Study of Efficacy and Safety of LOU064 in Inadequately Controlled Asthma Patients

NCT03944707 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: CLOU064D122012018-003609-24
• Study Type: interventional
• Target: 76
• Locations: 5 countries
• Sites: 19

Brief Summary

This was a proof-of-concept study to evaluate the efficacy of LOU064 in patients with inadequately controlled asthma. All subjects were randomized with 3:2 ratio to receive LOU064 100 mg once daily or LOU064 matching placebo for 12 weeks with standard background therapy of budesonide 80 µg/formoterol 4.5 µg two inhalations twice a day (b.i.d).

Conditions

Asthma

Keywords

asthma; LOU064

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Pre-dose FEV1 at Week 12

  FEV1 (forced expiratory volume in one second) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. Pre-dose FEV1 is defined as average of the two FEV1 measurements taken 45 min and 15 min pre-dose. The baseline pre-dose FEV1 is defined as the average of the FEV1 measurements performed 45 min and 15 min prior to dosing on Day 1. A positive change from baseline in pre-dose FEV1 is considered a favorable outcome. Change from baseline in pre-dose FEV1 was analyzed using a Bayesian model for repeated measures, adjusting for effects of treatment\*visit interaction and baseline pre-dose FEV1. A weakly informative prior was considered for the placebo response.

  Baseline, Week 12

Secondary Outcomes (7)

• Maximum Observed Blood Concentrations (Cmax) of LOU064 at Steady State

  pre-dose, 0.5, 1, 2, 3 and 4 hours after dosing on Days 15 and 85

• Time to Reach Maximum Blood Concentrations (Tmax) of LOU064 at Steady State

  pre-dose, 0.5, 1, 2, 3 and 4 hours after dosing on Days 15 and 85

• Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24h) of LOU064 at Steady State

  pre-dose, 0.5, 1, 2, 3 and 4 hours after dosing on Days 15 and 85

• Change From Baseline in Asthma Symptom Questionnaire-5 Score (ACQ-5) at Week 12

  Baseline, Week 12

• Change From Baseline in Mean Morning and Mean Evening Peak Expiratory Flow (PEF)

  Baseline, Weeks 9-12

Study Arms (2)

LOU064

EXPERIMENTAL

LOU064 100 mg once daily orally

Drug: LOU064 100 mg

Placebo

PLACEBO COMPARATOR

Placebo once daily orally

Drug: Placebo

Interventions

LOU064 100 mg DRUG

LOU064 100 mg once daily orally administered as two 50 mg capsules

LOU064

Placebo DRUG

Placebo once daily administered orally as capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female adult patients aged ≥ 18 to ≤ 70 years at screening.
• Patients must weigh at least 40 kg to participate in the study, and must have a body mass index (BMI) \<35 kg/m2. BMI = Body weight (kg) / \[Height (m)\]2 at screening
• Patients with a physician-diagnosed history of asthma (according to GINA 2018) for a period of at least 6 months prior to screening.
• Patients who have been treated with:
• Medium or high dose inhaled corticosteroids (ICS), or
• ICS plus long-acting beta agonist (LABA), or
• ICS plus leukotriene receptor antagonist (LTRA), or
• ICS plus long-acting beta agonist (LABA) and long lasting muscarinic antagonist (LAMA) for at least 1 month prior to screening and on the same doses of the above mentioned medications over at least 2 weeks prior to start of the run-in period.
• Post-bronchodilator reversibility of FEV1 ≥ 12% and ≥ 200 mL at screening. If reversibility is not demonstrated at screening, then two additional attempts are permitted (one at the run-in visit and the last one during the run-in period between the run-in visit and baseline visit if needed)
• Spirometry with pre-bronchodilator FEV1 ≥ 40% of predicted (at screening and baseline) and ≤ 85% of predicted at the baseline visit.
• ACQ-5 score ≥ 1.5 at baseline visit
• ≥ 80% compliance with peak expiratory flow measurement and recording of symptoms in the eDiary during the run-in period.

