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CompletedNCT03401671Updated Jun 3, 2021Results posted

Study of Lanadelumab in Healthy Japanese and Matched Caucasian Adult Subjects

A Phase 1 interventional study of Lanadelumab in Healthy Volunteers, sponsored by Shire. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-06-03.

Sponsored by Shire · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
32
Allocation
Non-randomized
Ages
18 Years to 55 Years
Sex
All
01

Study summary

The purpose of this study is to evaluate the pharmacokinetics (PK), safety and tolerability and pharmacodynamics (PD) of lanadelumab in healthy adult Japanese subjects and matched non-Hispanic healthy adult Caucasian subjects.

02

Conditions studied

  • Healthy Volunteers

Keywords

  • Lanadelumab
03

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Ability to voluntarily provide written, signed, and dated informed consent as applicable to participate in the study.
  • An understanding, ability, and willingness to fully comply with study procedures and restrictions.
  • Age 18-55, inclusive, at the time of consent. The date of signature of the informed consent is defined as the beginning of the Screening Period. This inclusion criterion will only be assessed at the first screening visit.

  • Subjects must be either:

    1. A subject of Japanese descent born in Japan, who has resided outside of Japan for no longer than 5 years and is of Japanese parentage, defined as having 2 Japanese parents and 4 Japanese grandparents, all born in Japan.
    2. A non-Hispanic, Caucasian subject who has 2 non-Hispanic, Caucasian parents and 4 non-Hispanic, Caucasian grandparents.
  • Male or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential.
  • Considered "healthy" by the investigator. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, as well as a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, and urinalysis.
  • Body mass index between 18.5-33 kilograms per square meter (kg/m\^2), inclusive, with a body weight greater than or equal to (≥) 45 kg (99 pounds [lbs]). This inclusion criterion will only be assessed at the screening visit.
  • Willing and able to consume standardized meals during the confinement period of the study. All subjects will be required to consume the identical meals on study days when serial PK and PD blood samples are collected.

Exclusion criteria

Exclusion Criteria:

  • History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gall bladder removal, or current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments.
  • Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to complete the study, or any condition that presents undue risk from the investigational product or procedures.
  • Known or suspected intolerance or hypersensitivity to the investigational product, closely related compounds, or any of the stated ingredients.
  • Significant illness, as judged by the investigator, within 2 weeks of the dose of investigational product.
  • Known history of alcohol or other substance abuse within the last year, per the investigator.
  • Donation of blood or blood products (example [e.g], plasma or platelets) within 60 days prior to receiving the dose of investigational product.

  • Within 30 days prior to the dose of investigational product:

    1. Have used an investigational product (if elimination half-life is less than [\<] 6 days, otherwise 5 half-lives).
    2. Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this Shire-sponsored study.
  • Confirmed systolic blood pressure (BP) greater than (>) 139 millimeter of mercury (mmHg) or \<89mmHg, and diastolic BP >89mmHg or \<49mmHg.
  • Twelve-lead ECG values (average of triplicate readings) demonstrating QTc >450 milliseconds (msec) (males) or >470msec (females) at the Screening Visit or Day -1.
  • Positive screen for drugs of abuse (that is, amphetamines, benzodiazepines, barbiturates, cocaine, marijuana, opiates, phencyclidine) at Screening, or drugs of abuse or alcohol on Day -1.
  • Male subjects who consume more than 21 units of alcohol per week or 3 units per day. Female subjects who consume more than 14 units of alcohol per week or 2 units per day. One alcohol unit=1 beer or 1 wine (5 ounce [oz]/150 milliliter [mL]) or 1 liquor (1.5oz/40mL) or 0.75oz alcohol.
  • Positive human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), or hepatitis C virus.(HCV) antibody screen.
  • Use of tobacco in any form (eg, smoking or chewing) or other nicotine-containing products in any form (eg, gum, patch, electronic). Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the dose of investigational product.
  • Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches. One caffeine unit is contained in the following items: one 6oz (180mL) cup of coffee, two 12oz (360mL) cans of cola, one 12oz cup of tea, and three 1oz (85g) chocolate bars. Decaffeinated coffee, tea, or cola are not considered to contain caffeine.
  • Current use of any medication (including over-the-counter, herbal, or homeopathic preparations; with the exception of hormonal replacement therapy or hormonal contraceptives). Current use is defined as use within 14 days of the dose of investigational product.
  • Abnormal laboratory values considered clinically significant, as determined by the investigator at Screening or Day -1.
  • History of any clinically significant surgery or procedure within 8 weeks of receiving the dose of investigational product, as determined by the investigator.
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
32 participants (actual)

