A Pharmacokinetics and Safety Study of Nemolizumab in Adolescent Participants With Atopic Dermatitis (AD)

NCT03921411 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: RD.06.SPR.116912
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study was to evaluate the pharmacokinetics and safety of nemolizumab in adolescent participants with AD.

Conditions

Atopic Dermatitis

Keywords

Nemolizumab; Atopic dermatitis

Outcome Measures

Primary Outcomes (34)

• Nemolizumab Serum Concentrations at Week 1-2

  Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).

  At week 1-2

• Nemolizumab Serum Concentrations at Week 4

  Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).

  At week 4

• Nemolizumab Serum Concentrations at Week 8

  Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).

  At week 8

• Nemolizumab Serum Concentrations at Week 12

  Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).

  At week 12

• Nemolizumab Serum Concentrations at Week 16

  Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).

  At week 16

• Nemolizumab Serum Concentrations at Week 24

  Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).

  At week 24

• Apparent Clearance After Extravascular Administration (Cl/F) of Nemolizumab

  CL/F is apparent clearance of the drug from the serum, calculated as the drug dose divided area under the curve from time 0 extrapolated to infinite time \[AUC (0-inf)\].

  Baseline to week 24

• Apparent Volume of Distribution After Extravascular Administration (Vd/F) of Nemolizumab

  Vd/F was calculated as dose divided by lambda\_z \*AUC(0-inf).

  Baseline to week 24

• Population Lag Time (Tlag)

  Lag time is defined as the time taken for a drug to appear in the systemic circulation following administration. The population Tlag value was estimated for the overall population and was reported in this endpoint.

  Baseline to week 24

• First Order Constant of Absorption (ka)

  PK of Nemolizumab was evaluated in participants using Ka using PK samples collected on Weeks 1-2, 4, 8, 12, 16 and 24. Ka was evaluated by population PK (popPK) methods and mean and standard from the model has been tabulated.

  Baseline to week 24

• Maximum Observed Serum Concentration (Cmax) of Nemolizumab

  Cmax was obtained from serum concentration time curve.

  Baseline to week 12

• Time to Reach Maximum Observed Serum Concentration (Tmax) of Nemolizumab

  Time to reach maximum observed serum concentration (Tmax) for Nemolizumab was derived from serum concentrations versus time data.

  Baseline to week 12

• Trough Serum Concentration (Ctrough) of Nemolizumab at Week 4

  Ctrough is the concentration prior to study drug administration.

  At week 4

• Trough Serum Concentration (Ctrough) of Nemolizumab at Week 8

  Ctrough is the concentration prior to study drug administration.

  At week 8

• Trough Serum Concentration (Ctrough) of Nemolizumab at Week 12

  Ctrough is the concentration prior to study drug administration.

  At week 12

• Trough Serum Concentration (Ctrough) of Nemolizumab at Week 16

  Ctrough is the concentration prior to study drug administration.

  At week 16

• Area Under the Serum Concentration-Time Curve From Zero to 4 Week Post-dose (AUC0-4w)

  Area under the drug concentration-time curve from 0 to 4 week post dosing for Nemolizumab. AUC(0-4w) was calculated according to the mixed log-linear trapezoidal rule.

  Pre-dose through 4 weeks post-dose

• Area Under the Serum Concentration-Time Curve From Time Zero to 8 Week Post-dose (AUC0-8w)

  Area under the drug concentration-time curve from 0 to 8 week post dosing for Nemolizumab. AUC(0-8w) was calculated according to the mixed log-linear trapezoidal rule.

  Pre-dose through 8 weeks post-dose

• Area Under the Serum Concentration-Time Curve From Time Zero to 12 Week Post-dose (AUC0-12w)

  Area under the drug concentration-time curve from 0 to 12 week post dosing for Nemolizumab. AUC(0-12w) was calculated according to the mixed log-linear trapezoidal rule.

  Pre-dose through 12 week post-dose

• Area Under the Serum Concentration-Time Curve From Time Zero to 16 Week Post-dose (AUC0-16w)

  Area under the drug concentration-time curve from 0 to 16 week post dosing for Nemolizumab. AUC(0-16w) was calculated according to the mixed log-linear trapezoidal rule.

  Pre-dose through 16 weeks post-dose

• Apparent Terminal Half-life (t1/2)

  Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the serum to decrease by 50%.

  Baseline to week 24

• Number of Participants With Treatment-Related Positive Anti-Drug Antibodies (ADA) in Serum at Week 4

  Antidrug antibodies were determined using a validated enzyme-linked immunosorbent assay (ELISA) assay. Number of participants with positive ADA in Serum were reported.

  At week 4

• Number of Participants With Neutralizing Antibodies

  The number of participants with neutralizing antibodies response at time of baseline up to week 24 has been presented. Neutralizing antibodies response assay result have been only presented for participants with positive anti-drug antibody assay.

