Phase 1
Completed N=8
A Study to Evaluate Emapalumab in Japanese Healthy Volunteers.
Source: ClinicalTrials.gov NCT04765553 ↗Enrolled (actual)
8
Serious AEs
0.0%
Results posted
Nov 2023
Primary outcomePrimary: The Maximum Observed Concentration of Emapalumab — 23980 ng/mL
Summary
This is a randomized, placebo controlled and double-blinded study to evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of a single dose (1 mg/kg) of emapalumab in adult healthy Japanese subjects.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Maximum Observed Concentration of Emapalumab |
23980 | — |
| PRIMARY The Time at Which the Maximum Concentration of Emapalumab is Observed |
2.000 | — |
| PRIMARY Concentration of Emapalumab at End of Infusion |
23230 | — |
| PRIMARY Area Under the Plasma Concentration-time Curve |
11690000 | — |
| PRIMARY Area Under the Concentration-time Curve Extrapolated to Infinity |
12430000 | — |
| PRIMARY Emapalumab Elimination Half-life |
634.9 | — |
| PRIMARY Apparent Total Body Clearance of Emapalumab From Plasma |
0.006136 | — |
| PRIMARY Steady State Volume of Distribution |
4.953 | — |
| SECONDARY Overall Summary of Adverse Events |
3; 1; 3; 0; 0; 0 | — |
| SECONDARY Change in Levels of Aspartate Aminotransferase |
0.5; 2.5; -0.5; 5.0; -2.5; 1.5 | — |
| SECONDARY Change in Levels of Alanine Aminotransferase |
0.5; 1.0; 0.0; 2.5; -2.0; 0.5 | — |
| SECONDARY Change in Levels of Direct Bilirubin |
0.15; 0.05; 0.15; 0.00; 0.10; -0.05 | — |
| SECONDARY Change in Levels of Total Bilirubin |
0.35; 0.30; 0.55; 0.10; 0.15; -0.10 | — |
| SECONDARY Change in Levels of Uric Acid |
0.15; 0.10; 0.40; 0.15; 0.40; 0.15 | — |
| SECONDARY Change in Levels of Alkaline Phosphatase |
-34.0; 16.0; -26.5; 16.0; -23.5; 22.0 | — |
| SECONDARY Change in Levels of Total Protein |
0.25; 0.30; 0.25; 0.25; 0.20; 0.35 | — |
| SECONDARY Change in Levels of Albumin |
0.10; 0.35; 0.05; 0.30; -0.15; 0.20 | — |
| SECONDARY Change in Levels of Prothrombin Time/International Normalized Ratio |
0.065; -0.005; 0.045; -0.035; 0.075; 0.010 | — |
| SECONDARY Change in Levels of Fibrinogen |
6.0; 49.5; 53.0; 103.5; 60.0; -97.0 | — |
| SECONDARY Change in Levels of Complement C3 |
4.0; 11.5; 3.5; 4.5; 12.5; 9.0 | — |
| SECONDARY Change in Levels of Creatinine |
0.030; 0.095; 0.010; 0.020; 0.010; 0.025 | — |
| SECONDARY Change in Levels of C-reactive Protein |
0.000; -0.015; 0.105; 0.030; 0.645; 0.025 | — |
| SECONDARY Change in Levels of Sodium |
-1.0; 3.5; -0.5; 1.5; -1.5; 2.0 | — |
| SECONDARY Change in Levels of Potassium |
0.00; 0.60; 0.00; 0.15; 0.15; 0.40 | — |
| SECONDARY Change in Levels of Calcium |
-0.05; 0.40; 0.00; 0.15; -0.10; 0.30 | — |
| SECONDARY Change in Levels of Glucose |
-9.0; -3.0; -1.0; 0.5; 0.5; 3.0 | — |
| SECONDARY Change in Levels of HDL |
-2.0; 0.0; -3.5; -1.0; -4.0; 1.0 | — |
| SECONDARY Change in Levels of LDL |
11.0; 16.5; 5.5; 17.0; 3.5; 19.5 | — |
| SECONDARY Change in Levels of BUN/Urea Haematology |
-1.35; -1.60; -0.55; 2.55; -1.05; 1.30 | — |
| SECONDARY Change in Levels of Hemoglobin |
0.4; 0.75; 0.35; 0.55; 0.20; 0.45 | — |
| SECONDARY Change in Levels of Hematocrit |
1.6; 2.80; 1.10; 2.10; 0.70; 1.55 | — |
| SECONDARY Change in Levels of Platelet Count |
0.40; 1.20; -0.15; 1.10; -0.1; 1.40 | — |
| SECONDARY Change in Levels of Neutrophils |
-0.30; 0.35; 17.45; -0.40; 9.70; -0.85 | — |
| SECONDARY Change in Levels of Red Blood Cells |
18; 27.0; 13.5; 20.0; 9.0; 15.0 | — |
| SECONDARY Change in Levels of Immunoglobulin Levels |