Study arms

  • Experimental
    Japanese

    Healthy subjects of Japanese descent will receive a single dose of 300 milligrams (mg) lanadelumab subcutaneous (SC) injection in the abdomen.

    Drug: Lanadelumab

  • Experimental
    Non-Hispanic Caucasians

    Healthy Non-Hispanic Caucasian subjects will receive a single dose of 300 mg lanadelumab SC injection in the abdomen

    Drug: Lanadelumab

Interventions

  • DrugLanadelumab

    SC injection of 300mg in 2mL (150 mg/mL) solution of lanadelumab will be administered as a single dose injection in the abdomen.

    Also known as: SHP643

05

What researchers measure

Primary outcomes

  1. Maximum Observed Plasma Concentration (Cmax) of Lanadelumab

    Cmax is the maximum observed plasma concentration of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    Time frame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

  2. Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of Lanadelumab

    Tmax of Lanadelumab was presented.

    Time frame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

  3. Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab

    AUC(0-last) of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    Time frame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

  4. Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Lanadelumab

    AUC(0-infinity) of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    Time frame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

  5. Terminal Elimination Rate Constant (Lambda z) for Lanadelumab

    Lambda z of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    Time frame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

  6. Terminal Half-life (t12) of Lanadelumab

    t1/2 of Lanadelumab was presented.

    Time frame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

  7. Apparent Clearance (CL/F) of Lanadelumab

    CL/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    Time frame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

  8. Apparent Volume of Distribution (Vz/F) of Lanadelumab

    Vz/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    Time frame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

  9. Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab

    Body-weight adjusted AUC(0-last) of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    Time frame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

  10. Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) in Plasma of Lanadelumab

    Body-weight adjusted AUC(0-infinity) of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    Time frame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

  11. Body-weight Adjusted Maximum Observed Plasma Concentration (Cmax) of Lanadelumab

    Body-weight adjusted Cmax of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    Time frame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

  12. Body-weight Adjusted Apparent Clearance (CL/F) of Lanadelumab

    Body-weight adjusted CL/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    Time frame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

  13. Body-weight Adjusted Apparent Volume of Distribution (Vz/F) of Lanadelumab

    Body-weight adjusted Vz/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    Time frame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

Secondary outcomes

  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality

    An adverse event (AE) is any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are defined as AEs with onset at the time of or following the first exposure to study drug, or medical conditions present prior to the start of study drug but increasing in severity or relationship at the time of or following the start of treatment, up to the last follow-up visit. Severity of an AE is determined by following definitions: Mild: An event that does not generally interfere with usual activities of daily living; Moderate: An event that interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participants; Severe: An AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.

    Time frame: From start of study drug administration up to follow-up (up to 115 days)

  2. Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event

    Clinical laboratory assessments include hematology, clinical chemistry, coagulation and urinalysis. The investigator will assess out-of-range clinical laboratory values for clinical significance, to indicate whether or not the values are clinically significant. Any changes from baseline in clinical laboratory results which are deemed clinically significant by the investigator are to be recorded as an AE.

    Time frame: From start of study drug administration up to follow-up (up to 115 days)

  3. Number of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event

    Vital sign assessments include blood pressure, pulse rate and body temperature. Any changes from baseline in vital signs which are deemed clinically significant by the investigator are to be recorded as an AE.