  Baseline up to Week 24

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Adverse Event of Special Interests (AESI) and Serious Adverse Events (SAEs)

  An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAE was defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. An AESI is a noteworthy event for study drug that should be monitored closely and reported immediately. The following AEs will be considered AESIs: Anaphylactic reactions, Acute allergic reactions requiring treatment, Severe injection site reaction, Newly-diagnosed asthma or worsening of asthma, Peripheral edema: limbs, bilateral and Facial edema.

  Baseline through week 24

• Number of Participants With Asthma Control Test (ACT) Score Less Than or Equal to (=<) 19 at Week 1-2

  The ACT is a participant-completed assessment consisting of 5 questions health survey for measuring asthma control. Each question is answered with a score in a range of 1 to 5 and lower score represents the more severe condition. The scale range for Question 1 is "all the time" (1) to "none of the time" (5); Question 2 range: "more than once a day" (1) to "not at all" (5); Question 3 range: "4 or more nights a week" (1) to "not at all" (5); Question 4 range: "3 or more times per day" (1) to "not at all" (5); Question 5 range: "not controlled at all" (1) to "completely controlled" (5). A total ACT score is obtained as the sum of the 5 individual question scores that is from 5 to 25, where Higher scores mean that asthma is more controlled.

  At week 1-2

• Number of Participants With Asthma Control Test (ACT) Score Less Than or Equal to (=<) 19 at Week 4

  The ACT is a participant-completed assessment consisting of 5 questions health survey for measuring asthma control. Each question is answered with a score in a range of 1 to 5 and lower score represents the more severe condition. The scale range for Question 1 is "all the time" (1) to "none of the time" (5); Question 2 range: "more than once a day" (1) to "not at all" (5); Question 3 range: "4 or more nights a week" (1) to "not at all" (5); Question 4 range: "3 or more times per day" (1) to "not at all" (5); Question 5 range: "not controlled at all" (1) to "completely controlled" (5). A total ACT score is obtained as the sum of the 5 individual question scores that is from 5 to 25, where Higher scores mean that asthma is more controlled.

  At week 4

• Number of Participants With Asthma Control Test (ACT) Score Less Than or Equal to (=<) 19 at Week 8

  The ACT is a participant-completed assessment consisting of 5 questions health survey for measuring asthma control. Each question is answered with a score in a range of 1 to 5 and lower score represents the more severe condition. The scale range for Question 1 is "all the time" (1) to "none of the time" (5); Question 2 range: "more than once a day" (1) to "not at all" (5); Question 3 range: "4 or more nights a week" (1) to "not at all" (5); Question 4 range: "3 or more times per day" (1) to "not at all" (5); Question 5 range: "not controlled at all" (1) to "completely controlled" (5). A total ACT score is obtained as the sum of the 5 individual question scores that is from 5 to 25, where Higher scores mean that asthma is more controlled.

  At week 8

• Number of Participants With Asthma Control Test (ACT) Score Less Than or Equal to (=<) 19 at Week 12

  The ACT is a participant-completed assessment consisting of 5 questions health survey for measuring asthma control. Each question is answered with a score in a range of 1 to 5 and lower score represents the more severe condition. The scale range for Question 1 is "all the time" (1) to "none of the time" (5); Question 2 range: "more than once a day" (1) to "not at all" (5); Question 3 range: "4 or more nights a week" (1) to "not at all" (5); Question 4 range: "3 or more times per day" (1) to "not at all" (5); Question 5 range: "not controlled at all" (1) to "completely controlled" (5). A total ACT score is obtained as the sum of the 5 individual question scores that is from 5 to 25, where Higher scores mean that asthma is more controlled.

  At week 12

• Number of Participants With Clinically Significant Abnormalities in Physical Examination (PE) Findings

  A complete PE included assessments of the head, ears, eyes, nose, throat, neck (including thyroid), skin/integumentary system, cardiovascular system, respiratory system, gastrointestinal system, musculoskeletal system, lymph nodes, and nervous system. Clinical significance was determined by the investigator.

  Baseline up to Week 24

• Number of Participants With Clinically Significant Abnormalities in Laboratory Values

  Laboratory investigation included hematology, biochemistry, and urinalysis. Clinical significance was determined by the investigator. The number of participants with clinically significant abnormalities in laboratory parameters were reported.

  Baseline up to Week 24

• Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings at Week 16

  The ECG recordings were obtained after 10 minutes of rest in a semi-supine position. Number of participants with clinically significant change from baseline in ECG findings were reported. Clinically significance was decided by investigator.

  At week 16

• Number of Participants With Clinically Significant Abnormalities in Vital Signs

  Vital signs included pulse rate, systolic and diastolic blood pressure (after the participant had been sitting for at least 5 minutes), and body temperature. Clinically significance was decided by investigator..

