Safety, pharmacokinetics and efficacy study of QCC374 in PAH patients

• Register: EUCTR
• Last refreshed on: 20 July 2020
• Main ID: EUCTR2016-001412-38-DE
• Date of registration: 03/04/2017
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma AG
• 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: 27/07/2017
• Target sample size: 38
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001412-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

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.
Other protocol-defined inclusion criteria may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

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 or subjects with PAH responsive to high dose calcium channel blockers.
• 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 left sided heart disease, chronic left sided heart failure, congenital or acquired valvular disease and/or pulmonary venous hypertension, as determined by history or echocardiogram at baseline visit.
• Subjects with obstructive (FEV1/ FVC < 70% predicted and FEV1 < 70% predicted) or restrictive (total lung capacity < 65% predicted and/or clinically significant abnormality on CXR) lung disease at screening.

Other protocol-defined exclusion criterias may apply.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Pulmonary arterial hypertension
MedDRA version: 20.0 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Code: QCC374 0.015 mg
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: TBD
Current Sponsor code: QCC374
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.015-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Product Code: QCC374 0.06 mg
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: TBD
Current Sponsor code: QCC374
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.06-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 16 weeks

Primary end point(s): Percentage of the baseline PVR at week 16

Main Objective: To assess the efficacy of 16 weeks of QCC374 administration in adult patients with PAH

Secondary Objective: • To evaluate the safety and tolerability of multiple doses of QCC374 in patients with PAH
• To evaluate the preliminary efficacy of 16 weeks of QCC374 administration in patients with PAH by measuring changes from baseline in:
- Six minute walk distance (6MWD)
- Hemodynamic parameters other than PVR
- Right ventricular (RV) function with echocardiography
• To evaluate the pharmacokinetics of QCC374 and its metabolite QCM441 in patients with PAH

Secondary Outcome(s)

Secondary end point(s): • AEs, SAEs and all safety assessments
• 6MWD
• mPAP, PCWP, CO, SVR
• Key RV function endpoints with echocardiography including but not limited to tricuspid annular peak systolic velocity (TA S'), RV Tei index and RV fractional area change.
• PK parameters of primary interest (Cmax Tmax, AUClast, AUCtau) of QCC374 and QCM441 in plasma.

Timepoint(s) of evaluation of this end point: 16 weeks

Secondary ID(s)

CQCC374X2201

NCT02927366

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date: 09/03/2017
Contact:

Results

• Results available: Yes
• Date Posted: 19/06/2019
• Date Completed: 11/07/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001412-38/results