Display again
SNCTP000004646 | EUCTR2019-000325-49 | BASEC2021-01281

Untersuchung der Wirkweise von QBW251 bei Patienten mit chronisch obstruktiver Lungenerkrankung (COPD) im Rahmen einer randomisierten, placebo-kontrollierten, doppelblinden Studie mit zwei parallelen Behandlungsgruppen

Data source: BASEC (Imported from 27.01.2022), WHO (Imported from 18.01.2022)
Changed: 13.01.2022
Disease category: Respiratory diseases (non cancer)

Brief description of trial (Data source: BASEC)

Es handelt sich um eine internationale Studie mit 100 Studienteilnehmern. In dieser Studie wird die Wirkungsweise, sowie die Sicherheit und Wirksamkeit eines neuen Wirkstoffs (QBW251) gegenüber Placebo zusätzlich zur inhalativen Standardtherapie über einen Beobachtungszeitraum von 12 Wochen untersucht.
Der Wirkungsort des Prüfpräparats ist der CFTR (“cystic fibrosis transmembrane conductance regulator”) -Kanal. Das Prüfpräparat soll die Funktionsweise dieses Kanals verstärken. Es soll untersucht werden, ob durch diese Funktionsverstärkung Entzündungsprozesse in der Lunge und im Organismus, sowie die bakterielle Besiedlung in der Lunge reduziert werden können. Entzündungsprozesse und bakterielle Besiedlung werden als mögliche Treiber der Atemwegsobstruktion – und -zerstörung, der Umbauprozesse in den Atemwegen und der akuten Krankheitsschübe (Exazerbationen) diskutiert.
Bei den Studienteilnehmern handelt es sich um erwachsene Patienten und Patientinnen, ab 40 Jahren, mit mässig schwerer bis schwerer COPD. Die COPD ist dabei gekennzeichnet durch chronische Bronchitis (Auswurf und Husten), einer Rauchhistorie oder aktuellem Nikotinkonsum von 10 Packungsjahren (z.B. eine Packung mit 20 Zigaretten pro Tag für 10 Jahre oder eine halbe Packung pro Tag über einen Zeitraum von 20 Jahren). Die Studienteilnehmer sollten des Weiteren mindestens eine schwere bzw. zwei mittelschwere COPD-Krankheitsschübe (Exazerbationen) seit Januar 2019 erfahren haben. Des Weiteren sollen die Studienteilnehmer eine bestimmte Grenze für den Biomarker Fibrinogen (u.a. Marker für Entzündungsprozesse) und eine bakterielle Besiedlung im Sputum (Auswurf) aufweisen.

Health conditions investigated (Data source: BASEC)

Chronic Obstructive Pulmonary Disease (COPD)

Health conditions (Data source: WHO)

Chronic obstructive pulmonary disease
MedDRA version: 21.1Level: LLTClassification code 10029972Term: Obstructive airways disease (chronic)System Organ Class: 100000004855;Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

Die Studie umfasst drei Teile:
1. Voruntersuchungsphase (um festzustellen, ob Sie für die Studie in Frage kommen) von bis zu 6 Wochen.
2. Verblindete Behandlungsphase (Dauer 12 Wochen, Beginn der Behandlung, danach 4 Besuche im Studienzentrum und ein telefonischer Termin)
3. Sicherheitsnachbeobachtung nach Ende der Behandlungsphase von 4 Wochen mit einem Besuch im Studienzentrum und einem telefonischen Termin

Insgesamt beläuft sich die Dauer der Studie pro Studienteilnehmer auf 19 Wochen.

Interventions (Data source: WHO)


Product Code: QBW251
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not yet defined
Current Sponsor code: QBW251
Other descriptive name: CFTR potentiator
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Criteria for participation in trial (Data source: BASEC)

• Patienten und Patientinnen mit stabiler COPD GOLD Stadium 2-3 (GOLD Guidelines 2019, Lungenfunktionsparameter: post-bronchodilator. FEV1/FVC < 0.70, post-bronchodilator. FEV1 ≥ 30% und FEV1 pred. < 80%), mit stabiler Therapie (ICS/LABA; LABA/LAMA; ICS/LABA/LAMA; seit 3 Monaten unverändert), mit mindestens zwei moderaten bzw. einer schweren Exazerbation ab Januar 2019.
• COPD- Typ chron. Bronchitis (Husten mit Auswurf an den meisten Tage (mehr als 50% aller Tage) für mindestens 3 aufeinander folgende Monate, sowie Nachweis bakterieller Besiedlung im Sputum (Bakterienlast >80,000 CFU/mL, mit Nachweis von mindestens einem der folgenden Erreger: H influenzae, H parainfluenzae, P aeruginosa, S pneumoniae, S aureus, Moraxella catarrhalis, Enterobacteriaceae, Stenotrophomonas maltophilia, Burkholderia species, Achromobacter species oder jedes andere potentiell pathogene Bakterium).
• Patienten mit einer Plasma Fibrinogen Konzentration ≥ 320 mg/dL

