A Study to Evaluate Emapalumab in Japanese Healthy Volunteers.
Condition: Rare Diseases
MeSH terms: Rare Diseases
Intervention: NI-0501; Saline
Intervention description: emapalumab single i.v infusion (1 mg/kg); Saline single i.v infusion
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Care Provider)
Masking description: Double blind
Enrollment: 8.0
Sex: All
Minimum age: 20 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility criteria:

        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