69.5; 119.5; 28.5; 72.0; 5.0; 78 | — |
| SECONDARY Change in Levels of Coagulation Profile |
0.85; 0.4; -0.30; -0.65; 0.4; 1.80 | — |
| SECONDARY Presence of Anti-drug Antibodies and Neutralizing Antibodies |
0; 0 | — |
| SECONDARY Change in Levels of Complement C4 |
0.0; 2.5; 1.0; 2.0; 3.0; 3.0 | — |
| SECONDARY Presence of Neutralizing Antibodies |
NA | — |
Eligibility Criteria
Inclusion Criteria
- Healthy Japanese (male and female) subjects between 20 and 50 years (inclusive).
- Body weight greater than 45 kg (female) or 50 kg (male) and a body mass index (BMI) >18 kg/m2 and < 30 kg/m2 (BMI= weight (kg) / height (m)²)
- Vital signs in the following range:
- Axillary body temperature: 35.2 - 37.5℃
- Heart rate (after at least 3 minutes of rest, measured in the supine position): 40-100 bpm
- BP < 140/80, mean of 3 readings after 15 minutes rest
- Haemoglobin level equal or above 11 g/dL in females and 13 g/dL in males.
- Subject having C-reactive protein (CRP) levels within the normal range (local laboratory range).
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant having agreed to use highly effective methods of contraception during dosing and for 6 months after receiving IMP.
Highly effective contraception methods include:
- Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
- Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient, otherwise highly effective methods to be applied.
- Use of oral (estrogen and progesterone) hormonal method of contraception, or placement of an intrauterine device (IUD) or intrauterine system (IUS)
- In case of use of oral contraception women should have been stable on the same brand (or generic equivalent) for a minimum of 3 months before taking study treatment.
Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago.
- Signed informed consent.
Exclusion Criteria
- Any clinically significant abnormality in the results of the safety laboratory tests. Subjects presenting a minor deviation from laboratory ranges could be enrolled if the investigator judge it to be non-clinically significant
- Any clinically significant abnormality on the screening electrocardiogram (ECG), as judged by the investigator
- History or clinical evidence of any disease and/or existence of any surgical or medical condition that might interfere with the absorption, distribution, metabolism or excretion of the study drugs
- Actual presence or occurrence of any bacterial, viral, parasitic or fungal infection within the 4 weeks preceding IMP infusion
- Positive results from serology examination for Hepatitis B surface antigen (HBsAg), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV), syphilis (TP-antigen and RPR) or pregnancy
- Positive stool test for Shigella or salmonella infection.
- Positive results from Sars-CoV-2 screening within 96 hours prior to randomization
- History or clinical evidence suggestive of active or latent tuberculosis at screening. (i.e. test positive to the interferon gamma (IFNγ)-release assay)
- History or presence of any severe allergic reactions
- History of hypersensitivity or allergy to any component of emapalumab and/or valaciclovir hydrochloride
- History or presence of any malignancy
- History or presence of drug or alcohol abuse
- Subject with a smoking history within the last 6 months prior to the time of screening
- Immunization with a live vaccine within 6 weeks prior to recei
Data sourced from ClinicalTrials.gov (NCT04765553). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.