Exclusion criteria (Data source: BASEC)

• Patienten mit einem Long-QT Syndrome in der Vorgeschichte oder Patienten, welche im Rahmen der Voruntersuchungen ein verlängertes QTcF Intervall aufweisen (Fridericia method; QTcF >450 ms bei Männern, >460 ms bei Frauen) und anderen klinisch signifika nten abnormalen Veränderungen des EKGs.
• Patienten mit Begleiterkrankungen, die in Ermessen des Prüfarztes, die Untersuchungen zur Wirksamkeit und Sicherheit, sowie die Sicherheit des Patienten in der Studie beeinträchtigen. Dabei handelt es sich um folgende Erkrankungen: klinisch signifikante Nierenleiden, kardiovaskuläre Erkrankungen (instabile ischämische Herzerkrankung, Linksherzinsuffizienz NYHA Class III/IV, Myokardinfarkt), neurolog., endokrinolog., immunolog., psychiatrische, gastrointestinale oder hämatolog. Erkrankungen oder unkontrollierter Typ II Diabetes). Ferner sind Patienten mit einer Krebserkrankung innerhalb der letzten fünf Jahre (mit Ausnahme eines Basalzellkarzinoms der Haut) von der Studienteilnahme ausgeschlossen.
• Patienten mit einer Lebererkrankung in der Vorgeschichte oder welche eine Behandlung für eine Lebererkrankung erhalten (inkl. akute Hepatitis, Zirrhose, Leberversagen, nicht abschliessend).

Inclusion/Exclusion Criteria (Data source: WHO)

Inclusion criteria:
•Patients who have signed an Informed Consent Form prior to initiation of any study-related procedure.
•Male and female adults aged =40 years at screening.
•Patients with stable COPD, stages GOLD 2-4, according to the current GOLD strategy (GOLD 2019) at screening.
•Patients with a post-bronchodilator FEV1/FVC < 0.70 at screening
•Patients with airflow limitation indicated by a post-bronchodilator FEV1 = 30% and FEV1 < 80% of the predicted normal at Screening who must have had at least 2 documented moderate or at least 1 documented severe exacerbation(s) in the 12 months prior to study entry.
•Patients with sputum bacterial load (log10=105 CFU/mL) with at least one strain of potentially pathogenic
microorganism at screening (H influenzae, H parainfluenzae, P aeruginosa, S pneumoniae, S aureus, Moraxella catarrhalis, Enterobacteriaceae).
•Patients who have been treated with a combination of LABA/LAMA or LABA/ICS or LABA/LAMA/ICS at a stable dose for the last 3 months prior to screening.
COPD patients are allowed to stay on macrolides as background therapy if they have bronchiectasis as a secondary diagnosis and if they are treated with them at a stable dose 3 months before screening.
•Patients with plasma fibrinogen level =350 mg/dL at screening.
•A COPD Assessment Test (CAT) score of at least 10 at screening.
•Current or ex-smokers who have a smoking history of at least 10 pack years at screening. (e.g. 10 pack years = 1 pack/day x 10 years, or 0.5 pack/day x 20 years) at screening.
•Patients featuring chronic bronchitis, defined as productive cough that occurs on most days (defined as >50% of days) during at least 3 consecutive months in the year prior to screening, as assessed by documentation of patient recollection(anamnesis) or documented in patients' records.
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 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
•Patients with a history of long-QT syndrome or whose QTcF interval at screening (Fridericia method) is prolonged (QTcF >450 ms in males, >460 ms in females).
•Patients who have a clinically significant ECG abnormality before randomization.
•Clinical laboratory values abnormalities (including Gamma GT, AST, ALT, total bilirubin or creatinine) considered as clinically significant in the opinion of the Investigator at screening.
•Patients who have clinically significant renal, cardiovascular (such as but not limited to unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, myocardial infarction), neurological, endocrine, immunological, psychiatric, gastrointestinal, or hematological abnormalities, which could interfere with the assessment of the efficacy and safety of the study treatment, or patients with uncontrolled Type II diabetes.
•Patients with a history or current treatment for hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or an AST/ALT of more than 1.5x ULN or abnormal PT/INR at screening.
•Patients with a history of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. Patients with a history of cancer and 5 years or more disease free survival time may be included in the study by agreement with Novartis Medical Monitor on a case-by-case basis.
•Patients who develop a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization during screening. Re-screening is permitted after a minimum of 2 weeks after the resolution of the COPD exacerbation (i.e. 2 weeks after the stop of SOC therapy for exacerbation).
•Patients who have had a respiratory tract infection within 4 weeks prior to screening. If a respiratory tract infection occurs during screening, patients can be re-screened after a minimum of 2 weeks after resolution of the respiratory tract infection.
•Patients with history of asthma or any other clinically relevant lung diseases.
•Patients with suspected active pulmonary tuberculosis or currently being treatment for active pulmonary tuberculosis.
Note: Patients with a history of pulmonary tuberculosis can be enrolled if they meet the following requirements: history of appropriate drug treatment followed by negative imaging results within 12 months prior to screening suggesting low probability of recurrent active tuberculosis.
•Patients with pulmonary lobectomy, lung volume reduction surgery, bronchoscopic lung volume reductions, or lung transplantation.
•Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the trial. Participation in a maintenance program is permitted. Note: the supervised pulmonary rehabilitation program as a maintenance program has to be ongoing for at least 3 months at the time of enrollment.
•Patients with a body mass index (BMI) of more than 40 kg/m2.
•Pregnant or nursing (lactating) women where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
•Women of childbearing potential defined as all women physiologically capable of becoming pregnant,unless they are using acceptable effective methods of contracepti

