Dose-range Finding Efficacy and Safety Study for QBW251 in COPD Patients

NCT ID: NCT04072887

Last Updated: 2023-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 974 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-12
• Study Completion Date: 2022-02-01

Brief Summary

This clinical study was designed to support the dose selection for future studies by evaluating efficacy and safety of different QBW251 doses in Chronic obstructive pulmonary disease (COPD) patients with chronic bronchitis and a history of exacerbations, compared to placebo, when added to a triple inhaled therapy of LABA, LAMA and ICS.

Detailed Description

This study used a 6 treatment arm, parallel-group, randomized, double-blind study design. 974 male and female COPD patients were randomized into the trial. The study consisted of four distinct study periods:

• Screening (Weeks -3 to -2): Participants underwent a screening period of 1 week where were assessed for eligibility and tapered off disallowed medications.
• Run-in (Days -14 to 1): Subsequently, participants entered the run-in period of up to 2 weeks to establish baseline values for symptom assessments, to standardize the COPD background therapy (triple combination LABA/LAMA/ICS), and to complete eligibility assessments.
• Treatment (Day 1 to Week 24): Eligible participants moved into the Day 1 visit where they were stratified according to their smoking status (current or ex-smoker) and severity of airflow limitation (FEV1 ≥ 30% to < 50% and ≥ 50% to < 80%) and then randomized into 1 of 6 treatment arms with a randomization ratio of 2:2:1:1:1:2 (450 mg b.i.d., 300 mg b.i.d., 150 mg b.i.d., 75 mg b.i.d., 25 mg b.i.d., placebo). The treatment period consisted of 24 weeks, during which the participant returned to the site for regular visits (Day 1 - Week 24). QBW251 450 mg arm was discontinued early based on a pre-defined pharmacokinetic exposure stopping rule.
• Follow-up (Weeks 25-28): Upon completion of the treatment period, participants were followed up for safety assessments for 30 days.

Conditions

Pulmonary Disease, Chronic Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

QBW251 450 mg

QBW251 was orally administered 450 mg b.i.d for 24 weeks

Group Type: EXPERIMENTAL

QBW251

Intervention Type: DRUG

QBW251 oral capsules (450, 300, 150, 75 and 25 mg) of identical appearance to ensure blinding administered twice a day (b.i.d) for 24 weeks

COPD maintenance background therapy

Intervention Type: DRUG

Combination of fluticasone furoate, vilanterol and umeclidinium bromide

QBW251 300 mg

QBW251 was orally administered 300 mg b.i.d for 24 weeks

Group Type: EXPERIMENTAL

QBW251

Intervention Type: DRUG

QBW251 oral capsules (450, 300, 150, 75 and 25 mg) of identical appearance to ensure blinding administered twice a day (b.i.d) for 24 weeks

COPD maintenance background therapy

Intervention Type: DRUG

Combination of fluticasone furoate, vilanterol and umeclidinium bromide

QBW251 150 mg

QBW251 was orally administered 150 mg b.i.d for 24 weeks

Group Type: EXPERIMENTAL

QBW251

Intervention Type: DRUG

QBW251 oral capsules (450, 300, 150, 75 and 25 mg) of identical appearance to ensure blinding administered twice a day (b.i.d) for 24 weeks

COPD maintenance background therapy

Intervention Type: DRUG

Combination of fluticasone furoate, vilanterol and umeclidinium bromide

QBW251 75 mg

QBW251 was orally administered 75 mg b.i.d for 24 weeks

Group Type: EXPERIMENTAL

QBW251

Intervention Type: DRUG

QBW251 oral capsules (450, 300, 150, 75 and 25 mg) of identical appearance to ensure blinding administered twice a day (b.i.d) for 24 weeks

COPD maintenance background therapy

Intervention Type: DRUG

Combination of fluticasone furoate, vilanterol and umeclidinium bromide

QBW251 25 mg

QBW251 was orally administered 25 mg b.i.d for 24 weeks

Group Type: EXPERIMENTAL

QBW251

Intervention Type: DRUG

QBW251 oral capsules (450, 300, 150, 75 and 25 mg) of identical appearance to ensure blinding administered twice a day (b.i.d) for 24 weeks

