Trial Outcomes & Findings for A Study to Evaluate the Efficacy of MEDI-528 on Late Asthmatic Response With Atopic Asthma (NCT NCT00394654)

NCT ID: NCT00394654

Last Updated: 2013-12-11

Results Overview

Change from baseline (percent reduction) in mean maximum decline of forced expiratory volume in one second (FEV1) during LAR at 3 to 7 hours after an inhaled allergen challenge.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: Day 7
• Results posted on: 2013-12-11

Participant Flow

Thirty patients were entered into the study between 16Oct2006 and 15Aug2007 at 2 sites in Canada.

Treatment assignments were determined using a block randomization procedure with a 1:1 ratio through an interactive Web response system (IWRS). Patients who were randomized into the study but did not complete the second allergen challenge on Day 7 were replaced, unless the patient withdrew for safety reasons.

Participant milestones

Measure	PLACEBO	MEDI528 9 mg/kg MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Overall Study STARTED	15	15
Overall Study COMPLETED	13	15
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Measure	PLACEBO	MEDI528 9 mg/kg MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Overall Study Lost to Follow-up	1	0
Overall Study PARTICIPANT LEFT STDUY REGION	1	0

Baseline Characteristics

A Study to Evaluate the Efficacy of MEDI-528 on Late Asthmatic Response With Atopic Asthma

Baseline characteristics by cohort

Measure	PLACEBO n=15 Participants	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion	Total n=30 Participants Total of all reporting groups
Age Continuous	30.5 Years STANDARD_DEVIATION 9.6 • n=5 Participants	26.5 Years STANDARD_DEVIATION 7.8 • n=7 Participants	28.5 Years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 7

Population: All participants who were randomized into the study and completed the second allergen challenge on Day 7.

Change from baseline (percent reduction) in mean maximum decline of forced expiratory volume in one second (FEV1) during LAR at 3 to 7 hours after an inhaled allergen challenge.

Outcome measures

Measure	PLACEBO n=13 Participants Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=12 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Effect of MEDI-528 on Late Asthmatic Response (LAR) After Inhaled Allergen Challenge at Day 7	21.26 Percent Standard Deviation 69.288	-16.21 Percent Standard Deviation 61.788

PRIMARY outcome

Timeframe: Day 28

Population: All participants who were randomized into the study and completed the second allergen challenge on Day 7.

Change from baseline (percent reduction) in mean maximum decline of FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge.

Outcome measures

Measure	PLACEBO n=14 Participants Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=11 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 28	29.93 Percent Standard Deviation 46.646	-16.95 Percent Standard Deviation 123.256

PRIMARY outcome

Timeframe: Day 56

Population: All participants who were randomized into the study and completed the second allergen challenge on Day 7.

Change from baseline (percent reduction) in mean maximum decline of FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge.

Outcome measures

Measure	PLACEBO n=13 Participants Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=11 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 56	40.36 Percent Standard Deviation 45.123	31.85 Percent Standard Deviation 53.709

PRIMARY outcome

Timeframe: Day 7

Population: All participants who were randomized into the study and completed the second allergen challenge on Day 7.

Change from baseline (percent reduction) in mean maximum decline of area under the concentration-time curve (AUC) of the participants FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge.

Outcome measures

Measure	PLACEBO n=13 Participants Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=12 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 7	21.86 Percent Standard Deviation 94.34	-14.47 Percent Standard Deviation 82.43

PRIMARY outcome

Timeframe: Day 28

Population: All participants who were randomized into the study and completed the second allergen challenge on Day 7.

Change from baseline (percent reduction) in mean maximum decline of AUC of the participants FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge.

Outcome measures

Measure	PLACEBO n=14 Participants Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=11 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 28	2.91 Percent Standard Deviation 133.75	-13.09 Percent Standard Deviation 175.27

PRIMARY outcome

Timeframe: Day 56

Population: All participants who were randomized into the study and completed the second allergen challenge on Day 7.

Change from baseline (percent reduction) in mean maximum decline of AUC of the participants FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge.

Outcome measures

Measure	PLACEBO n=13 Participants Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=11 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 56	41.75 Percent Standard Deviation 65.49	51.91 Percent Standard Deviation 98.49

SECONDARY outcome

Timeframe: Days 0 - 126

Population: All subjects who received at least one dose of investigational product (MEDI-528 or placebo)

Number of participants experiencing adverse events (includes both adverse events and serious adverse events)

Outcome measures

Measure	PLACEBO n=15 Participants Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Incidence of Adverse Events	11 Participants	12 Participants

SECONDARY outcome

Timeframe: Days 0 - 126

Population: All subjects who received at least one dose of investigational product (MEDI-528 or placebo)

Number of participants experiencing serious adverse events

Outcome measures

Measure	PLACEBO n=15 Participants Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Incidence of Serious Adverse Events	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Days 0, 27, 55, 84, and 126

Population: All subjects who received at least one dose of investigational product (MEDI-528 or placebo)

Number of participants with ADA to MEDI-528

Outcome measures

Measure	PLACEBO n=15 Participants Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Incidence of Anti-drug Antibodies (ADA) to MEDI-528	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Days 0, 6, 7, 27, 55, 84, and 126

Population: All participants who were randomized and received any MEDI-528

Tmax of MEDI-528 in serum

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Time to Observed Maximum Serum Concentration (Tmax)	—	0.028 Day Geometric Coefficient of Variation 20.4

SECONDARY outcome

Timeframe: Days -21 to -7, 7, 28, and 56

Population: All participants who were randomized and received any MEDI-528

Tmax of MEDI-528 in sputum

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Time to Observed Maximum Sputum Concentration (Tmax)	—	9.276 Day Geometric Coefficient of Variation 99

SECONDARY outcome

Timeframe: Days -6 to -1, 8, 29, and 57

Population: All participants who were randomized and received any MEDI-528

Tmax of MEDI-528 in nasal lavage

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Time to Observed Maximum Nasal Lavage Concentration (Tmax)	—	10.319 Day Geometric Coefficient of Variation 169.6

SECONDARY outcome

Timeframe: Days 0, 6, 7, 27, 55, 84, and 126

Population: All participants who were randomized and received any MEDI-528

Cmax of MEDI-528 in serum

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Observed Maximum Serum Concentration (Cmax)	—	229.672 Microgram per milliliter Geometric Coefficient of Variation 18.1

SECONDARY outcome

Timeframe: Days -21 to -7, 7, 28, and 56

Population: All participants who were randomized and received any MEDI-528

Cmax of MEDI-528 in sputum

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Observed Maximum Sputum Concentration (Cmax)	—	71.843 Nanogram per milliliter Geometric Coefficient of Variation 78.7

SECONDARY outcome

Timeframe: Days -6 to -1, 8, 29, and 57

Population: All participants who were randomized and received any MEDI-528

Cmax of MEDI-528 in nasal lavage

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Observed Maximum Nasal Lavage Concentration (Cmax)	—	79.406 Nanogram per milliliter Geometric Coefficient of Variation 136.6

SECONDARY outcome

Timeframe: Days 0, 6, 7, 27, 55, 84, and 126

Population: All participants who were randomized and received any MEDI-528

AUC(0-t) of MEDI-528 in serum

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Area Under the Concentration Curve From Time Zero to Last Measurable Concentration [AUC(0-t)]	—	5744.821 Microgram times day per milliliter Geometric Coefficient of Variation 14.8

SECONDARY outcome

Timeframe: Days -21 to -7, 7, 28, and 56

Population: All participants who were randomized and received any MEDI-528

AUC(0-t) of MEDI-528 in sputum

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Area Under the Concentration Curve From Time Zero to Last Measurable Concentration [AUC(0-t)]	—	2382.123 Nanogram times day per milliliter Geometric Coefficient of Variation 84

SECONDARY outcome

Timeframe: Days -6 to -1, 8, 29, and 57

Population: All participants who were randomized and received any MEDI-528

AUC(0-t) of MEDI-528 in nasal lavage

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Area Under the Concentration Curve From Time Zero to Last Measurable Concentration [AUC(0-t)]	—	1332.408 Nanogram times day per milliliter Geometric Coefficient of Variation 147.6

SECONDARY outcome

Timeframe: Days 0, 6, 7, 27, 55, 84, and 126

Population: All participants who were randomized and received any MEDI-528

AUC(0-infinity) of MEDI-528 in serum

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Area Under the Concentration Curve From Time Zero to Infinity [AUC(0-infinity)]	—	6224.272 Microgram times day per milliliter Geometric Coefficient of Variation 17

