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Tralokinumab

Phase 3

Asthma | Monoclonal antibody | Respiratory |AstraZeneca PLC|Last Updated: Mar 15, 2019

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindACTIVE_CONTROLLEDDMCBiomarker
Total Trials5
Total Enrollment998
FDA Designations
No designations recorded
Clinical Trials (5)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02281357Phase 3 Study to Evaluate the Efficacy & Safety of Tralokinumab in Adults & Adolescents With OCS Dependent AsthmaPHASE3 COMPLETED 140Feb 19, 2015Sep 7, 2017Mar 15, 201951 United States, Belgium +5
NCT02449473Study to Evaluate Efficacy & Safety of Tralokinumab in Subjects With Asthma Inadequately Controlled on CorticosteroidsPHASE2 COMPLETED 79Sep 29, 2015Jun 21, 2017Jan 8, 201915 Canada, Denmark +1
NCT01402986A Safety and Efficacy Study of Tralokinumab in Adults With AsthmaPHASE2 COMPLETED 689Aug 1, 2011Feb 1, 2014Apr 4, 201789 United States, Argentina +13
NCT02085473A Study of Tralokinumab When Delivered Subcutaneously at Different Flow Rates to Healthy VolunteersPHASE1 COMPLETED 60Mar 19, 2014Jul 10, 2014Dec 31, 20182 United States
NCT01592396A Phase 1, Open-label Study to Investigate the Pharmacokinetics of Tralokinumab (CAT-354) in Adolescents With AsthmaPHASE1 COMPLETED 30Jun 1, 2012Jan 1, 2013Mar 6, 20173 Poland
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Study Endpoints
Primary Endpoints
Percent Change From Baseline in the Final Daily, Average, OCS Dose at Week 40 While Not Losing Asthma Control.
Baseline (Week 0) and Week 40

The 40-week treatment period consisted of 3 phases: an induction phase (Week 0 to Week 12) where patients remained on their optimised OCS dose; an OCS reduction phase (Week 12 to Week 32) where OCS dose reduction could have started at Week 12 with the possibility of dose titration every 4 weeks to reach the lowest possible OCS dose; and a maintenance phase (Week 32 to Week 40) where patients remained on the OCS dose reached at Week 32 to demonstrate asthma control was maintained after achieving the lowest OCS dose. Criteria used to assess asthma control included lung function assessments (forced expiratory volume in 1 second and morning peak expiratory flow), night awakenings, and the use of rescue medication and systemic corticosteroids. The least squares (LS) mean percent change from baseline in average daily OCS dose is presented. The final daily percent change from baseline was defined as {(Final daily average dose - baseline daily average dose)/baseline daily average dose}\*100%.

Change From Baseline to Week 12, Expressed as a Ratio, in Number of Airway Submucosal Eosinophils
Baseline (Week 0) and Week 12

The number of airway submucosal eosinophils per millimetre squared (mm\^2) was determined by microscopic evaluation of bronchoscopic biopsies. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of airway submucosal eosinophils is presented as geometric mean ± standard deviation (SD) of log values.

Annual Asthma Exacerbation Rate (AER)
Week 1 up to Week 53

Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed or administered by the investigator or healthcare provider; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. An asthma exacerbation event was considered resolved 7 days after the last dose of oral corticosteroids (OCS) is administered (10 days after administration of an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.

Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity])
Day 1 (pre-dose sample collected within 30 minutes prior to study drug administration), Days 2, 4, 6, 8, 10, 15, 22, 36, and 57 post-dose

AUC (0 - infinity) = Area under the serum concentration versus time curve (AUC) from time zero to infinite time, obtained from AUC (0 - t) plus AUC (t - infinity). Units are day\*micrograms per millilitres = day\*mcg/mL.

Maximum Observed Serum Concentration (Cmax)
Day 1 (pre-dose sample collected within 30 minutes prior to study drug administration), Days 2, 4, 6, 8, 10, 15, 22, 36, and 57 post-dose

The Cmax is the maximum observed serum concentration of tralokinumab.

Time to Maximum Concentration (Tmax)
Day 1 (pre-dose sample collected within 30 minutes prior to study drug administration), Days 2, 4, 6, 8, 10, 15, 22, 36, and 57 post-dose

Tmax is defined as actual sampling time to reach maximum observed tralokinumab concentration.

Area Under the Concentration-Time Curve From Zero to Last Measurable Concentration (AUC [0-t])
Day 1 (pre-dose sample collected within 30 minutes prior to study drug administration), Days 2, 4, 6, 8, 10, 15, 22, 36, and 57 post-dose

AUC \[0-t\] is defined as area under the serum concentration-time curve from zero to last observed tralokinumab concentration.