You may not qualify if:

• Patients who have had an asthma exacerbation requiring systemic corticosteroids, hospitalization, or emergency room visit within 6 weeks prior to screening or during the screening period.
• Patients who have smoked or inhaled any substance other than asthma medications within the 6 month period prior to screening, or who have a smoking history of greater than 10 pack years (e.g. 10 pack years = 1 pack/day x 10 years or ½ pack/day x 20 years, etc.).
• History of life-threatening asthma event such as significant hypercarbia (pCO2 \> 45 mmHg), endotracheal intubation, non-invasive positive pressure ventilation (NIPPV), respiratory arrest, or seizure as a result of asthma.
• Patients with chronic lung diseases other than asthma, including (but not limited to) chronic obstructive pulmonary disease, clinically significant bronchiectasis, sarcoidosis, interstitial lung disease, cystic fibrosis, Churg-Strauss syndrome, allergic broncho-pulmonary aspergillosis, or clinically significant chronic lung diseases related to a history of tuberculosis or asbestosis.
• History or current diagnosis of ECG abnormalities indicating significant risk of safety for subjects participating in the study such as:
• Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker
• History of familial long QT syndrome or known family history of Torsades de Pointes
• Resting heart rate (physical exam or 12 lead ECG) \< 50 bpm at screening
• Resting QTcF ≥ 450 msec (male) or ≥ 460 msec (female) at screening or inability to determine the QTcF interval
• Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of study
• At screening and/or run-in period, any severe, progressive or uncontrolled, acute or chronic, medical or psychiatric condition, or other factors such as abnormal vital signs, ECG or physical findings, or clinically relevant abnormal laboratory values, that in the judgment of the investigator may increase the risk associated with study participation/treatment or may interfere with interpretation of study results, and thus would make the patient inappropriate for entry into or continuing the study.
• Major surgery within 8 weeks prior to screening or surgery planned prior to end of study.
• History of live attenuated vaccine within 6 weeks prior to randomization or requirement to receive vaccinations at any time during the study.
• Hematology parameters at screening:
• Hemoglobin: \< 10 g/dl

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (19)

Novartis Investigative Site

Denver, Colorado, 80230, United States

Location

Novartis Investigative Site

North Dartmouth, Massachusetts, 02747, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63141, United States

Location

Novartis Investigative Site

Raleigh, North Carolina, 27607, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1056ABJ, Argentina

Location

Novartis Investigative Site

CABA, Buenos Aires, C1425BEN, Argentina

Location

Novartis Investigative Site

Rosario, Santa Fe Province, S2000DBS, Argentina

Location

Novartis Investigative Site

Rosario, Santa Fe Province, S2000JKR, Argentina

Location

Novartis Investigative Site

Berlin, 10787, Germany

Location

Novartis Investigative Site

Berlin, 12159, Germany

Location

Novartis Investigative Site

Frankfurt, 60596, Germany

Location

Novartis Investigative Site

Hamburg, 20354, Germany

Location

Novartis Investigative Site

Hanover, 30173, Germany

Location

Novartis Investigative Site

Biaystok, Poland, 15-430, Poland

Location

Novartis Investigative Site

Grudziądz, 86-300, Poland

Location

Novartis Investigative Site

Krakow, 30033, Poland

Location

Novartis Investigative Site

Poznan, 60 823, Poland

Location

Novartis Investigative Site

Saint Petersburg, 196143, Russia

Location

Novartis Investigative Site

Ulyanovsk, 432063, Russia

Location

Related Links

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

MeSH Terms

Conditions

Asthma

Interventions

remibrutinib

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System 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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2019
• First Posted: May 9, 2019
• Study Start: July 18, 2019
• Primary Completion: April 27, 2020
• Study Completion: April 27, 2020
• Last Updated: October 11, 2021
• Results First Posted: April 27, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share

Locations

AR (4); RU (2); US (4); DE (5); PL (4)