NCT02939599

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

Terminated Phase 2 Results posted Last updated 5 January 2021

What this trial tests

Phase 2 trial testing QCC374 in Pulmonary Arterial Hypertension in 5 participants. Terminated before completion.

Timeline

1 February 2018

Primary endpoint
6 November 2018

6 November 2018

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	5
Start date	1 February 2018
Primary completion	6 November 2018
Estimated completion	6 November 2018
Sites	4 locations across United Kingdom, United States, Germany

Drugs / interventions tested

• QCC374 — full drug profile →

Conditions studied

• Pulmonary Arterial Hypertension — all drugs for Pulmonary Arterial Hypertension →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Pulmonary Arterial Hypertension. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events (SAEs) in Patients With PAH Over a Two Year Period Primary · Two years

Patients with all (serious and non-serious) adverse events, serious adverse events and death were reported

Participant with AE

Group	Value	95% CI
Arm 1	2
Arm 2	2

Participants with serious AE

Group	Value	95% CI
Arm 1	1
Arm 2	0

Maximum Observed Plasma Concentration (Cmax) Secondary · 16 weeks

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

QCC374: Day 1, Dose Level 0.03 mg

Group	Value	95% CI
QCC374	82	82 – 82

QCC374: Day 112, Dose Level 0.12 mg

Group	Value	95% CI
QCC374	664	664 – 664

Time to Reach the Maximum Plasma Concentration (Tmax) Secondary · 16 Weeks

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.

QCC374: Day 1, Dose Level 0.03 mg

Group	Value	95% CI
QCC374	0.250	0.250 – 0.250

QCC374: Day 112, Dose Level 0.12 mg

Group	Value	95% CI
QCC374	0.0330	0.0330 – 0.0330

Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) Secondary · 16 weeks

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.

QCC374: Day 1, Dose Level 0.03 mg

Group	Value	95% CI
QCC374	118	118 – 118

QCC374: Day 112, Dose Level 0.12 mg

Group	Value	95% CI
QCC374	526	526 – 526

Area Under the Plasma Concentration Time Curve From 0 to the End of a Dosing Interval (AUCtau) Secondary · 16 Weeks

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

QCC374: Day 1, Dose Level 0.03 mg

Group	Value	95% CI
QCC374	134	134 – 134

QCC374: Day 112, Dose Level 0.12 mg

Group	Value	95% CI
QCC374	566	566 – 566

Change From Baseline in Six Minute Walk Distance (6MWD) Secondary · 16 weeks

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.

Group	Value	95% CI
QCC374	452	± 104.65

Change in Tricuspid Annular Peak Systolic Velocity (TA S') at Week 16 (Day 112) Using Echocardiography Secondary · Two Years

Key Right Ventricular (RV) function endpoints such as Tricuspid Annular Peak Systolic Velocity (TA S') were assessed with echocardiography. Only descriptive analysis performed.

Group	Value	95% CI
QCC374	10.90	± NA

Change From Baseline in RV Tei Index at Week 16 (Day 112) Using Echocardiography Secondary · 16 weeks

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.

Group	Value	95% CI
QCC374	0.84	± NA

Change From Baseline in RV Fractional Area Change at Week 16 (Day 112) Using Echocardiography Secondary · 16 weeks

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.

Group	Value	95% CI
QCC374	23.91	± NA

Adverse events — posted to ClinicalTrials.gov

Time frame: through study completion an average of 4.5 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

QCC374 Arm 1

Serious: 1/3 (33%)

Deaths: 0/3

QCC374 Arm 2

Serious: 0/2 (0%)

Deaths: 0/2

Serious adverse events (1 terms)

Reaction	System	QCC374 Arm 1	QCC374 Arm 2
Pulmonary arterial hypertension	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (17 terms — click to expand)

Reaction	System	QCC374 Arm 1	QCC374 Arm 2
Nasopharyngitis	Infections and infestations	—	—
Pain in jaw	Musculoskeletal and connective tissue disorders	—	—
Headache	Nervous system disorders	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Asthenia	General disorders	—	—
Fatigue	General disorders	—	—
Sunburn	Injury, poisoning and procedural complications	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Flushing	Vascular disorders	—	—

Most-reported serious reactions: Pulmonary arterial hypertension.

Data from ClinicalTrials.gov NCT02939599 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Exploring Functional Differences between the Right and Left Ventricles to Better Understand Right Ventricular Dysfunction.
   Bernal-Ramirez J, Díaz-Vesga MC, Talamilla M, Méndez A, et al · · 2021 · cited 20× · PMID 34497685 · DOI 10.1155/2021/9993060