Terminal Elimination Half-life (t1/2)
Day 1 (pre-dose sample collected within 30 minutes prior to study drug administration), Days 2, 4, 6, 8, 10, 15, 22, 36, and 57 post-dose

Terminal elimination half-life is the time measured for the serum concentration to decrease by one half. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).

Apparent Systemic Clearance (CL/F) After Subcutaneous Dose
Day 1 (pre-dose sample collected within 30 minutes prior to study drug administration), Days 2, 4, 6, 8, 10, 15, 22, 36, and 57 post-dose

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after subcutaneous dose (apparent systemic clearance) is influenced by the fraction of the dose absorbed (bioavailability).

Apparent Terminal-Phase Volume of Distribution (Vz/F)
Day 1 (pre-dose sample collected within 30 minutes prior to study drug administration), Days 2, 4, 6, 8, 10, 15, 22, 36, and 57 post-dose

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.

Time to Reach Maximum Observed Serum Concentration (Tmax)
0 (predose), 3, 8 and 24 hours postdose on Day 1; Day 4, 6, 8, 10, 15, 22, 36 and 57
Terminal Phase Elimination Half Life (t1/2)
0 (predose), 3, 8 and 24 hours postdose on Day 1; Day 4, 6, 8, 10, 15, 22, 36 and 57

Terminal phase elimination half-life is the time measured for the serum concentration to decrease by one half.

Secondary Endpoints
The Number of Patients With Final Daily Average OCS Dose ≤5 mg at Week 40.
At Week 40
The Number of Patients With ≥50% Reduction in Final Average Daily OCS Dose at Week 40.
At Week 40
Annual Asthma Exacerbation Rate (AAER) up to Week 40.
Baseline (Week 0) up to Week 40
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Study Design & Arms
AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
TralokinumabEXPERIMENTALTralokinumab subcutaneous injection
PlaceboPLACEBO_COMPARATORPlacebo subcutaneous injection
Tralokinumab Dose RegimenEXPERIMENTALTralokinumab Subcutaneous Injection
Placebo Dose RegimenPLACEBO_COMPARATORPlacebo Subcutaneous Injection
Placebo, Q2W - Cohort 1PLACEBO_COMPARATORParticipants received matching placebo subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.
Tralokinumab 300 mg, Q2W - Cohort 1EXPERIMENTALParticipants received tralokinumab 300 milligram (mg) subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.
Placebo, Q2/4W - Cohort 2PLACEBO_COMPARATORParticipants received matching placebo subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for 38 weeks (Q2/4W) for a total of 16 doses.
Tralokinumab 300 mg, Q2/4W - Cohort 2EXPERIMENTALParticipants received tralokinumab 300 mg subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for 38 weeks (Q2/4W) for a total of 16 doses.
Cohort 1ACTIVE_COMPARATORParticipants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 'W' mL/min.
Cohort 2EXPERIMENTALParticipants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 'X' mL/min.
Cohort 3EXPERIMENTALParticipants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 'Y' mL/min.
Cohort 4EXPERIMENTALParticipants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 'Z' mL/min.
Tralokinumab 300 mgEXPERIMENTALParticipants aged 12 to 14 years and 15 to 17 years will receive a single dose of tralokinumab (CAT-354) 300 milligram (mg), subcutaneously on Day 1.
Interventions
NameTypeDescription
TralokinumabBIOLOGICALTralokinumab dose
PlaceboOTHERPlacebo dose
Placebo Q2WOTHERParticipants who received matching placebo subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.
Tralokinumab 300 mg, Q2WBIOLOGICALParticipants received tralokinumab 300 mg subcutaneous injection Q2W for a total of 26 doses up to 50 weeks.
Placebo, Q2/4WOTHERParticipants received matching placebo subcutaneous injection Q2W for 12 weeks followed by Q4W for 38 weeks (Q2/4W) for a total of 16 doses.
Tralokinumab 300 mg, Q2/4WBIOLOGICALParticipants received tralokinumab 300 mg subcutaneous injection Q2W for 12 weeks followed by Q4W for 38 weeks (Q2/4W) for a total of 16 doses.
Tralokinumab 300 mgBIOLOGICALParticipants will receive 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at different flow rates.
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Eligibility Criteria
Age Range12 Years — 75 Years
SexALL
Healthy VolunteersNo
Study Sites51

Inclusion Criteria: 1\) Age 12-75 2) Documented physician-diagnosed asthma. 3) Documented treatment with ICS at a total daily dose corresponding to ≥500µg fluticasone propionate dry powder formulation and a LABA. 4) Subjects must have received OCS for the treatment of asthma for 6 months prior to V...

Countries:United StatesBelgiumFranceGermanyNetherlandsPolandUkraineCanadaDenmarkUnited KingdomArgentinaChileCzechiaJapanMexicoPhilippinesRussiaSouth KoreaSpain
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