COPD maintenance background therapy

Intervention Type: DRUG

Combination of fluticasone furoate, vilanterol and umeclidinium bromide

Placebo

Placebo was orally administered b.i.d for 24 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo oral capsules administered twice a day for 24 weeks

COPD maintenance background therapy

Intervention Type: DRUG

Combination of fluticasone furoate, vilanterol and umeclidinium bromide

Interventions

QBW251

QBW251 oral capsules (450, 300, 150, 75 and 25 mg) of identical appearance to ensure blinding administered twice a day (b.i.d) for 24 weeks

Intervention Type: DRUG

Placebo

Placebo oral capsules administered twice a day for 24 weeks

Intervention Type: DRUG

COPD maintenance background therapy

Combination of fluticasone furoate, vilanterol and umeclidinium bromide

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and female COPD patients aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure.
• Current or ex-smokers who have a smoking history of at least 10 pack years.
• Patients who have been treated with a triple combination of LABA/LAMA/ICS for the last 3 months prior to screening.
• Patients featuring chronic bronchitis

Exclusion Criteria

• Patients who have had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization, or a respiratory tract infection in the 4 weeks prior to screening, or between screening and randomization.
• Patients with any documented history of asthma, or with an onset of chronic respiratory symptoms, including a COPD diagnosis, prior to age 40 years.
• Patients with a body mass index (BMI) of more than 40 kg/m2.
• Use of other investigational drugs (approved or unapproved) within 30 days or 5 half-lives prior to screening, or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations.
• Pregnant or nursing (lactating) women, and women of childbearing potential not willing to use acceptable effective methods of contraception during study participation.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Novartis Investigative Site

Andalusia, Alabama, United States

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Los Angeles, California, United States

Novartis Investigative Site

Westminster, California, United States

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Ormond Beach, Florida, United States

Novartis Investigative Site

Sarasota, Florida, United States

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Winter Park, Florida, United States

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Florence, Kentucky, United States

Novartis Investigative Site

Crowley, Louisiana, United States

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New Orleans, Louisiana, United States

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Zachary, Louisiana, United States

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Livonia, Michigan, United States

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Edina, Minnesota, United States

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Minneapolis, Minnesota, United States

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Saint Charles, Missouri, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Charlotte, North Carolina, United States

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Gastonia, North Carolina, United States

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Shelby, North Carolina, United States

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Columbus, Ohio, United States

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Medford, Oregon, United States

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El Paso, Texas, United States

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Houston, Texas, United States

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McKinney, Texas, United States

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Midlothian, Virginia, United States

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Berazategui, Buenos Aires, Argentina

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Mar del Plata, Buenos Aires, Argentina

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Concepción del Uruguay, Entre Ríos Province, Argentina

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Rosario, Santa Fe Province, Argentina

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Rosario, Santa Fe Province, Argentina

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Ciudad Autonoma de Bs As, , Argentina

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Mendoza, , Argentina

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Mendoza, , Argentina

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Salta, , Argentina

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Santa Fe, , Argentina

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South Brisbane, Queensland, Australia

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Clayton, Victoria, Australia

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Footscray, Victoria, Australia

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Spearwood, Western Australia, Australia

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Feldbach, , Austria

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Grieskirchen, , Austria

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Thalheim bei Wels, , Austria

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Erpent, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Sherwood Park, Alberta, Canada

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Saint-Charles-Borromée, Quebec, Canada

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Sainte-Foy, Quebec, Canada

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Zipaquirá, Cundinamarca, Colombia

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Liberec, Czech Republic, Czechia

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Ostrava Poruba, Czech Republic, Czechia

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Teplice, Czech Republic, Czechia

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Varnsdorf, , Czechia

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Aalborg, , Denmark

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Copenhagen, , Denmark

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Hvidovre, , Denmark

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Montpellier, Herault, France

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Lyon, , France

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Pessac, , France

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Reims, , France

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Berlin, , Germany

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Berlin, , Germany

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Berlin, , Germany

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Frankfurt, , Germany

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Halle, , Germany

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Hamburg, , Germany

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Landsberg, , Germany

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Leipzig, , Germany

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Leipzig, , Germany

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Leipzig, , Germany

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Mainz, , Germany

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Marburg, , Germany

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Mittweida, , Germany

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Witten, , Germany

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Heraklion Crete, Greece, Greece

