00, 2.00, 4.00, 8.00 and 12.00 hours post-dose))]

Change From Baseline in Six Minute Walk Distance (6MWD) Over Time [Time Frame: Baseline, Day 28, Day 56, Day 84 and Day 111]

Maximum Observed Plasma Concentration (Cmax) for QCC374 and Its Metabolite QCM441 [Time Frame: Day 1 and 112 (0.00, 0.05, 0.15, 0.30, 1.00, 2.00, 4.00, 8.00 and 12.00 hours post-dose))]

Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Week 16 (Day 111) [Time Frame: Baseline, Week 16 (Day 111)]

Change From Baseline in RV Fractional Area Change and RV Free Wall Average Peak Long Strain at Week 16 (Day 111) Using Echocardiography [Time Frame: Baseline, Week 16 (Day 111)]

Change From Baseline in RV Tei Index at Week 16 (Day 111) Using Echocardiography [Time Frame: Baseline, Week 16 (Day 111)]

Change From Baseline in Tricuspid Annular Peak Systolic Velocity (TA S') at Week 16 (Day 111) Using Echocardiography [Time Frame: Baseline, Week 16 (Day 111)]

Change From Baseline in Cardiac Index at Week 16 (Day 111) [Time Frame: Baseline, Week 16 (Day 111)]

Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) for QCC374 and Its Metabolite QCM441 [Time Frame: Day 1 and 112 (0.00, 0.05, 0.15, 0.30, 1.00, 2.00, 4.00, 8.00 and 12.00 hours post-dose))]

Change From Baseline in Tricuspid Annular Plane Sys Excursion (TAPSE) at Week 16 (Day 111) Using Echocardiography [Time Frame: Baseline, Week 16 (Day 111)]

Change From Baseline in Cardiac Output (CO) at Week 16 (Day 111) [Time Frame: Baseline, Week 16 (Day 111)]

Time to Reach the Maximum Plasma Concentration (Tmax) for QCC374 and Its Metabolite QCM441 [Time Frame: Day 1 and 112 (0.00, 0.05, 0.15, 0.30, 1.00, 2.00, 4.00, 8.00 and 12.00 hours post-dose))]

Secondary ID(s)

CQCC374X2201

2016-001412-38

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 07/08/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02927366