    Time frame: From start of study drug administration up to follow-up (up to 115 days)

  4. Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event

    Twelve-lead ECG will be performed after 5 minutes of rest in the supine position. Any change in ECG assessments which are deemed clinically significant by the investigator are to be reported as AE.

    Time frame: From start of study drug administration up to follow-up (up to 115 days)

  5. Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points

    Plasma samples were analyzed for presence of antidrug antibodies to lanadelumab. Participants who show positive results for lanadelumab antibodies were reported.

    Time frame: Day 1, 14, 28, 56, and 112 (End of Study/Early Termination [EOS/ET])

06

Results

Posted Jul 29, 2019

Participant flow

The study was conducted in the United States between 15 January 2018 (first participant first visit) and 30 May 2018 (last participant last visit).

Participant flow — Overall Study
MilestoneJapaneseNon-Hispanic Caucasians
Started1616
Completed1616
Not completed00

Outcome measures

PrimaryMaximum Observed Plasma Concentration (Cmax) of Lanadelumab

Cmax is the maximum observed plasma concentration of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.

Time frame:
Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
Reported as:
Geometric mean · microgram per milliliter (ug/mL)
Maximum Observed Plasma Concentration (Cmax) of Lanadelumab
microgram per milliliter (ug/mL)JapaneseNon-Hispanic Caucasians
Maximum Observed Plasma Concentration (Cmax) of Lanadelumab21.91 ± 3821.42 ± 25
Statistical analysis
  • Japanese vs Non-Hispanic Caucasians · Ratio of geometric least squares means: 1.0229 · 90% CI 0.8473 to 1.2349
PrimaryTime to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of Lanadelumab

Tmax of Lanadelumab was presented.

Time frame:
Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
Reported as:
Median · day
Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of Lanadelumab
dayJapaneseNon-Hispanic Caucasians
Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of Lanadelumab5.67 (2.00 to 6.11)5.00 (3.00 to 13.00)
PrimaryArea Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab

AUC(0-last) of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.

Time frame:
Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
Reported as:
Geometric mean · day*microgram per milliliter(day*ug/mL)
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab
day*microgram per milliliter(day*ug/mL)JapaneseNon-Hispanic Caucasians
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab510.6 ± 30547.6 ± 20
Statistical analysis
  • Japanese vs Non-Hispanic Caucasians · Ratio of geometric least squares means: 0.9324 · 90% CI 0.8016 to 1.0846
PrimaryArea Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Lanadelumab

AUC(0-infinity) of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

Time frame:
Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
Reported as:
Geometric mean · day*microgram per milliliter(day* ug/mL)
Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Lanadelumab
day*microgram per milliliter(day* ug/mL)JapaneseNon-Hispanic Caucasians
Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Lanadelumab515.0 ± 30552.7 ± 20
Statistical analysis
  • Japanese vs Non-Hispanic Caucasians · Ratio of geometric least squares means: 0.9318 · 90% CI 0.8005 to 1.0846
PrimaryTerminal Elimination Rate Constant (Lambda z) for Lanadelumab

Lambda z of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

Time frame:
Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
Reported as:
Geometric mean · per day
Terminal Elimination Rate Constant (Lambda z) for Lanadelumab
per dayJapaneseNon-Hispanic Caucasians
Terminal Elimination Rate Constant (Lambda z) for Lanadelumab0.04470 ± 90.04385 ± 11
PrimaryTerminal Half-life (t12) of Lanadelumab

t1/2 of Lanadelumab was presented.