SECONDARY outcome

Timeframe: Days -21 to -7, 7, 28, and 56

Population: All participants who were randomized, received any MEDI-528, and had sputum samples obtained

AUC(0-infinity) of MEDI-528 in sputum

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=10 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Area Under the Concentration Curve From Time Zero to Infinity [AUC(0-infinity)]	—	4136.234 Nanogram times day per milliliter Geometric Coefficient of Variation 61.9

SECONDARY outcome

Timeframe: Days -6 to -1, 8, 29, and 57

Population: All participants who were randomized, received any MEDI-528, and had nasal lavage samples obtained

AUC(0-infinity) of MEDI-528 in nasal lavage

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=10 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Area Under the Concentration Curve From Time Zero to Infinity [AUC(0-infinity)]	—	6047.098 Nanogram times day per milliliter Geometric Coefficient of Variation 134

SECONDARY outcome

Timeframe: Days 0, 6, 7, 27, 55, 84, and 126

Population: All participants who were randomized and received any MEDI-528

AUC(ext) of MEDI-528 in serum

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Percent of Total Area Under the Concentration Curve Extrapolated From Last Measurable Time to Infinity [AUC(Ext)]	—	6.441 Percent Geometric Coefficient of Variation 59.3

SECONDARY outcome

Timeframe: Days -21 to -7, 7, 28, and 56

Population: All participants who were randomized, received any MEDI-528, and had sputum samples obtained

AUC(ext) of MEDI-528 in sputum

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=10 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Percent of Total Area Under the Concentration Curve Extrapolated From Last Measurable Time to Infinity [AUC(Ext)]	—	25.919 Percent Geometric Coefficient of Variation 81.3

SECONDARY outcome

Timeframe: Days -6 to -1, 8, 29, and 57

Population: All participants who were randomized, received any MEDI-528, and had nasal lavage samples obtained

AUC(ext) of MEDI-528 in nasal lavage

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=10 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Percent of Total Area Under the Concentration Curve Extrapolated From Last Measurable Time to Infinity [AUC(Ext)]	—	18.848 Percent Geometric Coefficient of Variation 178.3

SECONDARY outcome

Timeframe: Days 0, 6, 7, 27, 55, 84, and 126

Population: All participants who were randomized and received any MEDI-528

T1/2 of MEDI-528 in serum

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Terminal Phase Half-Life (T1/2)	—	34.316 Day Geometric Coefficient of Variation 20.8

SECONDARY outcome

Timeframe: Days -21 to -7, 7, 28, and 56

Population: All participants who were randomized, received any MEDI-528, and had sputum samples obtained

T1/2 of MEDI-528 in sputum

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=10 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Terminal Phase Half-Life (T1/2)	—	31.933 Day Geometric Coefficient of Variation 83.1

SECONDARY outcome

Timeframe: Days -6 to -1, 8, 29, and 57

Population: All participants who were randomized, received any MEDI-528, and had nasal lavage samples obtained

T1/2 of MEDI-528 in nasal lavage

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=4 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Terminal Phase Half-Life (T1/2)	—	25.584 Day Geometric Coefficient of Variation 69

SECONDARY outcome

Timeframe: Days 0, 6, 7, 27, 55, 84, and 126

Population: All participants who were randomized and received any MEDI-528

CL of MEDI-528 in serum

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Total Body Clearance (CL)	—	0.101 Liter per day Geometric Coefficient of Variation 26.7

SECONDARY outcome

Timeframe: Days 0, 6, 7, 27, 55, 84, and 126

Population: All participants who were randomized and received any MEDI-528

Vz of MEDI-528 in serum

Outcome measures

Measure	PLACEBO Placebo administered as a single intravenous (IV) infusion	MEDI528 9 mg/kg n=15 Participants MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Terminal Phase Volume of Distribution (Vz)	—	5.025 Liter Geometric Coefficient of Variation 23.8

Adverse Events

PLACEBO

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

MEDI528 9 mg/kg

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	PLACEBO n=15 participants at risk	MEDI528 9 mg/kg n=15 participants at risk MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Nervous system disorders Epilepsy	6.7% 1/15 • Number of events 1	0.00% 0/15

