Healthy Volunteers
Conditions
Keywords
Auto-Injector (AI), Dual-Chamber Syringe (DCS), Atopic dermatitis (AD), Prurigo nodularis (PN)
Brief summary
This study was to compare the rate and extent of absorption of a single dose of nemolizumab administered with auto-injectors \[AI\] (test) versus dual-chamber syringes \[DCS\] (reference) under controlled conditions in healthy adult subjects.
Interventions
DRUGNemolizumab
Nemolizumab with Auto-Injector (AI).
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male and female participants aged 18 to 65 years at screening visit. * Body weight \>= 45 kilogram (kg) and body mass index between \>=18.0 and \<30.0 kilograms per meter squared (kg/m\^2) at both screening and baseline visits. * Medically healthy with normal clinical status as judged by the investigator based on medical history, physical examination, and clinical laboratory tests. * Willing to abstain from all prescription medications during the study, (defined hereafter as after signing of informed consent form), except to treat AEs and contraception, and as permitted under Exclusion 2. Limited use of non-prescription medications/supplements that were not believed to affect participant's safety or the overall results of the study might be permitted at the discretion of investigator. * Female participants of childbearing potential (i.e., fertile, after menarche and, until becoming postmenopausal unless permanently sterile) must agree either to be strictly abstinent throughout the study and for 12 weeks after the study drug injection, or to use an adequate and approved method of contraception throughout the study and for 12 weeks after the study drug injection. Males are not required to use contraception, and there is no restriction on sperm donation. * Female participants of non-childbearing potential must meet one of these criteria; absence of menstrual bleeding for 1 year before the screening visit with no other medical reason, confirmed with follicle-stimulating hormone (FSH) level in the postmenopausal range or documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 3 months before the study. * Willing and able to comply with all of the time commitments and procedural requirements of the clinical study protocol. * Understood and signed an informed consent form before any investigational procedure(s) are performed.
Exclusion criteria
* History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, e.g., monoclonal antibody) or to any of the study drug excipients. * Cutaneous infection within 1 week before the baseline visit or any infection requiring treatment with oral, parental antibodies, antivirals, antiparasitics, or antifungals within 2 weeks before the baseline visit. * Any confirmed or suspected coronavirus disease (COVID-19) infection within 2 weeks before screening or baseline visit. * Positive serology results (hepatitis B surface antigen \[HBsAg\] or hepatitis B core antibody \[HBcAb\], hepatitis C \[HCV\] antibody with positive HCV RNA, or human immunodeficiency virus \[HIV\] antibody) at the screening visit. * Known or suspected immunosuppression or unusually frequent, recurrent, severe, or prolonged infections as per investigator judgment. * History of lymphoproliferative disease or history of malignancy of any organ system within last 5 years, except for basal cell carcinoma, squamous cell carcinoma in situ (Bowen's disease), or carcinomas in situ of the cervix that have been treated and have no clinical evidence of recurrence in the last 12 weeks before baseline visit, or actinic keratoses that have been treated. * Previous treatment with Nemolizumab. * Known active or untreated latent tuberculosis infection. * Any condition that may interfere with study assessments (e.g., poor venous access or needle phobia). * Having received a live-attenuated or non-live vaccine within 4 weeks before the baseline visit or are expected to be vaccinated during the study or during the 12 weeks after the last study drug injection, except for non-live seasonal vaccinations, COVID-19 and /or emergency vaccinations. * Planned or expected major surgical procedure during the clinical study. * Pregnant women, breastfeeding women, or women planning a pregnancy during the study or 12 weeks after the study drug injection. * Participating or participated in any other study with an investigational drug or device within the past 8 weeks before the screening visit, or is in an exclusion period from a previous study. * Participants who have donated ≥ 500 mL of blood in the last 3 months before doing. * History of alcohol or substance abuse within 6 months of the screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Nemolizumab | Pre-dose, 12 hours, 24 hours, Days 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 22, 29, 36, 43, 50, 57, 71, and 85 post-dose | Cmax was defined as the observed maximum serum concentration of nemolizumab. Cmax was used to measure the rate of absorption of nemolizumab. |
| Area Under Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of Nemolizumab | Pre-dose, 12 hours, 24 hours, Days 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 22, 29, 36, 43, 50, 57, 71, and 85 post-dose | AUC0-inf was defined as area under the plasma concentration-time curve from time 0 to infinity according to the equation: AUC0-inf = AUClast + Clast/λz; where λz = slope of the regression line of the terminal phase of the plasma concentration versus time curve, in semi-logarithmic scale; and Clast = last measurable drug concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Serum Concentration (Tmax) of Nemolizumab | Pre-dose, 12 hours, 24 hours, Days 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 22, 29, 36, 43, 50, 57, 71, and 85 post-dose | Tmax was defined as the time taken to reach the maximum observed serum concentration. |
| Area Under the Concentration-time Curve Over the Specified Interval (AUC0-4 Weeks) of Nemolizumab | Pre-dose, 12 hours, 24 hours, Days 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 22 and 29 post-dose | AUC0-4 weeks was defined as area under the concentration-time curve from time 0 to 4 weeks after study drug administration calculated with the linear trapezoidal method. |
| Number of Participants With Positive Anti-drug Antibodies (ADA) Response Against Nemolizumab | Pre-dose, Day 29 and 85 post-dose | ADA positive was defined as a sample that was evaluated as positive in both the ADA screening and confirmatory assays. ADA positive participants was defined as participants who had at least 1 positive ADA result. |
| Half-life (t1/2) of Nemolizumab | Pre-dose, 12 hours, 24 hours, Days 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 22, 29, 36, 43, 50, 57, 71, and 85 post-dose | t1/2 is defined as time required for the concentration of the drug to reach half of its original value. |
| Area Under Concentration-time Curve From Administration to the Last Observed Concentration Time t (AUC0-last) of Nemolizumab | Pre-dose, 12 hours, 24 hours, Days 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 22, 29, 36, 43, 50, 57, 71, and 85 post-dose | AUC0-last was defined as area under the concentration-time curve from administration to the last observed concentration time t, calculated with the linear trapezoidal method. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 2 sites in United States from 11 August 2022 to 08 December 2022.
