Trial Outcomes & Findings for A Study to Establish the Efficacy of QBX258 in Patients With Moderate to Severe Asthma (NCT NCT01479595)

NCT ID: NCT01479595

Last Updated: 2016-08-01

Results Overview

The ACQ consists of 7 questions assessing symptoms, rescue medication use and lung function. Except for lung function (FEV1), each question was scored on a 7-point scale where 0 = no impairment and 6 = maximum impairment. Scores ranged between 0 totally controlled to 6 (severely uncontrolled). Participants with a score below 1.0 are considered to have adequately controlled asthma. Participants with a score above 1.0 were considered not to be well controlled. A negative change from baseline indicates improvement.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 65 participants
• Primary outcome timeframe: Baseline and 12 weeks
• Results posted on: 2016-08-01

Participant Flow

Participants were assigned to either QBX258 or placebo in a 2:1 ratio. Randomization was done by stratification of Q576R.

Participant milestones

Measure	QBX258 Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.
Overall Study STARTED	44	21
Overall Study PK Analysis Set	42	0
Overall Study Per Protocol Analysis Set	41	20
Overall Study COMPLETED	42	19
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Measure	QBX258 Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.
Overall Study Protocol deviation	0	1
Overall Study Adverse Event	2	1

Baseline Characteristics

A Study to Establish the Efficacy of QBX258 in Patients With Moderate to Severe Asthma

Baseline characteristics by cohort

Measure	QBX258 n=44 Participants Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo n=21 Participants Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.	Total n=65 Participants Total of all reporting groups
Age, Continuous	42.5 Years STANDARD_DEVIATION 11.71 • n=5 Participants	42.8 Years STANDARD_DEVIATION 13.54 • n=7 Participants	42.6 Years STANDARD_DEVIATION 12.22 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	11 Participants n=7 Participants	34 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	10 Participants n=7 Participants	31 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: Participants from the per-protocol analysis set were considered for the analysis. Only participants who had both baseline and week 12 values were included in the analysis.

The ACQ consists of 7 questions assessing symptoms, rescue medication use and lung function. Except for lung function (FEV1), each question was scored on a 7-point scale where 0 = no impairment and 6 = maximum impairment. Scores ranged between 0 totally controlled to 6 (severely uncontrolled). Participants with a score below 1.0 are considered to have adequately controlled asthma. Participants with a score above 1.0 were considered not to be well controlled. A negative change from baseline indicates improvement.

Outcome measures

Measure	QBX258 n=41 Participants Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo n=19 Participants Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.
Change From Baseline in Asthma Control Questionnaire (ACQ) Score	-0.513 score on a scale Standard Error 0.0970	0.001 score on a scale Standard Error 0.1487

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Participants from the per-protocol analysis set were considered for the analysis. Only participants who had both baseline and week 12 values were included in the analysis.

FEV1 was assessed using central spirometry according to the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines.

Outcome measures

Measure	QBX258 n=41 Participants Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo n=19 Participants Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.
Change in Forced Expiratory Volume in One Second (FEV1)	0.076 Liters Standard Error 0.0528	0.050 Liters Standard Error 0.0770

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Participants from the per-protocol analysis set were considered for the analysis. Only participants who had both baseline and week 12 values were included in the analysis.

The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments that are most important to patients with asthma. It consists of 4 domains: symptoms, emotions., exposure to environmental stimuli and activity limitation.

Patients were asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale. The scale ranges from 1 to 7. The overall AQLQ score was the mean response to all 32 questions. Higher scores represent better outcomes.

Outcome measures

Measure	QBX258 n=40 Participants Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo n=19 Participants Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.
Change in Asthma Quality of Life Questionnaire (AQLQ) Score	0.580 score on a scale Standard Error 0.1294	0.468 score on a scale Standard Error 0.1878

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: No analysis was performed on the collected data with the eDiary device due to overall poor data quality (values were obtained that were not physiologically possible) and high variability. Therefore, there is no data to present for this outcome measure.

Morning and evening PEFs were recorded on an electronic diary (e-diary). PEF was assessed twice daily approximately 12 hours apart and the measurements were recorded in the e-diary.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Participants from the per-protocol analysis set were considered for the analysis. Only participants who had both baseline and week 12 values were included in the analysis.

Maximum expiratory flow was assessed using central spirometry according to the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines.

Outcome measures

Measure	QBX258 n=41 Participants Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo n=19 Participants Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.
Change From Baseline in Maximum Expiratory Flow	0.099 L/sec Standard Deviation 0.4270	0.025 L/sec Standard Deviation 0.3000

SECONDARY outcome

Timeframe: 12 weeks

Population: All randomized participants

Anti-QAX576 and anti-VAK694 antibodies in serum were analyzed.

Outcome measures

Measure	QBX258 n=44 Participants Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo n=21 Participants Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.
Number of Participants With Anti-QAX576 Antibodies or Anti-VAK694 Antibodies	2 Participants	2 Participants

SECONDARY outcome

Timeframe: days 1 (pre-dose and 2 hours post-dose), 15, 29 (pre-dose and 2 hours post-dose), 43, 57 (pre-dose and 2 hours post-dose), 71, 85 (pre-dose and 2 hours post-dose), 99, 113, 141, 183

Population: Participants from the per-protocol analysis set were considered for the analysis. Only participants who had week 12 values were included in the analysis.