Other adverse events

Measure	PLACEBO n=15 participants at risk	MEDI528 9 mg/kg n=15 participants at risk MEDI-528 at a single dose of 9 mg/kg administered as an IV infusion
Eye disorders Lacrimation increased	0.00% 0/15	6.7% 1/15 • Number of events 1
Eye disorders Vision blurred	0.00% 0/15	6.7% 1/15 • Number of events 1
Gastrointestinal disorders Diarrhoea	0.00% 0/15	6.7% 1/15 • Number of events 1
Gastrointestinal disorders Enteritis	0.00% 0/15	6.7% 1/15 • Number of events 1
Gastrointestinal disorders Gastritis	0.00% 0/15	6.7% 1/15 • Number of events 1
Gastrointestinal disorders Nausea	0.00% 0/15	13.3% 2/15 • Number of events 3
Gastrointestinal disorders Vomiting	0.00% 0/15	6.7% 1/15 • Number of events 1
General disorders Asthenia	0.00% 0/15	13.3% 2/15 • Number of events 2
General disorders Chills	6.7% 1/15 • Number of events 1	0.00% 0/15
General disorders Pyrexia	0.00% 0/15	6.7% 1/15 • Number of events 1
Infections and infestations Chlamydial infection	6.7% 1/15 • Number of events 1	0.00% 0/15
Infections and infestations Pharyngitis	6.7% 1/15 • Number of events 1	0.00% 0/15
Infections and infestations Nasopharyngitis	0.00% 0/15	13.3% 2/15 • Number of events 3
Infections and infestations Sinusitis	6.7% 1/15 • Number of events 1	0.00% 0/15
Infections and infestations Vaginal infection	6.7% 1/15 • Number of events 1	0.00% 0/15
Injury, poisoning and procedural complications Skin laceration	0.00% 0/15	6.7% 1/15 • Number of events 1
Investigations Alanine aminotransferase increased	6.7% 1/15 • Number of events 1	6.7% 1/15 • Number of events 1
Investigations Aspartate aminotransferase increased	0.00% 0/15	6.7% 1/15 • Number of events 1
Investigations Blood bicarbonate decreased	0.00% 0/15	6.7% 1/15 • Number of events 1
Investigations Blood potassium decreased	26.7% 4/15 • Number of events 6	26.7% 4/15 • Number of events 6
Investigations Haemoglobin decreased	0.00% 0/15	6.7% 1/15 • Number of events 3
Investigations Lymphocyte count decreased	20.0% 3/15 • Number of events 4	0.00% 0/15
Investigations Neutrophil count decreased	13.3% 2/15 • Number of events 3	0.00% 0/15
Investigations Protein urine present	6.7% 1/15 • Number of events 2	20.0% 3/15 • Number of events 3
Investigations White blood cell count decreased	20.0% 3/15 • Number of events 5	6.7% 1/15 • Number of events 1
Investigations White blood cell count increased	6.7% 1/15 • Number of events 1	0.00% 0/15
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/15	13.3% 2/15 • Number of events 2
Musculoskeletal and connective tissue disorders Bursitis	6.7% 1/15 • Number of events 1	0.00% 0/15
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/15	6.7% 1/15 • Number of events 1
Nervous system disorders Dizziness	0.00% 0/15	13.3% 2/15 • Number of events 2
Nervous system disorders Headache	6.7% 1/15 • Number of events 1	6.7% 1/15 • Number of events 1
Nervous system disorders Sciatica	6.7% 1/15 • Number of events 1	0.00% 0/15
Psychiatric disorders Anxiety	6.7% 1/15 • Number of events 1	0.00% 0/15
Respiratory, thoracic and mediastinal disorders Asthma	6.7% 1/15 • Number of events 2	0.00% 0/15
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.00% 0/15	6.7% 1/15 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	6.7% 1/15 • Number of events 1	0.00% 0/15
Skin and subcutaneous tissue disorders Erythema	0.00% 0/15	6.7% 1/15 • Number of events 1
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/15	6.7% 1/15 • Number of events 1

Additional Information

Don Raible, MD

MedImmune

Phone: 301-398-0000

Email: raibleD@medimmune.com

Results disclosure agreements

• Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.
• Publication restrictions are in place

Restriction type: OTHER