Pre-assignment details
A total of 192 participants were randomized in two treatment group. 96 participants received nemolizumab with auto-injector (AI) and remaining 96 participants received nemolizumab with dual chamber syringe (DCS).
Participants by arm
| Arm | Count |
|---|---|
| Nemolizumab With AI Participants received a 60 mg dose of nemolizumab as 2 successive SC injections of 30 mg nemolizumab at either of the same location i.e., abdomen, front upper thigh, or outer upper arm and on the same side with injection sites at least 1 inch (2.5 cm) apart with AI on Day 0 (injection day). | 96 |
| Nemolizumab With DCS Participants received a 60-mg dose of nemolizumab as 2 successive SC injections of 30 mg nemolizumab at either of the same location i.e., abdomen, front upper thigh, or outer upper arm and on the same side with injection sites at least 1 inch (2.5 cm) apart with DCS on Day 0 (injection day). | 96 |
| Total | 192 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Nemolizumab With DCS | Total | Nemolizumab With AI |
|---|---|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 12.52 | 41.5 years STANDARD_DEVIATION 12.11 | 40.9 years STANDARD_DEVIATION 11.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 51 Participants | 104 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants | 88 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 17 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 9 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 80 Participants | 162 Participants | 82 Participants |
| Sex: Female, Male Female | 62 Participants | 117 Participants | 55 Participants |
| Sex: Female, Male Male | 34 Participants | 75 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 96 | 0 / 96 |
| other Total, other adverse events | 41 / 96 | 54 / 96 |
| serious Total, serious adverse events | 0 / 96 | 0 / 96 |
Outcome results
Primary
Area Under Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of Nemolizumab
AUC0-inf was defined as area under the plasma concentration-time curve from time 0 to infinity according to the equation: AUC0-inf = AUClast + Clast/λz; where λz = slope of the regression line of the terminal phase of the plasma concentration versus time curve, in semi-logarithmic scale; and Clast = last measurable drug concentration.
Time frame: Pre-dose, 12 hours, 24 hours, Days 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 22, 29, 36, 43, 50, 57, 71, and 85 post-dose
Population: Analysis was performed on PK population which included all randomized participants who received the dose of nemolizumab and provided evaluable data that can be used for the PK analyses. Here, 'overall number of participants analyzed, N' signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemolizumab With AI | Area Under Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of Nemolizumab | 270 micrograms*day per milliliter | Standard Deviation 85.8 |
| Nemolizumab With DCS | Area Under Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of Nemolizumab | 279 micrograms*day per milliliter | Standard Deviation 89.7 |
Primary
Maximum Observed Plasma Concentration (Cmax) of Nemolizumab
Cmax was defined as the observed maximum serum concentration of nemolizumab. Cmax was used to measure the rate of absorption of nemolizumab.
Time frame: Pre-dose, 12 hours, 24 hours, Days 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 22, 29, 36, 43, 50, 57, 71, and 85 post-dose
Population: Analysis was performed on pharmacokinetics (PK) population which included all randomized participants who received the dose of nemolizumab and provided evaluable data that can be used for the PK analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemolizumab With AI | Maximum Observed Plasma Concentration (Cmax) of Nemolizumab | 8.00 micrograms per milliliter (mcg/mL) | Standard Deviation 2.34 |
| Nemolizumab With DCS | Maximum Observed Plasma Concentration (Cmax) of Nemolizumab | 7.51 micrograms per milliliter (mcg/mL) | Standard Deviation 2.31 |
Secondary
Area Under Concentration-time Curve From Administration to the Last Observed Concentration Time t (AUC0-last) of Nemolizumab
AUC0-last was defined as area under the concentration-time curve from administration to the last observed concentration time t, calculated with the linear trapezoidal method.