Blood samples were obtained to measure Cmax,ss.

Outcome measures

Measure	QBX258 n=40 Participants Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss) of the QAX576 Analyte Q576R SNP stratum: QQ (n=21)	169000 ng/mL Standard Deviation 47000	—
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss) of the QAX576 Analyte Q576R SNP stratum: RR/QR (n=19)	184000 ng/mL Standard Deviation 85000	—
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss) of the QAX576 Analyte QBX258 (n=40)	176000 ng/mL Standard Deviation 67300	—

SECONDARY outcome

Timeframe: days 1 (pre-dose and 2 hours post-dose), 15, 29 (pre-dose and 2 hours post-dose), 43, 57 (pre-dose and 2 hours post-dose), 71, 85 (pre-dose and 2 hours post-dose), 99, 113, 141, 183

Population: Participants from the per-protocol analysis set were considered for the analysis. Only participants who had week 12 values were included in the analysis.

Blood samples were obtained to measure Cmax,ss.

Outcome measures

Measure	QBX258 n=40 Participants Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss) of the VAK694 Analyte Q576R SNP stratum: QQ (n=21)	56.7 ug/mL Standard Deviation 8.90	—
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss) of the VAK694 Analyte Q576R SNP stratum: RR/QR (n=19)	58.6 ug/mL Standard Deviation 14.9	—
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss) of the VAK694 Analyte QBX258 (n=40)	57.6 ug/mL Standard Deviation 12.0	—

SECONDARY outcome

Timeframe: days 1 (pre-dose and 2 hours post-dose), 15, 29 (pre-dose and 2 hours post-dose), 43, 57 (pre-dose and 2 hours post-dose), 71, 85 (pre-dose and 2 hours post-dose), 99, 113, 141, 183

Population: Participants from the per-protocol analysis set were considered for the analysis. Only participants who had week 12 values were included in the analysis.

Blood samples were obtained to measure Cmin,ss.

Outcome measures

Measure	QBX258 n=40 Participants Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.
Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin,ss) of the QAX576 Analyte Q576R SNP stratum: QQ (n=21)	37500 ng/mL Standard Deviation 11900	—
Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin,ss) of the QAX576 Analyte Q576R SNP stratum: RR/QR (n=19)	32200 ng/mL Standard Deviation 9930	—
Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin,ss) of the QAX576 Analyte QBX258 (n=40)	35000 ng/mL Standard Deviation 11200	—

SECONDARY outcome

Timeframe: days 1 (pre-dose and 2 hours post-dose), 15, 29 (pre-dose and 2 hours post-dose), 43, 57 (pre-dose and 2 hours post-dose), 71, 85 (pre-dose and 2 hours post-dose), 99, 113, 141, 183

Population: Participants from the per-protocol analysis set were considered for the analysis. Only participants who had week 12 values were included in the analysis.

Blood samples were obtained to measure Cmin,ss.

Outcome measures

Measure	QBX258 n=40 Participants Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.
Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin,ss) of the VAK694 Analyte Q576R SNP stratum: QQ (n=21)	10.7 ug/mL Standard Deviation 2.69	—
Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin,ss) of the VAK694 Analyte Q576R SNP stratum: RR/QR (n=19)	9.83 ug/mL Standard Deviation 2.94	—
Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin,ss) of the VAK694 Analyte QBX258 (n=40)	10.3 ug/mL Standard Deviation 2.81	—

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: Participants from the per-protocol analysis set were considered for the analysis. Only participants who had both baseline and week 12 values were included in the analysis.

FeNO was assessed as a measure of airway inflammation. An FeNO machine was used to obtain the FeNO measurements. FeNO measurements were obtained prior to the spirometry assessments.

Outcome measures

Measure	QBX258 n=36 Participants Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo n=15 Participants Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.
Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)	-3.67 parts per billion (ppb) Standard Error 3.580	2.21 parts per billion (ppb) Standard Error 5.393

Adverse Events

QBX258

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	QBX258 n=44 participants at risk Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo n=21 participants at risk Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.
Pregnancy, puerperium and perinatal conditions ABORTION	0.00% 0/44	4.8% 1/21
Respiratory, thoracic and mediastinal disorders LARYNGEAL OEDEMA	2.3% 1/44	0.00% 0/21

Other adverse events

Measure	QBX258 n=44 participants at risk Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Placebo n=21 participants at risk Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.
Gastrointestinal disorders NAUSEA	6.8% 3/44	0.00% 0/21
Gastrointestinal disorders VOMITING	6.8% 3/44	0.00% 0/21
Infections and infestations NASOPHARYNGITIS	9.1% 4/44	9.5% 2/21
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	4.5% 2/44	9.5% 2/21
Nervous system disorders HEADACHE	11.4% 5/44	4.8% 1/21
Respiratory, thoracic and mediastinal disorders ASTHMA	6.8% 3/44	14.3% 3/21

Additional Information

Study Director

Novartis

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
• Publication restrictions are in place

Restriction type: OTHER