To evaluate the efficacy, safety and tolerability of QGE031 (24 mg, 72 mg, 240 mg s.c. q4w) compared to placebo on top of SoC in atopic patients with asthma.
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Rate of severe asthma exacerbations during 52 weeks of treatment
Secondary outcome
Key secondary objectives
* To evaluate the efficacy of QGE031 (24 mg, 72 mg, 240 mg s.c. q4w) compared
to placebo on top of SoC in all asthma patients (atopic and non-atopic) who are
not adequately controlled by medium- or high-dose ICS plus LABA with or without
OCS on the reduction in rate of severe asthma exacerbations during 52 weeks of
treatment.
* To evaluate the efficacy of QGE031 (24 mg, 72 mg, 240 mg s.c. q4w) compared
to placebo on top of SoC in non-atopic patients with asthma who are not
adequately controlled by medium- or high-dose ICS plus LABA with or without OCS
on the reduction in rate of severe asthma exacerbations during 52 weeks of
treatment.
Other secondary objectives
* Exacerbation (except listed above)
* ACQ5, 6, 7 scores
* ACD scores
* FEV1, FVC, FEV1/FVC
* PEF
ACQ5,6,7 scores
ACD scores
FEV1, FVC, FEV1/FVC
Background summary
QGE031 is a so-called monoclonal antibody, a drug that has been developed
especially in the laboratory to inhibit the production of immunoglobulin E or
IgE. IgE plays a role in allergic reactions. QGE031 resembles the drug Xolair
(omalizumab), which is registered in the Netherlands for the treatment of
asthma. Preclinical research showed QGE031 a more effective inhibitor than
omalizumab which resulted in less allergic skin reactions. QGE031 has not been
studied in patients with asthma. Through this study, the efficacy and safety of
52 weeks of treatment administered subcutaneously QGE031 (every 4 weeks) in
patients with asthma is assessed.
Study objective
To evaluate the efficacy, safety and tolerability of QGE031 (24 mg, 72 mg, 240
mg s.c. q4w) compared to placebo on top of SoC in atopic patients with asthma.
Study design
A multicenter, randomised, placebocontrolled study to assess efficacy and
safety of QGE031 (13 s.c. 4-weekly injections) in patients with asthma. It
consists of 4 phases:
A screening epoch of up to 2 weeks duration during which patients who have
given informed consent are assessed for study eligibility.
A 4 week run-in epoch where baseline data are collected. At the end of this
epoch, eligible patients are randomized to double-blind treatment.
A 52 week double blind treatment epoch during which patients receive study drug
every 4 weeks.
A follow-up epoch with the final visit occurring 20 weeks after the last
treatment epoch visit (Visit 215) to allow for a complete wash out of the drug
and assess persistency of efficacy and/or any
rebound.
Total duration of study is approx. 1.5 years.
Intervention
13 x 4-weekly s.c. injection 24 mg, 72 mg or 240 mg QGE031 or placebo
Study burden and risks
Burden:
13 s.c. injections, 4-weekly.
physical Examination: 6x
Assessment length 1x, weight 3x, bloodpressure and pulse 6x
Blood collection: 13 x, 5-32 ml per visit
Optional pharmacogenetic/-genomic blood collection: 4x (5 ml per visit),
moreover nasal swab collection: 4x
Urine collection: 7x
female subjects: Pregnancy test: 18x (3x in serum, 15x in urine)
Stool/feces sample collection: 1x
Spirometry:14x
Teversibility test:1x
Skin prick tests: 1x
Completion of registration injection site reactions: Throughout treatment period
PEF and completion of diaries: Throughout duration study
FeNO: 9x
ECG:10x
Completion of 4 questionnaires: 11 x (not all 4 at each visit)
Risks:
Adverse Events QGE031 and risks/burden studyprocedures
Known Adverse events QGE031:
- Most common reported: Hives, approx. 2 hrs post injection. Disappeared
quickly after treatment of this allergic reaction.
- Allergic reactions (e.g., rash, swelling of throat and/or tongue) and some
which on rare occasion may be severe (e.g., very low blood pressure and
difficulty with breathing). The risk for a severe allergic reaction caused by
the study drug is not known yet, however there have been no occurrences so far
and the risk is considered low.
- Risks at s.c. injection site: Pain, swelling, redness and bruising.