Time frame:
Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
Reported as:
Median · day
Terminal Half-life (t12) of Lanadelumab
dayJapaneseNon-Hispanic Caucasians
Terminal Half-life (t12) of Lanadelumab15.54 (12.8 to 17.9)15.59 (12.4 to 19.1)
PrimaryApparent Clearance (CL/F) of Lanadelumab

CL/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

Time frame:
Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
Reported as:
Geometric mean · liter per day
Apparent Clearance (CL/F) of Lanadelumab
liter per dayJapaneseNon-Hispanic Caucasians
Apparent Clearance (CL/F) of Lanadelumab0.5826 ± 300.5428 ± 20
PrimaryApparent Volume of Distribution (Vz/F) of Lanadelumab

Vz/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

Time frame:
Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
Reported as:
Geometric mean · liter
Apparent Volume of Distribution (Vz/F) of Lanadelumab
literJapaneseNon-Hispanic Caucasians
Apparent Volume of Distribution (Vz/F) of Lanadelumab13.03 ± 2912.38 ± 22
PrimaryBody-weight Adjusted Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab

Body-weight adjusted AUC(0-last) of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.

Time frame:
Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
Reported as:
Geometric mean · day*ug/mL/kg
Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab
day*ug/mL/kgJapaneseNon-Hispanic Caucasians
Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab510.6 ± 30547.6 ± 20
PrimaryBody-weight Adjusted Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) in Plasma of Lanadelumab

Body-weight adjusted AUC(0-infinity) of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.

Time frame:
Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
Reported as:
Geometric mean · day*ug/mL/kg
Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) in Plasma of Lanadelumab
day*ug/mL/kgJapaneseNon-Hispanic Caucasians
Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) in Plasma of Lanadelumab8.012 ± 447.950 ± 27
PrimaryBody-weight Adjusted Maximum Observed Plasma Concentration (Cmax) of Lanadelumab

Body-weight adjusted Cmax of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

Time frame:
Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
Reported as:
Median · microgram per milliliter per kilogram
Body-weight Adjusted Maximum Observed Plasma Concentration (Cmax) of Lanadelumab
microgram per milliliter per kilogramJapaneseNon-Hispanic Caucasians
Body-weight Adjusted Maximum Observed Plasma Concentration (Cmax) of Lanadelumab0.3236 (0.125 to 0.722)0.3042 (0.196 to 0.709)
PrimaryBody-weight Adjusted Apparent Clearance (CL/F) of Lanadelumab

Body-weight adjusted CL/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

Time frame:
Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
Reported as:
Geometric mean · liter per day per kilogram (L/day/kg)
Body-weight Adjusted Apparent Clearance (CL/F) of Lanadelumab
liter per day per kilogram (L/day/kg)JapaneseNon-Hispanic Caucasians
Body-weight Adjusted Apparent Clearance (CL/F) of Lanadelumab0.009064 ± 230.007809 ± 20
PrimaryBody-weight Adjusted Apparent Volume of Distribution (Vz/F) of Lanadelumab

Body-weight adjusted Vz/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

Time frame:
Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
Reported as:
Geometric mean · liter per kilogram (L/kg)
Body-weight Adjusted Apparent Volume of Distribution (Vz/F) of Lanadelumab
liter per kilogram (L/kg)JapaneseNon-Hispanic Caucasians
Body-weight Adjusted Apparent Volume of Distribution (Vz/F) of Lanadelumab0.2028 ± 230.1781 ± 20
SecondaryNumber of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality

An adverse event (AE) is any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are defined as AEs with onset at the time of or following the first exposure to study drug, or medical conditions present prior to the start of study drug but increasing in severity or relationship at the time of or following the start of treatment, up to the last follow-up visit. Severity of an AE is determined by following definitions: Mild: An event that does not generally interfere with usual activities of daily living; Moderate: An event that interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participants; Severe: An AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.

Time frame:
From start of study drug administration up to follow-up (up to 115 days)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality
ParticipantsJapaneseNon-Hispanic Caucasians
Participants with Mild TEAE64
Participants with Moderate TEAE15
Participants with Severe TEAE00
Participants with Serious TEAE00
Participants with Non-Serious TEAE79
Participants with Causality (Death)00
SecondaryNumber of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event

Clinical laboratory assessments include hematology, clinical chemistry, coagulation and urinalysis. The investigator will assess out-of-range clinical laboratory values for clinical significance, to indicate whether or not the values are clinically significant. Any changes from baseline in clinical laboratory results which are deemed clinically significant by the investigator are to be recorded as an AE.

Time frame:
From start of study drug administration up to follow-up (up to 115 days)
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event
ParticipantsJapaneseNon-Hispanic Caucasians
Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event00
SecondaryNumber of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event

Vital sign assessments include blood pressure, pulse rate and body temperature. Any changes from baseline in vital signs which are deemed clinically significant by the investigator are to be recorded as an AE.

Time frame:
From start of study drug administration up to follow-up (up to 115 days)
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event
ParticipantsJapaneseNon-Hispanic Caucasians
Number of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event00
SecondaryNumber of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event

Twelve-lead ECG will be performed after 5 minutes of rest in the supine position. Any change in ECG assessments which are deemed clinically significant by the investigator are to be reported as AE.

Time frame:
From start of study drug administration up to follow-up (up to 115 days)
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event
ParticipantsJapaneseNon-Hispanic Caucasians
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event00
SecondaryNumber of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points

Plasma samples were analyzed for presence of antidrug antibodies to lanadelumab. Participants who show positive results for lanadelumab antibodies were reported.

Time frame:
Day 1, 14, 28, 56, and 112 (End of Study/Early Termination [EOS/ET])
Reported as:
Count of participants · Participants
Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points
ParticipantsJapaneseNon-Hispanic Caucasians
Participants with positive ADA: Day 100
Participants with positive ADA: Day 1400
Participants with positive ADA: Day 2800
Participants with positive ADA: Day 5600
Participants with positive ADA: Day 112 (EOS/ET)01

Adverse events

Collected over From start of study drug administration up to follow-up (up to 115 days). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Japanese0/16 (0%)0/16 (0%)7/16 (43.8%)
Non-Hispanic Caucasians0/16 (0%)0/16 (0%)9/16 (56.3%)
Most frequent other events
Showing 10 of 24
Most frequent other events
EventJapaneseNon-Hispanic Caucasians
Upper respiratory tract infectionInfections and infestations1/163/16
Back painMusculoskeletal and connective tissue disorders0/162/16
NauseaGastrointestinal disorders0/162/16
PharyngitisInfections and infestations0/162/16
HeadacheNervous system disorders1/162/16
DysmenorrhoeaReproductive system and breast disorders0/162/16
ArthralgiaMusculoskeletal and connective tissue disorders1/160/16
Abdominal painGastrointestinal disorders1/160/16
ConstipationGastrointestinal disorders1/160/16
Injection site erythemaGeneral disorders1/160/16

Baseline characteristics

Safety analysis set consisted of all participants who received at least 1 dose of lanadelumab.

Age, Continuous
Age, Continuous(Years)JapaneseNon-Hispanic CaucasiansTotal
Mean43.4 ± 7.8242.8 ± 6.4043.1 ± 7.04
Sex: Female, Male
Sex: Female, Male(Participants)JapaneseNon-Hispanic CaucasiansTotal
Female101020
Male6612
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)JapaneseNon-Hispanic CaucasiansTotal
Hispanic or Latino000
Not Hispanic or Latino161632
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)JapaneseNon-Hispanic CaucasiansTotal
American Indian or Alaska Native000
Asian16016
Native Hawaiian or Other Pacific Islander000
Black or African American000
White01616
More than one race000
Unknown or Not Reported000
07

Study locations

1 site
  • WCCT Global, Inc.
    Cypress, California 90630, United States
08

References and documents

Study documents

  • Study protocol · Nov 27, 2017
  • Statistical analysis plan · Jun 21, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting information: Study protocol, Sap, Icf, Csr

09

Registry details

Key details

Study ID
NCT03401671
Lead sponsor
Shire
Responsible party
Sponsor
First posted
Jan 17, 2018
Start date
Jan 15, 2018
Primary completion
May 30, 2018
Completion
May 30, 2018
Results posted
Jul 29, 2019
Last update
Jun 3, 2021

Study contacts

Study Director
study director · Takeda

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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