A Study to Evaluate Emapalumab in Japanese Healthy Volunteers.

Overview

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.

Full Title of Study: “A Randomized, Double-blinded, Placebo-controlled, Single Center, Phase I Study to Evaluate Pharmacokinetics, Pharmacodynamics and Safety of Emapalumab After a Single Intravenous Dose in Japanese Healthy Volunteers.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Other
    • Masking: Single (Care Provider)
  • Study Primary Completion Date: May 2021

Interventions

  • Drug: NI-0501
    • Emapalumab single i.v infusion (1 mg/kg)
  • Drug: Saline
    • Saline single i.v infusion

Arms, Groups and Cohorts

  • Active Comparator: Emapalumab
    • Emapalumab i.v infusion
  • Placebo Comparator: Placebo
    • Saline i.v. infusion

Clinical Trial Outcome Measures

Primary Measures

  • Pharmacokinetic Assessment by Cmax
    • Time Frame: Up to 14 weeks
    • Peak plasma concentration
  • Pharmacokinetic Assessment by Tmax
    • Time Frame: Up to week 14 after infusion
    • Time of maximum plasma concentration
  • Pharmacokinetic Assessment by CEOI
    • Time Frame: Up to week 14 after infusion
    • Concentration at the end of the infusion
  • Pharmacokinetic Assessment by AUClast
    • Time Frame: Up to week 14 after infusion
    • Area under the concentration-time curve
  • Pharmacokinetic Assessment by AUCinf
    • Time Frame: Up to week 14 after infusion
    • Area under the concentration-time curve extrapolated to infinity
  • Pharmacokinetic Assessment by t1/2
    • Time Frame: Up to week 14 after infusion
    • Terminal elimination half-life
  • Pharmacokinetic Assessment by clearence (CL)
    • Time Frame: Up to week 14 after infusion
    • Total plasma clearance
  • Pharmacokinetic Assessment by Vss
    • Time Frame: Up to week 14 after infusion
    • Steady state volume of distribution

Secondary Measures

  • Safety assessment by registered Adverse events
    • Time Frame: From day of treatment up to 14 weeks
    • Number of subjects reporting adverse events
  • Change in levels of Aspartate aminotransferase (AST)
    • Time Frame: Up to week 14 after infusion
    • Measured in U/L
  • Change in levels of Alanine aminotransferase (ALT)
    • Time Frame: Up to week 14 after infusion
    • Measured in U/L
  • Change in levels of Direct Bilirubin
    • Time Frame: Up to week 14 after infusion
    • Measured in umol/L
  • Change in levels of Total Bilirubin
    • Time Frame: Up to week 14 after infusion
    • Measured in umol/L
  • Change in levels of Uric acid
    • Time Frame: Up to week 14 after infusion
    • Measured in mg/dL
  • Change in levels of Alkaline phosphatase
    • Time Frame: Up to week 14 after infusion
    • Measured in IU/L
  • Change in levels of Total protein
    • Time Frame: Up to week 14 after infusion
    • Measured in g/dL
  • Change in levels of Albumin
    • Time Frame: Up to week 14 after infusion
    • Measured in g/L
  • Change in levels of Prothrombin Time/International Normalized Ratio (PTINR)
    • Time Frame: Up to week 14 after infusion
    • Measured in seconds
  • Change in levels of Fibrinogen
    • Time Frame: Up to week 14 after infusion
    • Measured in g/L
  • Change in levels of Complement C3/C4
    • Time Frame: Up to week 14 after infusion
    • Measured in mg/dL
  • Change in levels of Cardiac troponin
    • Time Frame: Up to week 14 after infusion
    • Measured in ng/mL
  • Change in levels of Creatinine
    • Time Frame: Up to week 14 after infusion
    • Measured in umol/L
  • Change in levels of C-reactive protein (CRP)
    • Time Frame: Up to week 14 after infusion
    • Measured in mg/L
  • Change in levels of Sodium
    • Time Frame: Up to week 14 after infusion
    • Measured in mmol/L
  • Change in levels of Potassium
    • Time Frame: Up to week 14 after infusion
    • Measured in mmol/L
  • Change in levels of Calcium
    • Time Frame: Up to week 14 after infusion
    • Measured in mmol/L
  • Change in levels of Glucose
    • Time Frame: Up to week 14 after infusion
    • Measured in mmol/L
  • Change in levels of HDL
    • Time Frame: Up to week 14 after infusion
    • Measured in mg/dL
  • Change in levels of LDL
    • Time Frame: Up to week 14 after infusion
    • Measured in mg/dL
  • Change in levels of BUN/Urea haematology
    • Time Frame: Up to week 14 after infusion
    • Measured in mg/dL
  • Change in levels of Hemoglobine
    • Time Frame: Up to week 14 after infusion
    • Measured in g/L
  • Change in levels of Hematocrit
    • Time Frame: Up to week 14 after infusion
    • Measured in %
  • Change in levels of Platelet count
    • Time Frame: Up to week 14 after infusion
    • Measured in 10 9/L
  • Change in levels of White blood cells
    • Time Frame: Up to week 14 after infusion
    • Measured in 10 9/L
  • Change in levels of Red blood cells
    • Time Frame: Up to week 14 after infusion
    • Measured in 10 12/L
  • Change in levels of Differential blood count
    • Time Frame: Up to week 14 after infusion
    • Measured in %
  • Change in levels of Immunoglobulin levels
    • Time Frame: Up to week 14 after infusion
    • Measured in U/mL
  • Change in levels of Coagulation profile (APTT)
    • Time Frame: Up to week 14 after infusion
    • Measured in seconds
  • Presence of anti-drug antibodies and neutralizing antibodies
    • Time Frame: Up to week 14 after infusion
    • Number of subjects reporting ADA and NAb

Participating in This Clinical Trial

Inclusion Criteria

1. Healthy Japanese (male and female) subjects between 20 and 50 years (inclusive). 2. 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) 3. 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 4. Haemoglobin level equal or above 11 g/dL in females and 13 g/dL in males. 5. Subject having C-reactive protein (CRP) levels within the normal range (local laboratory range). 6. 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. 7. Signed informed consent. Exclusion Criteria:

1. 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 2. Any clinically significant abnormality on the screening electrocardiogram (ECG), as judged by the investigator 3. 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 4. Actual presence or occurrence of any bacterial, viral, parasitic or fungal infection within the 4 weeks preceding IMP infusion 5. 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 6. Positive stool test for Shigella or salmonella infection. 7. Positive results from Sars-CoV-2 screening within 96 hours prior to randomization 8. History or clinical evidence suggestive of active or latent tuberculosis at screening. (i.e. test positive to the interferon gamma (IFNγ)-release assay) 9. History or presence of any severe allergic reactions 10. History of hypersensitivity or allergy to any component of emapalumab and/or valaciclovir hydrochloride 11. History or presence of any malignancy 12. History or presence of drug or alcohol abuse 13. Subject with a smoking history within the last 6 months prior to the time of screening 14. Immunization with a live vaccine within 6 weeks prior to receiving IMP and 12 weeks after IMP infusion 15. Experience of collected blood corresponding to any of the following

  • Component blood donation within 2 weeks before the screening test and within 2 weeks before the first study drug administration – Collection of 200 mL or more of blood (blood donation, etc.) from 4 weeks before the screening test until admission – Male subject who has experience of collection of 400 mL or more of blood (blood donation, etc.) from 12weeks before the screening test until admission. – Female subject who has experience of collection of 400 mL or more of blood (blood donation, etc.) from 16weeks before the screening test until admission. 16. Usage of any prescription drugs within 2 weeks or over-the-counter medication including herbal supplements (with the exception of multi-vitamins) within 1 week before IMP administration without prior approval from the investigator 17. Positive pregnancy test at screening or Day -1 18. Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol 19. Enrollment in another concurrent clinical interventional study, or intake of another IMP, within four months or 5 half-lives (of the other IMP) prior to inclusion in this study

Gender Eligibility: All

Minimum Age: 20 Years

Maximum Age: 50 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Swedish Orphan Biovitrum
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Kenichi Furihata, MD, PhD, Principal Investigator, P-One Clinic, 4F, View Tower Hachioji, 8-1, Yokamachi, Hachioji-shi, Tokyo 192-0071, Japan
  • Overall Contact(s)
    • Carl-Johan Treutiger, MD, PhD, +4686972000, CarlJohan.Treutiger@sobi.com

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.