A Multi-Center, Randomized, Double Blind, Placebo-Controlled, ‘add-on’ study to investigate the efficacy and safety of 24 weeks intravenous treatment with QAX576 in patients (=18-75 years) with persistent asthma not adequately controlled with inhaled corticosteroids and long acting ß2-agonists

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2009-011590-32-BE
• Date of registration: 18/03/2010
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A Multi-Center, Randomized, Double Blind, Placebo-Controlled, ‘add-on’ study to investigate the efficacy and safety of 24 weeks intravenous treatment with QAX576 in patients (=18-75 years) with persistent asthma not adequately controlled with inhaled corticosteroids and long acting ß2-agonists
• Scientific title: A Multi-Center, Randomized, Double Blind, Placebo-Controlled, ‘add-on’ study to investigate the efficacy and safety of 24 weeks intravenous treatment with QAX576 in patients (=18-75 years) with persistent asthma not adequately controlled with inhaled corticosteroids and long acting ß2-agonists
• Date of first enrolment: 12/05/2010
• Target sample size: 256
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011590-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, Germany

Contacts

• Name: Clinical Trial Information desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed written informed consent before any assessment is performed, including any adjustments to asthma medication prior to Visit 2.
2. Male and female adult patients aged = 18 -75 years.
3. Female patients must be:
a. surgically sterilized at least 6 months prior to study participation (documentation of
sterilization must be provided) or
b. postmenopausal (no regular bleeding for at least 1 year), postmenopausal status must be confirmed by plasma FSH level of > 40IU/L at Visit 2
Note: A pregnancy test will be done on all female subjects regardless of reported
reproductive status at specified time points throughout the study.
5. Body mass index (BMI) must be within the range of 18 to 39 inclusive. For tables see Appendix 3.
6. Asthma, = 1 years duration diagnosed according to GINA guidelines (National Institute of Health, National Heart, Lung and Blood Institute, 2007)
7. Daily treatment with > 500µg BDP (>250µg b.i.d.), or equivalent, plus a LABA (b.i.d) (GINA step 4/5 therapy) for = 3 months prior to Visit 2, that has been stable for at least 4 weeks prior to Visit 2.
8. Asthma which is not adequately controlled on current treatment, as demonstrated by an Asthma Control Questionnaire (ACQ) score of > 1.5 at the end of the screening period (Juniper et al, 2006).
9. FEV1 of = 40% and = 80% of the predicted normal value for the patient, after withholding bronchodilators 1.
• To be included in the induced sputum sub study patients must have an FEV1= 55%
predicted at Visits 2 and 3.
10. Patients with demonstrated or documented increase of = 12% in FEV1 over their baseline value within 30 minutes of inhaling up to 400/360 µg of salbutamol / albuterol via an MDI after withholding bronchodilators 1,2 (the reversibility test).
11. Compliance with Electronic Peak Flow/ ediary device during the screening period* (at the investigators judgment the screening period can be extended to collect 14 days of acceptable ePEF/ediary data)
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Who have smoked or inhaled tobacco products within the 6 month period prior to Visit 2, or who have a smoking history of greater than 10 pack years, (defined as the number of packs of 20 cigarettes smoked per day multiplied by number of years the patient smoked).
2. Diagnosed with COPD as defined by the GOLD guidelines (Global Initiative for Chronic Obstructive Lung Disease 2008).
3. Who have had an asthma attack/exacerbation requiring a change in maintenance ICS or OCS treatment, or a short burst of systemic corticosteroids, within 6 weeks prior to Visit 2.
4. Who have had a respiratory tract infection within 6 weeks prior to Visit 2.
5. Who have a medical history (within the 3 months prior to Visit 1) that might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study.
6. 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 or INR of more than 1.5x ULN at Visit 2.
7. With history of renal disease or creatinine level above the ULN at Visit 2.
8. With fasting triglycerides over 300 mg/dl (3.39 mmol/L) at Visit 2.
9. With active cancer or a history of cancer with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). Localized basal cell carcinoma (without metastases) of the skin is acceptable.
10. With a history of schistosomiasis, or stool examination positive for ova or parasites (at Visit 2), or travel to an area endemic with schistosomiasis (in the 6 months prior to Visit 2), including but not limited to Southeast and Southwest Asia, South America and Africa. Travel to these areas must not be planned until at least 6 months after the last dose.
11. With a history of immunodeficiency diseases or hepatitis B or C.
12. With a history of hypersensitivity to any ingredients of the study drugs, or drugs related to QAX576 (e.g. monoclonal antibodies, polyclonal gamma globulin, polysorbates).
13. Who have had live attenuated vaccinations within 30 days prior to screening visit 2 or during the screening period1.
14. Treatments for asthma and allied conditions: the following medications must not be used prior to Visit 2 for at least the minimum washout period specified below or at any time during the study: • Omalizumab or other monoclonal antibody treatment within 4 months prior to Visit 2 • Methotrexate, gold salts, cyclosporin, troleandomycin: 3 months of Visit 2. • Short acting anti-cholinergics within 8 hours prior to Visit 2 • Long acting anti-cholinergics within 7 days prior to Visit 2.
15. Maintenance Immunotherapy (desensitization) for allergies is allowed if maintenance dose has been administered for at least 3 months prior to Visit 2, and is expected to remain unchanged throughout the course of the study.
16. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives prior to Visit 2, whichever is longer.
17. Patients that take acetaminophen (paracetamol) chronically, i.e. more than 1 g/day for more than 3 out of 7 days, or more than 2 g/ day for more than 1 day out of 7 days.
18. With a known history of non-compliance to medication or who are unable or unwilling to use Electronic Peak Flow with ediary device or perform spirometry measurements.
19. Patients that do not maintain regular day/night, waking/sleeping cycles (e.g. night shift workers will be excluded).
20. Patients with a h

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

persistent moderate to severe asthma patients not adequately controlled with inhaled corticosteroids and long acting ß2-agonists
MedDRA version: 13.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Name: NA
Product Code: QAX576
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: QAX576
Other descriptive name: NA
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 6.0-mg/kg
Pharmaceutical form of the placebo: Powder and solvent for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: Assess the efficacy of QAX576compared to placebo when added to existing asthma therapy with respect to the Asthma Control Questionnaire (ACQ) score following 24 weeks treatment in patients with inadequately controlled moderate to severe persistent asthma. Inadequate control is defined as an ACQ score of >1.5 at the end
of the screening period (Juniper et al, 2006).

Secondary Objective: To assess the efficacy of QAX576A compared to placebo when added to existing asthma therapy with respect to:
1. The incidence rate of clinically significant asthma exacerbations over 24 weeks treatment (defined as a worsening of asthma leading to oral or parenteral corticosteroid use; or for patients using regular maintenance oral corticosteroids (OCS) at screening, an increase in OCS use or parenteral corticosteroid use)
2. The number/percent of patients with an absolute change from baseline in the ACQ score of at least 1.25 at week 24 3. The total symptom scores (sum of night time, morning, day time symptom scores) as measured by mean daily total symptom score recorded between clinic visits at weeks 22 -24

Additional secondary objectives are detailled in the protocol

Primary end point(s): The primary objective is to determine if QAX576 is superior to placebo with respect to
Asthma Control Questionnaire (ACQ, Juniper, 1999 Juniper, 1999) following 24 weeks of treatment for patients with inadequately controlled moderate to severe persistent asthma.

Secondary ID(s)

CQAX576A2207

2009-011590-32-DE

Source(s) of Monetary Support

Novartis Pharma AG