Trial Outcomes & Findings for Long-term Extension Study of the Safety and Pharmacokinetics of QCC374 in PAH Patients (NCT NCT02939599)

NCT ID: NCT02939599

Last Updated: 2021-01-05

Results Overview

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

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

Two years

Results posted on

2021-01-05

Participant Flow

Participant milestones

Participant milestones
Measure	Arm 1 Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study	Arm 2 Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol
Overall Study STARTED	3	2
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1 Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study	Arm 2 Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol
Overall Study Adverse Event	1	0
Overall Study Study Terminated By Sponsor	2	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1 n=3 Participants Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study 0.12mg -active patients will continue at the dose they finished on the QCC374X2201 study	Arm2 n=2 Participants Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol	Total n=5 Participants Total of all reporting groups
Age, Continuous	40.3 Years STANDARD_DEVIATION 4.93 • n=5 Participants	58.0 Years STANDARD_DEVIATION 9.90 • n=7 Participants	47.4 Years STANDARD_DEVIATION 11.41 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Two years

Population: Safety set includes all participants who received at least one dose of study drug

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

Outcome measures

Outcome measures
Measure	Arm 1 n=3 Participants Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study 0.12mg -active patients will continue at the dose they finished on the QCC374X2201 study	Arm 2 n=2 Participants Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol
Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events (SAEs) in Patients With PAH Over a Two Year Period Participant with AE	2 Participants	2 Participants
Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events (SAEs) in Patients With PAH Over a Two Year Period Participants with serious AE	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 16 weeks

Population: Participants from the Pharmacokinetic (PK) analysis set, defined as all randomized participants who received at least one dose of study drug and one evaluable PK concentration measurement, with data available for analysis were considered

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

Outcome measures

Outcome measures
Measure	Arm 1 n=1 Participants Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study 0.12mg -active patients will continue at the dose they finished on the QCC374X2201 study	Arm 2 Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol
Maximum Observed Plasma Concentration (Cmax) QCC374: Day 1, Dose Level 0.03 mg	82 pg/mL Interval 82.0 to 82.0	—
Maximum Observed Plasma Concentration (Cmax) QCC374: Day 112, Dose Level 0.12 mg	664 pg/mL Interval 664.0 to 664.0	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm 1 n=1 Participants Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study 0.12mg -active patients will continue at the dose they finished on the QCC374X2201 study	Arm 2 Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol
Time to Reach the Maximum Plasma Concentration (Tmax) QCC374: Day 1, Dose Level 0.03 mg	0.250 hour Interval 0.25 to 0.25	—
Time to Reach the Maximum Plasma Concentration (Tmax) QCC374: Day 112, Dose Level 0.12 mg	0.0330 hour Interval 0.033 to 0.033	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm 1 n=1 Participants Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study 0.12mg -active patients will continue at the dose they finished on the QCC374X2201 study	Arm 2 Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol
Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) QCC374: Day 1, Dose Level 0.03 mg	118 h*pg/mL Interval 118.0 to 118.0	—
Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) QCC374: Day 112, Dose Level 0.12 mg	526 h*pg/mL Interval 526.0 to 526.0	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Arm 1 n=1 Participants Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study 0.12mg -active patients will continue at the dose they finished on the QCC374X2201 study	Arm 2 Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol
Area Under the Plasma Concentration Time Curve From 0 to the End of a Dosing Interval (AUCtau) QCC374: Day 1, Dose Level 0.03 mg	134 h*pg/mL Interval 134.0 to 134.0	—
Area Under the Plasma Concentration Time Curve From 0 to the End of a Dosing Interval (AUCtau) QCC374: Day 112, Dose Level 0.12 mg	566 h*pg/mL Interval 566.0 to 566.0	—

SECONDARY outcome

Timeframe: 16 weeks

Population: Participants from the Pharmacodynamic (PD) analysis set, defined as all randomized participants who received at least one dose of study drug and one evaluable PD assessment, with data available for analysis were considered.

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.