  Baseline up to Week 24

• Number of Participants With Abnormal Peak Expiratory Flow (PEF) <80% of Predicted Value at Week 1-2

  PEF was the maximum speed of expiration measured using spirometer. A participant took rest just before the measurement. At each time of measurement, a participant expired for at least 6 seconds wherever possible. At each time of measurement, at least 3 readings were obtained, and three readings which were obtained in an appropriate manner were stored. PEF \<80% of predictive value is considered as abnormal.

  At week 1-2

• Number of Participants With Abnormal Peak Expiratory Flow (PEF) <80% Predicted Value at Week 4

  PEF was the maximum speed of expiration measured using spirometer. A participant took rest just before the measurement. At each time of measurement, a participant expired for at least 6 seconds wherever possible. At each time of measurement, at least 3 readings were obtained, and three readings which were obtained in an appropriate manner were stored. PEF \<80% of predictive value is considered as abnormal.

  At week 4

Secondary Outcomes (18)

• Non-Compartmental Analysis: Area Under the Serum Concentration-time Curve From Time Zero to 4 Weeks Post-dose AUC(0-4w)

  Pre-dose through 4 weeks post-dose

• Non-Compartmental Analysis: Area Under the Serum Concentration-Time Curve From Time Zero to 8 Week Post-dose (AUC0-8w)

  Pre-dose through 8 weeks post-dose

• Non-Compartmental Analysis: Area Under the Serum Concentration-Time Curve From Time Zero to 12 Week Post-dose (AUC0-12w)

  Pre-dose through 12 week post-dose

• Non-Compartmental Analysis: Area Under the Serum Concentration-Time Curve From Time Zero to 16 Week Post-dose (AUC0-16w)

  Pre-dose through 16 weeks post-dose

• Absolute Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16

  Baseline, Week 16

Study Arms (1)

Nemolizumab

EXPERIMENTAL

Nemolizumab

Biological: Nemolizumab

Interventions

Nemolizumab BIOLOGICAL

Participants received subcutaneous (SC) injection of 30 milligram (mg) of Nemolizumab every 4 weeks (Q4W) over a 16-week treatment period, with a loading dose of 60 mg on Day 1.

Nemolizumab

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female participants ≥ 12 to \< 17 years of age
• Chronic AD that has been documented for at least 2 years
• Eczema Area and Severity Index (EASI) score ≥ 16
• Investigator's Global Assessment (IGA) score ≥ 3
• AD involvement ≥ 10% of Body Surface Area (BSA)
• Documented recent history of inadequate response to topical medications
• Women of childbearing potential must agree to be strictly abstinent or to use an effective and approved method of contraception throughout the study and for 12 weeks after the last study drug injection.

You may not qualify if:

• Body weight \< 30 kilogram (kg)
• Cutaneous infection within 1 week or any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics, or antifungals within 1 week
• History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, example., monoclonal antibody)
• Any medical or psychological condition, or any clinically relevant laboratory abnormalities that may have put the subject at significant risk according to the investigator's judgment

Sponsors & Collaborators

• Galderma R&D: lead

Study Sites (10)

Galderma Investigational Site

Fountain Valley, California, 92708, United States

Location

Galderma Investigational Site

Fremont, California, 94538, United States

Location

Galderma Investigational Site

Jacksonville, Florida, 32256, United States

Location

Galderma Investigational Site

Tampa, Florida, 33607, United States

Location

Galderma Investigational Site

Columbus, Georgia, 31904, United States

Location

Galderma Investigational Site

Sandy Springs, Georgia, 30128, United States

Location

Galderma Investigational Site

Gresham, Oregon, 97030, United States

Location

Galderma Investigational Site

Dallas, Texas, 75230-5806, United States

Location

Galderma Investigational Site

Frisco, Texas, 75034, United States

Location

Galderma Investigational Site

Richmond, Virginia, 23220, United States

Location

Related Publications (1)

• Sidbury R, Alpizar S, Laquer V, Dhawan S, Abramovits W, Loprete L, Krishnaswamy JK, Ahmad F, Jabbar-Lopez Z, Piketty C. Pharmacokinetics, Safety, Efficacy, and Biomarker Profiles During Nemolizumab Treatment of Atopic Dermatitis in Adolescents. Dermatol Ther (Heidelb). 2022 Mar;12(3):631-642. doi: 10.1007/s13555-021-00678-7. Epub 2022 Jan 28.

  PMID: 35088348 DERIVED

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

nemolizumab

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Clinical Operations
• Organization: Galderma

Clinical.Studies@galderma.com

817 961 5000

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2019
• First Posted: April 19, 2019
• Study Start: April 9, 2019
• Primary Completion: August 19, 2020
• Study Completion: August 19, 2020
• Last Updated: April 21, 2023
• Results First Posted: April 21, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)