Further information on the trial in WHO primary registry

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-000325-49

Further information on the trial from WHO database (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2019-000325-49-DE

Further information on trial

Date trial registered

09.04.2020

Incorporation of the first participant

09.04.2020

Recruitment status

Authorised-recruitment may be ongoing or finished

Academic title (Data source: WHO)

A randomized, subjects and investigator blinded, placebo controlled parallel group study to assess the mode of action of QBW251 in patients with Chronic Obstructive Pulmonary Disease (COPD)

Type of trial (Data source: WHO)

Interventional clinical trial of medicinal product

Design of the trial (Data source: WHO)

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 (Data source: WHO)

Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): yesTherapeutic confirmatory - (Phase III): noTherapeutic use (Phase IV): no

Primary end point (Data source: WHO)

Main Objective: To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on fibrinogen plasma concentration.;Secondary Objective: •To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on:
a)sputum bacterial load
b)airway structure and function
c)COPD patients symptom burden changes
d)health status
e)changes in health-related quality of life
f)COPD exacerbations
g)clinical symptoms, cough and sputum
h)pharmacokinetics
i)spirometry
•To assess the safety and tolerability of QBW251 in patients with COPD;Primary end point(s): Change from baseline in fibrinogen plasma concentration.;Timepoint(s) of evaluation of this end point: 12 weeks of treatment

Secundary end point (Data source: WHO)

Secondary end point(s): •Change from baseline in total bacteria load of colony forming units (CFU/mL) of potentially pathogenic microorganisms in sputum.
•Change from baseline in airway wall and lumen parameters along with extent of global and regional air trapping, as measured by HRCT.
•Change from baseline in COPD Assessment Test (CAT) questionnaire.
•Changes from baseline in the Euro Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) questionnaire.
•Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total and domain scores.
•Time to first COPD exacerbation, Proportion of patients with exacerbations and Annualized rate of exacerbations as defined by EXACT-PRO questionnaire.
•Change from baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) domain scores.
•Assessment of safety and tolerability (ECG intervals, vital signs, standard clinical laboratory Evaluations, adverse Events)
•Assessment of drug exposure (Ctrough collected at pre-dose and Cmax at post-dose +3hr) on Day 1, Day 28, Day 56 and Day 84. Cmax and AUC post-dose (+1hr, +2hr, +3hr, +4hr, +6hr, +8hr) on Day 1 and Day 28 in subset of patient population
•Change from baseline in trough FEV1, FVC, and FEV1/FVC.;Timepoint(s) of evaluation of this end point: 12 weeks of treatment

Contact information (Data source: WHO)

Novartis Pharma AG

Trial results (Data source: WHO)

Results summary

A randomized, subjects and investigator blinded, placebo controlled parallel group study to assess the mode of action of QBW251 in patients with Chronic Obstructive Pulmonary Disease (COPD)

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Basel, St. Gallen, Zurich

Countries (Data source: WHO)

Switzerland might not appear as site of trial if it has not yet been entered as such in the WHO primary registry.
Germany, United Kingdom

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Bianca Fay
+41 79 330 7663
bianca.fay@novartis.com

Contact for general information (Data source: WHO)

Medizinischer Infoservice (MCC)
Roonstrasse 25
Novartis Pharma GmbH
 +49 911 273-12100 
infoservice.novartis@novartis.com

Contact for scientific information (Data source: WHO)

Medizinischer Infoservice (MCC)
Roonstrasse 25
Novartis Pharma GmbH
 +49 911 273-12100 
infoservice.novartis@novartis.com

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

Novartis Pharma AG

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Ethikkommission Nordwest- und Zentralschweiz EKNZ

Date of authorisation by the ethics committee

29.07.2021

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2021-01281

Secondary ID (Data source: WHO)

CQBW251B2202