A Study to Evaluate Efficacy and Safety of ADC3680 in Subjects With Inadequately-Controlled Asthma

A Randomised, Double Blind, Placebo-Controlled, Multi-Centre, Parallel Group Study to Evaluate the Efficacy and Safety of ADC3680 Administered Once Daily as an Add-On Therapy to Inhaled Corticosteroids and When Co-Administered With Montelukast in Subjects With Inadequately-Controlled Asthma.

This randomised, double-blind, placebo-controlled study will evaluate the efficacy and safety of ADC3680 administered once daily as an add-on therapy to inhaled corticosteroids and when co-administered with montelukast in patients with inadequately-controlled asthma. Patients will be randomised to 3 Arms to receive ADC3680, placebo or montelukast.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: ADC3680; Drug: Placebo; Drug: montelukast

Detailed Description

This is a multi-centre, randomised, placebo-controlled, double blind, parallel group 3-arm study (including montelukast as an active comparator) designed to compare the efficacy and safety of a once daily dose of ADC3680 with placebo in subjects with inadequately-controlled asthma despite receiving a low to moderate dose of an ICS controller therapy, over a 10 week treatment period. At the end of the 10 week treatment period open label montelukast (10 mg) will be added to ADC3680 and placebo arms for a two week extension period to assess whether efficacy of ADC3680 is enhanced by the addition of montelukast compared with montelukast alone. The montelukast arm will continue with 10 mg montelukast alone.

