A Study to Evaluate the Safety and Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Melrilimab (GSK3772847) in Healthy Participants

NCT04366349 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 209635
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

GSK3772847, an anti-interleukin (IL) 33-receptor monoclonal antibody, is a novel treatment for asthma. The purpose of this study to evaluate the safety and tolerability, PK and PD of single ascending doses of GSK3772847 administered subcutaneously (SC) to healthy participants. This study will also establish the bioavailability of SC formulation and evaluate the safety in particular injection site tolerability of route. Participants will either receive a single dose of 70 milligram (mg) GSK3772847 or placebo in (Cohort 1) and 140 mg GSK3772847 or placebo in Cohorts 2, 3 (Japanese participants) and 4 (Chinese participants). The site of injection will be upper arm; abdomen or thigh for cohorts 1 and 2 with cohorts 3 and 4 will receive injections in the upper arm only. Approximately, the total duration of study will be up to 89 days.

Conditions

Healthy Volunteers; Asthma

Keywords

Pharmacokinetics; Pharmacodynamics; Safety; GSK3772847; Tolerability

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and other situations which involve medical or scientific judgment.

  Up to Day 85

• Area Under the Plasma Concentration Time Curve From 0 to t (AUC[0-t]) of GSK3772847

  Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847. Pharmacokinetic Population consisted of all randomized participants who received at least one dose of study treatment, and for whom at least one pharmacokinetic sample was obtained, analyzed and measurable.

  Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85

• Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) of GSK3772847

  Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847.

  Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85

• Maximum Observed Plasma Concentration (Cmax) of GSK3772847

  Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847.

  Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85

• Time to Cmax (Tmax) of GSK3772847

  Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847.

  Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85

• Apparent Terminal Half-life (t1/2) of GSK3772847

  Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847.

  Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85

Secondary Outcomes (4)

• Maximal Decrease in Ratio to Baseline in Free Soluble Suppressor of Tumorigenicity 2 (ST2) Concentration

  Baseline and up to Day 85/early withdrawal

• Maximal Increase in Ratio to Baseline in Total Soluble ST2 Concentration

  Baseline and up to Day 85/early withdrawal

• Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies

  Days 1, 15, 29, 57 and 85/early withdrawal

• Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol

  Baseline, Days 5, 15, 29 and 85/early withdrawal

Study Arms (3)

Participants receiving melrilimab (GSK3772847) 70 milligram (mg)

EXPERIMENTAL

Participants will receive a single dose of melrilimab (GSK3772847) 70 milligram (mg) subcutaneously (SC) injection by an health care professional (HCP).

Biological: melrilimab (GSK3772847) 70 milligram (mg)

Participants receiving melrilimab (GSK3772847) 140 milligram (mg)

EXPERIMENTAL

Participants will receive a single dose of melrilimab (GSK3772847) 140 milligram (mg) subcutaneously (SC) injection by an health care professional (HCP).

Biological: melrilimab (GSK3772847) 140 milligram (mg)

Participants receiving Placebo

PLACEBO COMPARATOR

Participants will receive a single dose of placebo subcutaneously (SC) injection by an health care professional (HCP).

Other: Placebo

Interventions

melrilimab (GSK3772847) 70 milligram (mg) BIOLOGICAL

melrilimab (GSK3772837) will be available at a dose strength of 70 milligram per milliliter (mg/mL) in a 3 milliliter (mL) glass vial.

Participants receiving melrilimab (GSK3772847) 70 milligram (mg)

melrilimab (GSK3772847) 140 milligram (mg) BIOLOGICAL

Two doses of melrilimab (GSK3772837) 70 milligram per milliliter (mg/mL) will be administered to achieve a dose strength of 140 milligram per milliliter (mg/mL)

Participants receiving melrilimab (GSK3772847) 140 milligram (mg)

Placebo OTHER

Placebo to match melrilimab (GSK3772847) will be available in the form of solution for injection in a 3 milliliter (mL) glass vial.

Participants receiving Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants age in between 18 to 65 years, at the time of signing the informed consent.

You may not qualify if:

• Japanese participants are eligible based on meeting all of the following criteria: healthy male and female participants born in Japan; are descendants of four ethnic Japanese grandparents and two ethnic Japanese parents; holding a Japanese passport or identity papers; being able to speak Japanese; have lived outside Japan for less than 10 years at the time of screening.
• Chinese Participants are eligible based on meeting all of the following: healthy male and female participants born in mainland China; are descendants of four Chinese grandparents and two Chinese parents; holding a Chinese passport or identity papers; being able to speak Chinese; have lived outside China for less than 10 years at the time of screening; Body weight 35-150 kilogram (kg) and body mass index (BMI) within the range 18-32 kilogram per square meter (kg/m2) (inclusive).
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Alanine transaminase (ALT) \>2 times of (x) upper limit of normal (ULN).
• Bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent \[%\]).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Ongoing or recurrent infections.
• QT interval corrected for heart rate by Fridericia's formula (QTcF) \>450 millisecond (msec) or any of the following abnormal and clinically significant electrocardiogram (ECG) findings; sinus bradycardia \<45 beats per minute (bpm); sinus tachycardia \>=110 bpm; multifocal atrial tachycardia (wandering atrial pacemaker with rate \>100 bpm); evidence of Mobitz II second degree or third degree atrioventricular (AV) block; pathological Q waves (defined as wide \[\>0.04 seconds\] and deep \[\>0.4 millivolt (mV) (4 millimeter (mm) with 10mm/mV setting)\] or \>25% of the height of the corresponding R wave, providing the R wave was \>0.5 mV \[5 mm with 10mm/mV setting\], appearing in at least two contiguous leads; Evidence of ventricular ectopic couplets, bigeminy, trigeminy or multifocal premature ventricular complexes; For participants without complete right bundle branch block: QT interval corrected for heart rate by Fridericia's formula (QTc\[F\]) \>=450 msec or an ECG that is unsuitable for QT measurements (e.g., poor defined termination of the T wave); for participants with complete right bundle branch block: QTc(F) \>=480 msec or an ECG that is unsuitable for QT measurements (e.g., poor defined termination of the T wave); ST-T wave abnormalities (excluding non-specific ST-T wave abnormalities); Clinically significant conduction abnormalities (e.g., Wolff-Parkinson-White syndrome or bifascicular block defined as complete left bundle branch block or complete right bundle branch block with concomitant left fascicular block); Clinically significant arrhythmias (e.g., atrial fibrillation with rapid ventricular response, ventricular tachycardia).
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including saint \[St\] John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the first dose of study medication and until study completion, unless in the opinion of the investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise participant safety.
• The participant has been in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention.
• Positive Hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
• Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Anaheim, California, 92801, United States

Location

Related Publications (1)

• Pefani E, Stone S, Zhu CQ, Nunn C, Fairman D. Safety, tolerability, and pharmacokinetics of a single ascending subcutaneous dose of GSK3772847 in healthy participants. Pharmacol Res Perspect. 2023 Apr;11(2):e01054. doi: 10.1002/prp2.1054.

  PMID: 36846967 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

melrilimab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double blind study and participants and investigator will be masked.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single arm study.

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: April 28, 2020
• Study Start: July 21, 2020
• Primary Completion: December 21, 2020
• Study Completion: December 21, 2020
• Last Updated: November 5, 2021
• Results First Posted: November 5, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (1)