The primary objective of Part 2 of this study is to determine the efficacy of pretreatment with CNTO 3157 compared with placebo in attenuating the respiratory manifestations of inoculation with HRV-16 in adult subjects with mild to moderate asthma.…
ID
Source
Brief title
Condition
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy in Part 2 will be assessed using standard assessments to evaluate
asthma treatments (eg, FEV1, ACQ). Although these standard assessments are
primarily meant to assess efficacy, changes in these assessments will also be
used to monitor safety throughout the study.
Efficacy evaluations will include spirometry (including FEV1, etc.), collection
of patient reported outcomes (ACQ), daily asthma symptom diaries collected on a
handheld electronic device (including the number of nocturnal awakenings,
rescue medication use, impact on activities, and PEF), and assessment of nasal
and ocular symptoms using TNOSS. These evaluations are widely accepted as
standard endpoints for demonstrating therapeutic efficacy in terms of reduction
of signs and symptoms of asthma. TNOSS will be used to evaluate the potential
effect of CNTO 3157 on nasal and ocular symptoms which often co exist in
subjects with asthma.
Secondary outcome
see general description of study parameters in paragraph: "primary study
parameters/outcome of the study"
Background summary
CNTO 3157 is a fully human, sequence-adapted, IgG4* monoclonal antibody (mAb)
that binds the extracellular domain (ECD) of human Toll-like receptor 3
(TLR3).
Exacerbations of asthma are frequently due to respiratory viral infections, in
particular those caused by human rhinoviruses (HRVs). While the underlying
mechanisms driving viral-induced exacerbations of asthma are not fully
understood, it is possible that activation of TLR3 by viral RNA could trigger
or enhance immune-mediated pathologies associated with exacerbations of
asthma.
Study objective
The primary objective of Part 2 of this study is to determine the efficacy of
pretreatment with CNTO 3157 compared with placebo in attenuating the
respiratory manifestations of inoculation with HRV-16 in adult subjects with
mild to moderate asthma.
The secondary objectives are to assess the safety, tolerability, PK, PD, and
immunogenicity of multiple IV administrations of CNTO 3157 compared with
placebo in adult subjects with mild to moderate asthma inoculated with HRV-16.
Study design
The study is randomized, multi-center, double-blind, parallel-design and
placebo controlled
In Part 2, the severity of an upper respiratory tract infection due to
inoculation with HRV-16 will be assessed
At the same time the efficacy will be assessed in part 2, using standard
assessments to evaluate asthma treatments (eg, FEV1, PEFR, ACQ).
An independent Data Monitoring Committee will be commissioned for this study.
Intervention
Subjects in Part 2 will receive either 4 IV infusions of placebo at Week 1,
Week 2, Week 3, and Week 4 (30 subjects), or 1 IV infusion of CNTO 3157 10
mg/kg at Week 1 followed by 3 infusions of 3 mg/kg of CNTO 3157 at Week 2, Week
3, and Week 4 (30 subjects). These infusions will also be administered over a
period of not less than 30 minutes. After the last infusion (within 24 to 72
hours) at Week 4, subjects will be inoculated with HRV-16.
Study burden and risks
This is described in the information for the patient in the paragraph: "Which
side effects can I expect?"
Summary from this paragraph:
Possible side effects from CNTO 3157:
Headache
Swelling of the nasal passages
Back pain
Generalized pain
Nausea
Diarrhea
Cough
Sore throat
Toothache
Most commond side effects of HRV-16 include:
Runny nose
Sneezing
Nasal Congestion
Rapid heartbeat
Ringing in the ears
Bronchitis
Jaw pain
Cough
Respiratory tract congestion
Tiredness
Possibility allergic reactions, possibility infusion reactions, risk vaccins
and risks study procedures are also described in this paragraph
Dr. Paul Janssenweg 150
Tilburg 5026 RH
NL
Dr. Paul Janssenweg 150
Tilburg 5026 RH
NL
Listed location countries
Age
Inclusion criteria
Be 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 75 years of age, inclusive at the time of signing the informed consent
-Have a body mass index (BMI) of 19 to 40 kg/m2 inclusive.
- Have a physician documented diagnosis of asthma for at least 6 months prior to Screening Visit 2.
- Have objective evidence of asthma by fulfilling 1 of the following 4 criteria below. Only
1 of these 4 criteria below needs to be fulfilled:
• An increase in FEV1 of 12% or greater and at least a 200 mL within 30 minutes after administration of up to 8 puffs of a short-acting β2-agonist (SABA) at Screening Visit 2,
• -documented increase in FEV1 of 12% or greater and at least a 200 mL within 30 minutes after administration of up to 8 puffs of a SABA within 36 months before Screening Visit 1
• -documented airway reactivity to histamine (PC20 histamine < or equal 8 mg/mL) or methacholine (PC20 methacholine < or equal 16 mg/mL) within 36 months prior to screening visit 1
• Airway reactivity to histamine (PC20 histamine < or equal 8mg/ml) or methacholine (PC20 methacholine < or equal 16 mg/ml assessed between screening visit 2 and prior to day 1.
- Have stable asthma based on physician assessment at Screening Visit 2.
• Permitted concomitant medications for asthma must have been at a stable dose for the 4 weeks prior to Screening Visit 1.
- Have a prebronchodilator forced expiratory volume in the first second (FEV1) >= 65% of predicted normal value at Screening Visit 2.
Exclusion criteria
- Has a history of any other chronic lung disease, including chronic obstructive pulmonary disease (COPD), bronchiolitis, bronchiectasis, allergic bronchopulmonary aspergillosis (mycosis), occupational asthma, sleep apnea, pulmonary hypertension, or any other obstructive pulmonary disease, liver or renal insufficiency; significant unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances, or other body system disorders that are clinically significant in the opinion of the investigator.
- Has ever had an episode of life-threatening asthma defined as respiratory arrest or requiring intubation for asthma.
- Has been hospitalized (for greater than 24 hours) due to asthma in the 5 years prior to Screening Visit 1.
- Has experienced an asthma exacerbation in the 12 weeks prior to Screening Visit 1 requiring management with systemic steroids.
- Is receiving high dose ICS (>500 µg/day to fluticasone or equivalent). Use of low or medium dose ICS (<=500 µg/day fluticasone or equivalent) with or without permitted controller medications e.g LABA, LTRA is allowed.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-005369-19-NL |
| ClinicalTrials.gov | NCT01704040 |
| CCMO | NL42552.056.12 |