Outcome measures

Outcome measures
Measure	Arm 1 n=3 Participants Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study 0.12mg -active patients will continue at the dose they finished on the QCC374X2201 study	Arm 2 Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol
Change From Baseline in Six Minute Walk Distance (6MWD)	452 Meter Standard Deviation 104.65	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm 1 n=1 Participants Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study 0.12mg -active patients will continue at the dose they finished on the QCC374X2201 study	Arm 2 Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol
Change in Tricuspid Annular Peak Systolic Velocity (TA S') at Week 16 (Day 112) Using Echocardiography	10.90 cm/s Standard Deviation NA NA: Not estimable due to insufficient number of participants	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm 1 n=1 Participants Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study 0.12mg -active patients will continue at the dose they finished on the QCC374X2201 study	Arm 2 Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol
Change From Baseline in RV Tei Index at Week 16 (Day 112) Using Echocardiography	0.84 Index Standard Deviation NA NA: Not estimable due to insufficient number of participants	—

SECONDARY outcome

Timeframe: 16 weeks

Outcome measures

Outcome measures
Measure	Arm 1 n=1 Participants Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study 0.12mg -active patients will continue at the dose they finished on the QCC374X2201 study	Arm 2 Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol
Change From Baseline in RV Fractional Area Change at Week 16 (Day 112) Using Echocardiography	23.91 Percentage change Standard Deviation NA NA: Not estimable due to insufficient number of participants	—

Adverse Events

QCC374 Arm 1

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

QCC374 Arm 2

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	QCC374 Arm 1 n=3 participants at risk Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study 0.12mg -active patients will continue at the dose they finished on the QCC374X2201 study	QCC374 Arm 2 n=2 participants at risk Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	33.3% 1/3 • through study completion an average of 4.5 months	0.00% 0/2 • through study completion an average of 4.5 months

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 8627788300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	QCC374 Arm 1 n=3 participants at risk Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study 0.12mg -active patients will continue at the dose they finished on the QCC374X2201 study	QCC374 Arm 2 n=2 participants at risk Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol
Blood and lymphatic system disorders Lymphopenia	33.3% 1/3 • through study completion an average of 4.5 months	0.00% 0/2 • through study completion an average of 4.5 months
Gastrointestinal disorders Abdominal pain upper	0.00% 0/3 • through study completion an average of 4.5 months	50.0% 1/2 • through study completion an average of 4.5 months
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • through study completion an average of 4.5 months	50.0% 1/2 • through study completion an average of 4.5 months
Gastrointestinal disorders Nausea	33.3% 1/3 • through study completion an average of 4.5 months	50.0% 1/2 • through study completion an average of 4.5 months
Gastrointestinal disorders Vomiting	33.3% 1/3 • through study completion an average of 4.5 months	50.0% 1/2 • through study completion an average of 4.5 months
General disorders Asthenia	0.00% 0/3 • through study completion an average of 4.5 months	50.0% 1/2 • through study completion an average of 4.5 months
General disorders Fatigue	0.00% 0/3 • through study completion an average of 4.5 months	50.0% 1/2 • through study completion an average of 4.5 months
Infections and infestations Nasopharyngitis	33.3% 1/3 • through study completion an average of 4.5 months	100.0% 2/2 • through study completion an average of 4.5 months
Injury, poisoning and procedural complications Sunburn	0.00% 0/3 • through study completion an average of 4.5 months	50.0% 1/2 • through study completion an average of 4.5 months
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • through study completion an average of 4.5 months	50.0% 1/2 • through study completion an average of 4.5 months
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • through study completion an average of 4.5 months	50.0% 1/2 • through study completion an average of 4.5 months
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • through study completion an average of 4.5 months	50.0% 1/2 • through study completion an average of 4.5 months
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/3 • through study completion an average of 4.5 months	100.0% 2/2 • through study completion an average of 4.5 months
Nervous system disorders Headache	33.3% 1/3 • through study completion an average of 4.5 months	100.0% 2/2 • through study completion an average of 4.5 months
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • through study completion an average of 4.5 months	50.0% 1/2 • through study completion an average of 4.5 months
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/3 • through study completion an average of 4.5 months	50.0% 1/2 • through study completion an average of 4.5 months
Vascular disorders Flushing	33.3% 1/3 • through study completion an average of 4.5 months	0.00% 0/2 • through study completion an average of 4.5 months