A Proof-of-mechanism Study of Multiple, Oral Doses of Fevipiprant (QAW039) in COPD Patients With Eosinophilia

NCT03810183 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: CQAW039E122012018-004267-32
• Study Type: interventional
• Target: 9
• Locations: 2 countries
• Sites: 4

Brief Summary

This was an exploratory, randomized, subject- and investigator-blind, placebo-controlled, parallel group, proof-of-mechanism study of multiple oral doses of fevipiprant (QAW039) in chronic obstructive pulmonary disease (COPD) patients with eosinophilia.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

QAW039; Chronic obstructive pulmonary disease; COPD; sputum; eosinophillic; eosinophilia; prostaglandin D2 receptor; DP2; CRTh2; fevipiprant

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Sputum Eosinophil Percentage Based on Log-10 Transformed Scale at Week 6

  Sputum eosinophil percentage of the total cell count was obtained from induced sputum samples. Sputum was processed to include preparation of slides for differential cellular count. As sputum eosinophil percentage has been found to follow a log-normal distribution, the analysis of this outcome measure was based on log10-transformed scale. The baseline measurement was defined as sputum eosinophil percentage prior to the first dosing (on log10-transformed scale).

  Baseline, Week 6

Study Arms (2)

QAW039 450 mg

EXPERIMENTAL

QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet.

Drug: QAW039

Placebo

PLACEBO COMPARATOR

Placebo once daily for 6 weeks administered orally as a tablet.

Drug: Placebo

Interventions

QAW039 DRUG

QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet + Standard of Care

QAW039 450 mg

Placebo DRUG

Placebo once daily for 6 weeks administered orally as a tablet + Standard of Care

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acceptable and reproducible spirometry with post-bronchodilator FEV1/FVC \< 0.7 and post-bronchodilator FEV1≥ 30 and ≤ 80% of predicted at the screening and baseline visits (GOLD stage II or III COPD).
• Patients with a physician-diagnosed history of COPD for at least 1 year prior to screening visit, and a documented history of at least one COPD exacerbation within the year prior to screening visit and on a stable therapy regimen for COPD for at least 4 weeks prior to screening visit with inhaled glucocorticoid + one or more long acting bronchodilator.
• Current or ex-smokers who have a smoking history of at least 10 pack-years (10 pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years, or equivalent).
• Circulating eosinophils ≥ 300 cells/µL blood AND sputum eosinophils ≥ 3% of total cell count during screening period.

You may not qualify if:

• Patients with a past or current medical history of asthma.
• Patients with a past or current medical history of conditions other than COPD or allergic rhinitis that could result in elevated sputum eosinophils (e.g., asthma, hypereosinophilic syndrome, Churg-Strauss Syndrome). Patients with known parasitic infestation within 6 months prior to screening are also excluded.
• Patients who have had a respiratory tract infection or COPD worsening or systemic steroid use within 4 weeks prior to screening visit or between screening and randomization visits.
• Patients with history of concomitant chronic or severe pulmonary disease (e.g., sarcoidosis, interstitial lung disease, cystic fibrosis, tuberculosis). Exception: patients with concomitant mild or moderate pulmonary hypertension or bronchiectasis are permitted to participate.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective contraception (also called basic contraception)methods during the study.
• Patients on any statin therapy with a CK level \> 2 X ULN at screening.
• Patients who have a clinically significant laboratory abnormality at the screening visit including (but not limited to):
• Total white blood cell count \<2500 cells/uL
• AST or ALT \> 2.0 X ULN or total bilirubin \> 1.3 X ULN
• Estimated Glomerular Filtration Rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation or Bedside Schwartz equation \<55 mL/minute/1.73 m2.
• Patients with any of the following cardiac related concerns:
• A resting QTcF (Fridericia) ≥450 msec (male) or ≥460 msec (female) at screening visit
• A history of familial long QT syndrome or known family history of Torsades de Pointe
• Receiving any medications or other agents known to prolong the QT interval
• patients with a history of moderate or severe uncontrolled tachyarrhythmias

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (4)

Novartis Investigative Site

Frankfurt, 60596, Germany

Location

Novartis Investigative Site

Hamburg, 20354, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Bradford, West Yorkshire, BD9 6RJ, United Kingdom

Location

Related Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Eosinophilia

Interventions

fevipiprant

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This was a subject and investigator-blinded study. Subjects, investigators and all site staff remained blinded to study treatment throughout the study. The identity of the treatments was concealed by the use of study drugs that were all identical in packaging, labeling, schedule of administration, appearance, and odor. The sponsor could be unblinded to the study treatment at any time, especially in case of a safety concern.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2019
• First Posted: January 18, 2019
• Study Start: May 21, 2019
• Primary Completion: January 16, 2020
• Study Completion: January 16, 2020
• Last Updated: October 8, 2021
• Results First Posted: January 25, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); DE (3)