Risks/burden studyprocedures:
- Venapuncture (blood collection): Fainting, pain and/or bruising. Rarely,
there may be a small blood clot or infection at the site of the needle puncture.
- Skin Prick tests: Local redness, swelling and itching. Extremely rare, an
allergic reaction involving the entire body with itching, hives, wheezing or in
severe cases, low blood pressure, swelling of the throat and/or difficulty
breathing.
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
Inclusion criteria
- Male and female adult patients aged * 18 to * 75 years.
- Patients with a diagnosis of asthma according to GINA 2014 for a period of at least 12 months prior to Visit 1.
- Daily treatment with medium- or high-dose ICS plus LABA (b.i.d. or equivalent) for * 3 months prior to Visit 1 (stable regimen at least 4 weeks prior to Visit 1). If the patients are treated with OCS (* 10 mg/day of prednisone or equivalent), the regimen should be stable at least 4 weeks prior to Visit 1 (Appendix 3 for the definition of corticosteroid dose).
- A documented history of at least two asthma exacerbations in the 12 months prior to Visit 1 that had required treatment with systemic corticosteroids (SCS) for at least 3 continuous days or a depo-injectable corticosteroids, or that required hospitalization or ER visit.
- FEV1 of * 40% and * 80% of the predicted normal value for the patient, after withholding bronchodilators at Visit 101. Withholding period of bronchodilators prior to spirometry: SABA for * 6 hrs and LABA (or FDC of ICS/LABA) for * 24 hrs, SAMA for * 8 hrs, LAMA for * 24 hrs. If FEV1 is between * 35 to 40% or 80 to * 85% of the patient*s predicted normal value, a one-time re-testing is allowed. Re-assessment of % predicted FEV1 should be done in an ad-hoc visit to be scheduled on a date that would provide sufficient time to receive confirmation from the spirometry data central reviewer before randomization.
- Patients must demonstrate an increase in FEV1 of * 12% and 200 mL within 30 minutes after administration of 400 µg salbutamol/albuterol (or equivalent dose) at Visit 1.
If reversibility is not proven at Visit 101, patients may be permitted to enter the study with historical evidence of reversibility within 5 years prior to Visit 1.
- Body mass index (BMI) must be within the range of * 18 and * 45 kg/m2.
- Asthma which is not adequately controlled on current treatment, as demonstrated by an ACQ5 score of *1.5 at Visit 101 and at Visit 102.
- The atopic status will be assessed at Visit 1 by using *Skin Prick Test (SPT)* and blood multi-allergen testing (ImmunoCAP Phadiatop, Phadia AB)* during V1.
Exclusion criteria
- Patients who experience an asthma attack/exacerbation requiring a short burst of SCSs during screening and run-in, they may be rescreened 6 weeks after recovery from the attack/exacerbation
- Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1
- Patients who experience a respiratory tract infection during screening and run-in, they may be rescreened 4 weeks after recovery from the respiratory tract infection
- History of life-threatening asthma in the previous ten years, including a history of significant hypercarbia (pCO2 > 45 mmHg), prior intubation (endotracheal and NIPPV), respiratory arrest, or seizures as a result of asthma
- Patients who have smoked or inhaled tobacco products within the 6 month period prior to Visit 1, or who have a smoking history of greater than 10 pack years (e.g. 10 pack years = 1 pack/day x 10 years or * pack/day x 20 years, etc.).
- Patients who are participating in the active phase of a supervised pulmonary rehabilitation program unless the patient is on a maintenance program that has been ongoing for at least 3 months.
- Patients who have not achieved acceptable spirometry results at Visit 101 in accordance with ATS/ERS criteria for acceptability and repeatability (rescreening allowed only once).
- Patients with chronic lung diseases other than asthma.
- History of generalized urticaria or who have an acute urticaria episode at time of screening or during run-in. If patients experience an acute urticaria episode during screening or run-in, they may be rescreened after recovery from the urticaria.
- Patients with a stool examination positive for ova/parasites at Visit 101. If a stool test is positive for Blastocystis hominis (a non-pathogenic parasite) and the patient is asymptomatic, the patient can continue the study without screening failure.
Design
Recruitment
Medical products/devices used
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 | EUCTR2014-003155-57-NL |
| ClinicalTrials.gov | NCT02336425 |
| CCMO | NL52415.058.15 |