• Study Type: Interventional
• Enrollment (Actual): 248
• Phase: Phase 2

Contacts and Locations

Study Locations

• Croatia
  • Cakovec, Croatia
    • Pulmagen Investigational Site
  • Sisak, Croatia
    • Pulmagen Investigational Site
  • Varazdin, Croatia
    • Pulmagen Investigational Site
  • Zagreb, Croatia
    • Pulmagen Investigational Site
• Czechia
  • Beroun, Czechia
    • Pulmagen Investigational Site
  • Brno, Czechia
    • Pulmagen Investigational Site
  • Havlickuv Brod, Czechia
    • Pulmagen Investigational Site
  • Holesov, Czechia
    • Pulmagen Investigational Site
  • Jaromer, Czechia
    • Pulmagen Investigational Site
  • Neratovice, Czechia
    • Pulmagen Investigational Site
  • Svitavy, Czechia
    • Pulmagen Investigational Site
  • Teplice, Czechia
    • Pulmagen Investigational Site
  • Tremosna, Czechia
    • Pulmagen Investigational Site
• Germany
  • Augsburg, Germany
    • Pulmagen Investigational Site
  • Bad Worishofen, Germany
    • Pulmagen Investigational Site
  • Berlin, Germany
    • Pulmagen Investigational Site
  • Bonn, Germany
    • Pulmagen Investigational Site
  • Deggingen, Germany
    • Pulmagen Investigational Site
  • Dresden, Germany
    • Pulmagen Investigational Site
  • Geesthacht, Germany
    • Pulmagen Investigational Site
  • Hagen, Germany
    • Pulmagen Investigational Site
  • Hamburg, Germany
    • Pulmagen Investigational Site
  • Hannover, Germany
    • Pulmagen Investigational Site
  • Marburg, Germany
    • Pulmagen Investigational Site
  • Schwerin, Germany
    • Pulmagen Investigational Site
  • Teuchem, Germany
    • Pulmagen Investigational Site
  • Weyhe, Germany
    • Pulmagen Investigational Site
• Hungary
  • Balassagyarmat, Hungary
    • Pulmagen Investigational Site
  • Budapest, Hungary
    • Pulmagen Investigational Site
  • Kaposvar, Hungary
    • Pulmagen Investigational Site
  • Komlo, Hungary
    • Pulmagen Investigational Site
  • Pecs, Hungary
    • Pulmagen Investigational Site
  • Szazhalombatta, Hungary
    • Pulmagen Investigational Site
  • Szombathely, Hungary
    • Pulmagen Investigational Site
• Poland
  • Bialystok, Poland
    • Pulmagen Investigational Site
  • Bielsko Biala, Poland
    • Pulmagen Investigational Site
  • Bienkowka, Poland
    • Pulmagen Investigational Site
  • Bydgoszcz, Poland
    • Pulmagen Investigational Site
  • Kielce, Poland
    • Pulmagen Investigational Site
  • Krakow, Poland
    • Pulmagen Investigational Site
  • Lodz, Poland
    • Pulmagen Investigational Site
  • Olsztyn, Poland
    • Pulmagen Investigational Site
  • Ostrow Wilekopolski, Poland
    • Pulmagen Investigational Site
  • Poznan, Poland
    • Pulmagen Investigational Site
  • Proszowice, Poland
    • Pulmagen Investigational Site
  • Skierniewice, Poland
    • Pulmagen Investigational Site
  • Tarnow, Poland
    • Pulmagen Investigational Site
  • Warszawa, Poland
    • Pulamgen Investigational Site
  • Wilkowice-Bystra, Poland
    • Pulmagen Investigational Site
  • Wroclaw, Poland
    • Pulmagen Investigational Site
  • Zabrze, Poland
    • Pulmagen Investigational Site
  • Zgierz, Poland
    • Pulmagen Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Pulmagen Investigational Site
  • California
    • Huntington Beach, California, United States, 922647
      • Pulmagen Investigational Site
    • Riverside, California, United States
      • Pulmagen Investigational Site
    • Rolling Hills, California, United States, 90274
      • Pulmagen Investigational Site
    • San Jose, California, United States
      • Pulmagen Investigational Site
  • Colorado
    • Colorado Springs, Colorado, United States
      • Pulmagen Investigational Site
  • Connecticut
    • Waterbury, Connecticut, United States, 6708
      • Pulmagen Investigational Site
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Pulmagen Investigational Site
  • Idaho
    • Eagle, Idaho, United States, 83616
      • Pulmagen Investigational Site
  • Maryland
    • Nottingham, Maryland, United States, 21236
      • Pulmagen Investigational Site
  • Minnesota
    • Plymouth, Minnesota, United States
      • Pulmagen Investigational Site
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
      • Pulmagen Investigational Site
  • New Jersey
    • Bricktown, New Jersey, United States
      • Pulmagen Investigational Site
  • North Carolina
    • Clemmons, North Carolina, United States, 27012
      • Pulmagen Investigatinal Site
  • Ohio
    • Canton, Ohio, United States
      • Pulmagen Investigational Site
    • Cincinnati, Ohio, United States, 45231
      • Pulamgen Investigational Site
    • Maumee, Ohio, United States
      • Pulmagen Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Pulmagen Investigational Site
    • Tulsa, Oklahoma, United States, 74136
      • Pulmagen Investigational Site
  • Oregon
    • Medford, Oregon, United States
      • Pulmagen Investigational Site
    • Portland, Oregon, United States
      • Pulmagen Investigational Site
  • Rhode Island
    • East Providence, Rhode Island, United States
      • Pulmagen Investigational Site
    • Warwick, Rhode Island, United States, 02886
      • Pulmagen Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States
      • Pulmagen Investigational Site
    • Fort Mill, South Carolina, United States, 29707
      • Pulmagen Investigational Site
  • Texas
    • Arlington, Texas, United States
      • Pulmagen Investigational Site
    • Austin, Texas, United States
      • Pulmagen Investigational Site
    • Houston, Texas, United States, 77099
      • Pulmagen Investigational Site
    • Killeen, Texas, United States
      • Pulmagen Investigational Site
    • Waco, Texas, United States
      • Pulmagen Investigational Site
    • Woodway, Texas, United States, 76712
      • Pulmagen Investgational Site
  • Utah
    • Draper, Utah, United States
      • Pulmagen Investigational Site
  • Washington
    • Seattle, Washington, United States
      • Pulmagen Investigational Site
    • Tacoma, Washington, United States, 98405
      • Pulmagen Investigational Site
  • Wisconsin
    • Greenfield, Wisconsin, United States
      • Pulmagen Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women aged 18 years to 50 years (inclusive)
• Diagnosis of asthma (GINA 2011) including a demonstration of reversible airway obstruction
• Pre-bronchodilator FEV1 value ≥ 40% and ≤ 85% of the predicted normal value at baseline
• A score of 1.5 or greater on the Asthma Control Questionnaire at baseline
• Daily use of low to moderate dose of ICS (equivalent to budesonide ≤ 800 µg per day)
• Prescribed a short-acting inhaled bronchodilator as reliever therapy for relief of symptoms
• A peripheral blood eosinophil count ≥ 0.25 x 109/L
• Non-smoker or former smoker who has not smoked in the last six months
• Body mass index (BMI) ≥ 17 and ≤ 35 kg/m2
• Able to comply with the protocol requirements, instructions and restrictions
• Able to provide signed and dated written informed consent