Time frame: Pre-dose, 12 hours, 24 hours, Days 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 22, 29, 36, 43, 50, 57, 71, and 85 post-dose
Population: Analysis was performed on PK population which included all randomized participants who received the dose of nemolizumab and provided evaluable data that can be used for the PK analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemolizumab With AI | Area Under Concentration-time Curve From Administration to the Last Observed Concentration Time t (AUC0-last) of Nemolizumab | 250 micrograms*day per milliliter | Standard Deviation 73.6 |
| Nemolizumab With DCS | Area Under Concentration-time Curve From Administration to the Last Observed Concentration Time t (AUC0-last) of Nemolizumab | 260 micrograms*day per milliliter | Standard Deviation 75.4 |
Secondary
Area Under the Concentration-time Curve Over the Specified Interval (AUC0-4 Weeks) of Nemolizumab
AUC0-4 weeks was defined as area under the concentration-time curve from time 0 to 4 weeks after study drug administration calculated with the linear trapezoidal method.
Time frame: Pre-dose, 12 hours, 24 hours, Days 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 22 and 29 post-dose
Population: Analysis was performed on PK population which included all randomized participants who received the dose of nemolizumab and provided evaluable data that can be used for the PK analyses. Here, 'overall number of participants analyzed, N' signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemolizumab With AI | Area Under the Concentration-time Curve Over the Specified Interval (AUC0-4 Weeks) of Nemolizumab | 157 micrograms*day per milliliter | Standard Deviation 37.9 |
| Nemolizumab With DCS | Area Under the Concentration-time Curve Over the Specified Interval (AUC0-4 Weeks) of Nemolizumab | 155 micrograms*day per milliliter | Standard Deviation 39.8 |
Secondary
Half-life (t1/2) of Nemolizumab
t1/2 is defined as time required for the concentration of the drug to reach half of its original value.
Time frame: Pre-dose, 12 hours, 24 hours, Days 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 22, 29, 36, 43, 50, 57, 71, and 85 post-dose
Population: Analysis was performed on PK population which included all randomized participants who received the dose of nemolizumab and provided evaluable data that can be used for the PK analyses. Here, 'overall number of participants analyzed, N' signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemolizumab With AI | Half-life (t1/2) of Nemolizumab | 18.0 days | Standard Deviation 5.91 |
| Nemolizumab With DCS | Half-life (t1/2) of Nemolizumab | 18.5 days | Standard Deviation 4.52 |
Secondary
Number of Participants With Positive Anti-drug Antibodies (ADA) Response Against Nemolizumab
ADA positive was defined as a sample that was evaluated as positive in both the ADA screening and confirmatory assays. ADA positive participants was defined as participants who had at least 1 positive ADA result.
Time frame: Pre-dose, Day 29 and 85 post-dose
Population: Analysis was performed on safety population that included all randomized participants who received the single dose of nemolizumab and was the primary population for all safety data. Here, 'overall number of participants analyzed, N' signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nemolizumab With AI | Number of Participants With Positive Anti-drug Antibodies (ADA) Response Against Nemolizumab | Pre-dose: ADA postive | 6 Participants |
| Nemolizumab With AI | Number of Participants With Positive Anti-drug Antibodies (ADA) Response Against Nemolizumab | Day 29: ADA positive | 2 Participants |
| Nemolizumab With AI | Number of Participants With Positive Anti-drug Antibodies (ADA) Response Against Nemolizumab | Day 85: ADA positive | 2 Participants |
| Nemolizumab With DCS | Number of Participants With Positive Anti-drug Antibodies (ADA) Response Against Nemolizumab | Pre-dose: ADA postive | 8 Participants |
| Nemolizumab With DCS | Number of Participants With Positive Anti-drug Antibodies (ADA) Response Against Nemolizumab | Day 29: ADA positive | 4 Participants |
| Nemolizumab With DCS | Number of Participants With Positive Anti-drug Antibodies (ADA) Response Against Nemolizumab | Day 85: ADA positive | 8 Participants |
Secondary
Time to Reach Maximum Observed Serum Concentration (Tmax) of Nemolizumab
Tmax was defined as the time taken to reach the maximum observed serum concentration.
Time frame: Pre-dose, 12 hours, 24 hours, Days 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 22, 29, 36, 43, 50, 57, 71, and 85 post-dose
Population: Analysis was performed on PK population which included all randomized participants who received the dose of nemolizumab and provided evaluable data that can be used for the PK analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nemolizumab With AI | Time to Reach Maximum Observed Serum Concentration (Tmax) of Nemolizumab | 4.99 days |
| Nemolizumab With DCS | Time to Reach Maximum Observed Serum Concentration (Tmax) of Nemolizumab | 5.99 days |