A Study of Tralokinumab When Delivered Subcutaneously at Different Flow Rates to Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT02085473
• Recruitment Status: Completed
• First Posted: March 12, 2014
• Results First Posted: November 23, 2018
• Last Update Posted: December 31, 2018
• Sponsor: MedImmune LLC
• Information provided by (Responsible Party): MedImmune LLC

Study Description

Brief Summary:

The primary objective of this study is to evaluate the pharmacokinetics (PK) and tolerability of tralokinumab when delivered subcutaneously at different flow rates to healthy volunteers.

Condition or disease	Intervention/treatment	Phase
Asthma; Healthy Subjects or Volunteers	Biological: Tralokinumab 300 mg	Phase 1

Detailed Description:

This is a Phase 1, open-label, assessor-blind, parallel-group study to evaluate the PK and tolerability of a single subcutaneous dose of 300 milligram (mg) tralokinumab when delivered as a 2 milliliters (mL) injection at different flow rates to healthy adult volunteers.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase 1 Study to Evaluate the Pharmacokinetics and Tolerability of a Single Subcutaneous Dose of Tralokinumab When Delivered as a 2 mL Injection at Different Flow Rates to Healthy Volunteers
• Actual Study Start Date: March 19, 2014
• Actual Primary Completion Date: July 10, 2014
• Actual Study Completion Date: July 10, 2014

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Cohort 1; Participants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 'W' mL/min.	Biological: Tralokinumab 300 mg; Participants will receive 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at different flow rates.; Other Name: CAT-354
Experimental: Cohort 2; Participants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 'X' mL/min.	Biological: Tralokinumab 300 mg; Participants will receive 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at different flow rates.; Other Name: CAT-354
Experimental: Cohort 3; Participants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 'Y' mL/min.	Biological: Tralokinumab 300 mg; Participants will receive 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at different flow rates.; Other Name: CAT-354
Experimental: Cohort 4; Participants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 'Z' mL/min.	Biological: Tralokinumab 300 mg; Participants will receive 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at different flow rates.; Other Name: CAT-354

Outcome Measures

Primary Outcome Measures :

1. Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) [ Time Frame: 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.
2. Maximum Observed Serum Concentration (Cmax) [ Time Frame: 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.
3. Time to Maximum Concentration (Tmax) [ Time Frame: 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.
4. Area Under the Concentration-Time Curve From Zero to Last Measurable Concentration (AUC [0-t]) [ Time Frame: 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.
5. Terminal Elimination Half-life (t1/2) [ Time Frame: 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).
6. Apparent Systemic Clearance (CL/F) After Subcutaneous Dose [ Time Frame: 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).
7. Apparent Terminal-Phase Volume of Distribution (Vz/F) [ Time Frame: 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.

Secondary Outcome Measures :