Exclusion Criteria:

• Subjects with severe asthma exacerbation in the 4 weeks prior to consent
• Subjects with respiratory tract infection in the 4 weeks prior to consent
• Subjects with COPD or other relevant lung diseases
• Subjects with clinically significant condition which may compromise subject safety or interfere with study evaluation

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADC3680; ADC3680 oral once daily	Drug: ADC3680; ADC3680 for 12 weeks plus montelukast for the last 2 weeks of the dosing period
Placebo Comparator: Placebo; Placebo oral once daily	Drug: Placebo; Placebo for 12 weeks plus montelukast for the last 2 weeks of the dosing period
Active Comparator: montelukast; montelukast oral once daily	Drug: montelukast; montelukast for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Efficacy of ADC3680 compared with placebo in improving lung function (FEV1)	10 weeks
Adding montelukast to ADC3680 in improving lung function (FEV1)	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of ADC3680 compared with placebo on mean change in Asthma Control Questionnaire (ACQ) from baseline to Week 10		10 weeks
Efficacy of ADC3680 compared with placebo on mean change in trough pre-bronchodilator FEV1 % predicted from baseline to Week 2		2 weeks
Efficacy of ADC3680 compared with placebo on mean change in trough pre-bronchodilator FEV1 % predicted from baseline to Week 6		6 weeks
Efficacy of ADC3680 compared with placebo on mean change in trough pre-bronchodilator FEV1 % predicted from baseline to Week 10		10 weeks
Efficacy of ADC3680 compared with placebo on mean change in post-bronchodilator FEV1 from baseline to Week 10		10 weeks
Efficacy of ADC3680 compared with placebo on mean change in pre-bronchodilator PEF (in-clinic) from baseline to Week 2		2 weeks
Efficacy of ADC3680 compared with placebo on mean change in pre-bronchodilator PEF (in-clinic) from baseline to Week 6		6 weeks
Efficacy of ADC3680 compared with placebo on mean change in pre-bronchodilator PEF (in-clinic) from baseline to Week 10		10 weeks
Efficacy of ADC3680 compared with placebo on mean change in blood eosinophils from baseline to Week 10		10 weeks
Efficacy of ADC3680 compared with placebo on mean change in serum IgE from baseline to Week 10		10 weeks
Adding montelukast to ADC3680 on mean change in ACQ scores from Week 10 to Week 12		2 weeks
Adding montelukast to ADC3680 on mean change in trough pre-bronchodilator FEV1 % predicted from Week 10 to Week 12		2 weeks
Adding montelukast to ADC3680 on mean change in pre-bronchodilator PEF (in-clinic) from Week 10 to Week 12		2 weeks
Adding montelukast to ADC3680 on mean change in blood eosinophils from Week 10 to Week 12		2 weeks
Safety of ADC3680 compared to placebo	Safety evaluations will include incidence of Serious Adverse Events (from informed consent), severity & frequency of Adverse Events, change in laboratory values (haematology, clinical chemistry and urinalysis), change in vital signs (pulse, systolic and diastolic blood pressure), change in ECG and change in physical examination from baseline to week 10.	10 weeks
Safety of a 2 week administration of ADC3680 in combination with montelukast	Safety evaluations will include incidence of Serious Adverse Events, severity & frequency of Adverse Events, change in laboratory values (haematology, clinical chemistry and urinalysis), change in vital signs (pulse, systolic and diastolic blood pressure), change in ECG and change in physical examination from week 10 to week 12.	2 weeks

Collaborators and Investigators

• Sponsor: Pulmagen Therapeutics

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: November 9, 2012
• First Submitted That Met QC Criteria: November 20, 2012
• First Posted (Estimate): November 21, 2012

Study Record Updates

• Last Update Posted (Actual): October 6, 2017
• Last Update Submitted That Met QC Criteria: October 2, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Montelukast
• Other Study ID Numbers: ADC3680-07; 2012-003966-42 (EudraCT Number)