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Thessaloniki, GR, Greece

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Guatemala City, GTM, Guatemala

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Guatemala City, GTM, Guatemala

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Guatemala City, , Guatemala

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New Territories, Hong Kong, Hong Kong

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Pokfulam, Hong Kong, Hong Kong

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Budapest, , Hungary

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Gödöllő, , Hungary

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Komárom, , Hungary

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Makó, , Hungary

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Pécs, , Hungary

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Genova, GE, Italy

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Siena, SI, Italy

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Negrar, VR, Italy

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Nagoya, Aichi-ken, Japan

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Nagoya, Aichi-ken, Japan

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Fukuoka, Fukuoka, Japan

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Fukuoka, Fukuoka, Japan

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Kasuga, Fukuoka, Japan

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Koga, Fukuoka, Japan

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Yanagawa, Fukuoka, Japan

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Mizunami, Gifu, Japan

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Asahikawa, Hokkaido, Japan

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Sapporo, Hokkaido, Japan

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Naka-gun, Ibaraki, Japan

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Kawasaki, Kanagawa, Japan

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Sagamihara, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Matsusaka, Mie-ken, Japan

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Sendai, Miyagi, Japan

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Kawachi-Nagano, Osaka, Japan

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Kishiwada, Osaka, Japan

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Toyonaka, Osaka, Japan

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Chuo Ku, Tokyo, Japan

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Chuo-ku, Tokyo, Japan

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Chuo-ku, Tokyo, Japan

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Kodaira, Tokyo, Japan

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Setagaya-Ku, Tokyo, Japan

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Setagaya-ku, Tokyo, Japan

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Shinagawa, Tokyo, Japan

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Toshima Ku, Tokyo, Japan

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Yamagata, Yamagata, Japan

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Osaka, , Japan

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Eindhoven, , Netherlands

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Harderwijk, , Netherlands

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Lipa City, Batangas, Philippines

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Iloilo City, Iloilo, Philippines

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Bulacan, , Philippines

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Iloilo City, , Philippines

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Manila, , Philippines

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Grudziądz, , Poland

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Katowice, , Poland

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Zawadzkie, , Poland

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Bardejov, Slovak Republic, Slovakia

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Bojnice, Slovak Republic, Slovakia

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Humenné, Slovak Republic, Slovakia

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Poprad, , Slovakia

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Prešov, , Slovakia

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Spišská Nová Ves, , Slovakia

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Vyšné Hágy, , Slovakia

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Seoul, Seocho Gu, South Korea

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Daegu, , South Korea

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Incheon, , South Korea

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Marbella, Andalusia, Spain

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Alzira, Valencia, Spain

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Girona, , Spain

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Songkhla, Hat Yai, Thailand

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Khon Kaen, THA, Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Adana, , Turkey (Türkiye)

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Mersin, , Turkey (Türkiye)

Novartis Investigative Site

London, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Canada; Colombia; Czechia; Denmark; France; Germany; Greece; Guatemala; Hong Kong; Hungary; Italy; Japan; Netherlands; Philippines; Poland; Slovakia; South Korea; Spain; Thailand; Turkey (Türkiye); United Kingdom

References

Martinez FJ, Criner GJ, Gessner C, Jandl M, Scherbovsky F, Shinkai M, Siler TM, Vogelmeier CF, Voves R, Wedzicha JA, Bartels C, Bottoli I, Byiers S, Cardenas P, Eckert JH, Gutzwiller FS, Knorr B, Kothari M, Parlikar R, Tanase AM, Franssen FME. Icenticaftor, a CFTR Potentiator, in COPD: A Multicenter, Parallel-Group, Double-Blind Clinical Trial. Am J Respir Crit Care Med. 2023 Aug 15;208(4):417-427. doi: 10.1164/rccm.202303-0458OC.

Reference Type: DERIVED

PMID: 37411039 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-003197-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CQBW251B2201

Identifier Type: -

Identifier Source: org_study_id