1. Local Injection-Site Pain and Injection-Site Pruritus [ Time Frame: During the injection until 72 hours post-injection for injection site-pain and immediately after administration of injection until 72 hours for injection-site pruritus ]
   Local injection-site pain and pruritus intensity was rated on 0 to 100 millimeter (mm) visual analogue scale (VAS) at various time points, where 0 = no pain/ no pruritus; 100 = most severe pain/ most severe pruritus. Injection site pruritus intensity was assessed by the blinded assessor. Higher the score indicated higher intensity of pain and pruritus. Local injection site pain and pruritus was assessed at below time-points: 1 and 6 minute (min) during investigational product administration (IPA); immediately post IPA, 10, 20, 30, and 60 min, 2, 4, 8, 24 and 72 hour (h) post IPA.
2. Number of Participants Reporting Local Injection-Site Reactions [ Time Frame: 0, 10, 20, 30 and 60 minutes, 2, 4, 8, 24 and 72 hours post-injection ]
   The signs and/or symptoms of local injection-site reactions including erythema, hematoma or bleeding, local warmth, swelling, and/or rash occurring within 72 hours post-injection were assessed and recorded by a blinded assessor.
3. Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: From start of study drug administration up to Day 57 ]
   An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly and important medical event. Treatment-emergent were events between administration of study drug and up to Day 57 that were absent before treatment or that worsened relative to pre-treatment state.
4. Number of Participants Reporting Treatment-emergent Adverse Events Related to Physical Examination [ Time Frame: Day 1 to Day 57 ]
   The treatment-emergent adverse events related to physical examination were reported as per investigator discretion. Treatment-emergent were the events between administration of study drug and up to Day 57 that were absent before treatment or that worsened relative to pre-treatment state.
5. Number of Participants Reporting Treatment-emergent Adverse Events Related to Vital Signs [ Time Frame: Day 1 to Day 57 ]
   Vital signs included systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate and temperature. The treatment-emergent adverse events related to vital signs were reported as per investigator discretion. Treatment-emergent were the events between administration of study drug and up to Day 57 that were absent before treatment or that worsened relative to pre-treatment state.
6. Number of Participants Reporting Treatment-emergent Adverse Events in Laboratory Parameters [ Time Frame: Day 1 to Day 57 ]
   Laboratory parameters included hematology, serum chemistry and urinalysis. The treatment-emergent adverse events in laboratory parameters were reported as per investigator discretion. Treatment-emergent were the events between administration of study drug and up to Day 57 that were absent before treatment or that worsened relative to pre-treatment state.
7. Number of Participants Exhibiting Anti-Drug Antibodies for Tralokinumab at Any Visit [ Time Frame: Pre-dose on Day 1 and Day 57 ]
   Immunogenicity assessment included determination of anti-drug antibodies to tralokinumab (CAT-354) antibodies in serum samples.

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Key Inclusion Criteria:

• Healthy males and females ages 19-65 years
• Body mass index of 19.0-30.0 kilogram per meter square (kg/m^2)
• No clinically significant abnormality
• Vital signs, electrocardiogram (ECG), and laboratory parameters within normal range
• Negative alcohol and drug screens
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use highly effective contraception
• Nonsterilized males who are sexually active with a female partner of childbearing potential must use highly effective contraception.

Key Exclusion Criteria:

• Concurrent enrollment in another clinical study where the subject is receiving an investigational product
• Receipt of any marketed or investigational biologic agent within 4 months or 5 half-lives prior to screening, whichever is longer
• Receipt of any investigational nonbiologic agent within 3 months or 5 half-lives prior to screening, whichever is longer
• Current use of regular pain-modifying, anti-depressant, anxiolytic, or hypnotic medication
• History of thrombocytopenia or bleeding disorder or use of anticoagulants
• History of any immunodeficiency disorder or use of immunosuppressive medication.
• History of a clinically significant infection
• History of cancer
• Positive Hepatitis B or C
• Positive HIV

Contacts and Locations

Locations

United States, Nebraska

Celerion

Lincoln, Nebraska, United States, 68502

Research Site

Lincoln, Nebraska, United States, 68502

Sponsors and Collaborators

MedImmune LLC

Investigators

• Principal Investigator: Barbara Cook, MD; Celerion

More Information

Additional Information:

Redacted Protocol 

Publications:

Jain M, Doughty D, Clawson C, Li X, White N, Agoram B, van der Merwe R. Tralokinumab pharmacokinetics and tolerability when administered by different subcutaneous injection methods and rates . Int J Clin Pharmacol Ther. 2017 Jul;55(7):606-620. doi: 10.5414/CP203023.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT02085473
• Other Study ID Numbers: D2210C00011
• First Posted: March 12, 2014
• Results First Posted: November 23, 2018
• Last Update Posted: December 31, 2018
• Last Verified: December 2018

Keywords provided by MedImmune LLC:

Asthma; Healthy Subjects or Volunteers; Tralokinumab; CAT-354

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases