Clinical trial NCT04765553: A Study to Evaluate Emapalumab in Japanese Healthy Volunteers.
Official title: 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: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rare Diseases
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
First posted: 2021-02-21
Enrollment: 8
Sex: ALL
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.

Detailed description: This is a randomized, placebo-controlled and double-blinded study to evaluate the PK, PD and safety of a single dose (1 mg/kg) of emapalumab in adult healthy Japanese subjects, performed in Japan. The subjects, 8 in total, will be randomized to receive either emapalumab or matching placebo in a 3:1 ratio (emapalumab: placebo).

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

Primary outcomes:
measure: The Maximum Observed Concentration of Emapalumab
timeFrame: Day 1 preinfusion, 1hr, 2hrs, 4hrs, 8hrs, 10hrs post dose, day 2, 3, 5, 8, week 2, 4, 6, 8, 10, 12, study completion week 14 or Withdrawal
measure: The Time at Which the Maximum Concentration of Emapalumab is Observed
timeFrame: Day 1 preinfusion, 1hr, 2 hrs, 4hrs, 8hrs, 10hrs, Day 2, 3, 5, 8, Week 2, 4, 6, 8, 10, 12, study completion week 14 or at Withdrawal
measure: Concentration of Emapalumab at End of Infusion
timeFrame: Day 1 preinfusion, 1hr, 2 hrs, 4hrs, 8hrs, 10hrs, Day 2, 3, 5, 8, Week 2, 4, 6, 8, 10, 12, study completion week 14 or at Withdrawal
measure: Area Under the Plasma Concentration-time Curve
timeFrame: Day 1 preinfusion, 1hr, 2 hrs, 4hrs, 8hrs, 10hrs, Day 2, 3, 5, 8, Week 2, 4, 6, 8, 10, 12, study completion week 14 or at Withdrawal
measure: Area Under the Concentration-time Curve Extrapolated to Infinity
timeFrame: Day 1 preinfusion, 1hr, 2 hrs, 4hrs, 8hrs, 10hrs, Day 2, 3, 5, 8, Week 2, 4, 6, 8, 10, 12, study completion week 14 or at Withdrawal
measure: Emapalumab Elimination Half-life
timeFrame: Day 1 preinfusion, 1hr, 2 hrs, 4hrs, 8hrs, 10hrs, Day 2, 3, 5, 8, Week 2, 4, 6, 8, 10, 12, study completion week 14 or at Withdrawal
measure: Apparent Total Body Clearance of Emapalumab From Plasma
timeFrame: Day 1 preinfusion, 1hr, 2 hrs, 4hrs, 8hrs, 10hrs, Day 2, 3, 5, 8, Week 2, 4, 6, 8, 10, 12, study completion week 14 or at Withdrawal
measure: Steady State Volume of Distribution
timeFrame: Day 1 preinfusion, 1hr, 2 hrs, 4hrs, 8hrs, 10hrs, Day 2, 3, 5, 8, Week 2, 4, 6, 8, 10, 12, study completion week 14 or at Withdrawal
Secondary outcomes:
measure: Overall Summary of Adverse Events
timeFrame: Continuously from start of emapalumab infusion up to 14 weeks
measure: Change in Levels of Aspartate Aminotransferase
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Alanine Aminotransferase
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Direct Bilirubin
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Total Bilirubin
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Uric Acid
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Alkaline Phosphatase
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Total Protein
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Albumin
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Prothrombin Time/International Normalized Ratio
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Fibrinogen
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Complement C3
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Creatinine
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of C-reactive Protein
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Sodium
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Potassium
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Calcium
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Glucose
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of HDL
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of LDL
timeFrame: Baselilne, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of BUN/Urea Haematology
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Hemoglobin
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Hematocrit
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Platelet Count
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Neutrophils
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Red Blood Cells
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Immunoglobulin Levels
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Change in Levels of Coagulation Profile
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Presence of Anti-drug Antibodies and Neutralizing Antibodies
timeFrame: From Day 1 to Week 14
measure: Change in Levels of Complement C4
timeFrame: Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14)
measure: Presence of Neutralizing Antibodies
timeFrame: From Day 1 to Week 14
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: P-One Clinic
Study officials:
affiliation: P-One Clinic, 4F, View Tower Hachioji, 8-1, Yokamachi, Hachioji-shi, Tokyo 192-0071, Japan
name: Kenichi Furihata, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: