Phase I Study of DS-2741a in Healthy Volunteers and Participants With Atopic Dermatitis

DS-2741a Phase I Study- A Three-part First-in-human Study: Single Ascending Dose and Multiple Dose Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of DS-2741a After Subcutaneous Injection in Healthy Japanese Male Subjects, and Single Dose Study to Assess the Pharmacokinetics, Safety, Pharmacodynamics and Efficacy of DS-2741a After Subcutaneous Injection in Japanese Subjects With Moderate to Severe Atopic Dermatitis.

This is a phase 1, single-center, first-in-human study to assess the safety, pharmacokinetics and pharmacodynamics of DS-2741a after subcutaneous injection in healthy Japanese male volunteers and Japanese participants with moderate to severe atopic dermatitis.

Study Overview

• Status: Terminated
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: DS-2741a; Drug: Placebo

Detailed Description

This study consists of three parts. Part 1 and Part 3 are a single ascending and multiple dose study to assess the safety, pharmacokinetics and pharmacodynamics of DS-2741a after subcutaneous injection in healthy Japanese male participants. Part 2 is a single-dose study to assess the pharmacokinetics, safety, pharmacodynamics and efficacy of DS-2741a after subcutaneous injection in Japanese participants with moderate to severe atopic dermatitis.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan
    • Osaka Pharmacology Clinical Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For Part 1 and Part 3:

  • Japanese healthy male subjects.
  • Age ≥20 and ≤45 years upon providing informed consent.
  • Body mass index (BMI) ≥18.5 and <25.0 kg/m^2 at screening.

• For Part 2:

  • Japanese Male or female, Age ≥20 upon providing informed consent.
  • Diagnosed with chronic atopic dermatitis (AD) at least 3 years before screening and by the criteria of Hannifin and Rajka at screening.

Exclusion Criteria:

• For Part 1 and Part 3:

  • Having a history of atopic dermatitis
  • Having a history of hypersensitivity to drugs or other substances or being idiosyncratic
  • Having alcohol or drug dependence, etc.

• For Part 2:

  • Having an active dermatological disease other than AD, which, in the investigator's opinion, would affect study assessments.
  • Having a history of serious disease in the study potentially endangering the participant, as judged by the investigator or sub-investigator.
  • Having a chronic or acute infection requiring treatment within 28 days before screening.
  • Having superficial skin infections within 7 days before screening.
  • Having a history of recurrent oral herpes and recurrent genital herpes.
  • Having a history of parasitic infection or invasive, opportunistic infection such as histoplasmosis despite infection resolution, etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part 1: DS-2741a Cohort 1, 5 mg; Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 5 mg.	Drug: DS-2741a; Single, subcutaneous injection (upper arm, upper part of the thigh, or abdominal wall in principle) administered weekly for 4 weeks
EXPERIMENTAL: Part 1: DS-2741a Cohort 2, 15 mg; Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 15 mg.	Drug: DS-2741a; Single, subcutaneous injection (upper arm, upper part of the thigh, or abdominal wall in principle) administered weekly for 4 weeks
EXPERIMENTAL: Part 1: DS-2741a Cohort 3, 50 mg; Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 50 mg.	Drug: DS-2741a; Single, subcutaneous injection (upper arm, upper part of the thigh, or abdominal wall in principle) administered weekly for 4 weeks
EXPERIMENTAL: Part 1: DS-2741a Cohort 4, 150 mg; Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 150 mg.	Drug: DS-2741a; Single, subcutaneous injection (upper arm, upper part of the thigh, or abdominal wall in principle) administered weekly for 4 weeks
EXPERIMENTAL: Part 1: DS-2741a Cohort 5, 500 mg; Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 500 mg.	Drug: DS-2741a; Single, subcutaneous injection (upper arm, upper part of the thigh, or abdominal wall in principle) administered weekly for 4 weeks
EXPERIMENTAL: Part 1: DS-2741a Cohort 6, 1000 mg; Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 1000 mg.	Drug: DS-2741a; Single, subcutaneous injection (upper arm, upper part of the thigh, or abdominal wall in principle) administered weekly for 4 weeks
PLACEBO_COMPARATOR: Part 1: Placebo; Participants will be randomized to receive a single, subcutaneous injection of placebo.	Drug: Placebo; Single, subcutaneous injection administered weekly for 4 weeks
EXPERIMENTAL: Part 2: DS-2741a Cohort 1, X mg (based on results of Part 1); Participants will receive a single, subcutaneous injection of DS-2741a X mg, where X mg will be based on the maximum tolerated dose identified in Part 1.	Drug: DS-2741a; Single, subcutaneous injection (upper arm, upper part of the thigh, or abdominal wall in principle) administered weekly for 4 weeks
EXPERIMENTAL: Part 2: DS-2741a Cohort 1, Y mg (based on results of Part 1); Participants will receive a single, subcutaneous injection of DS-2741a Y mg, where Y mg will be based on the maximum tolerated dose identified in Part 1.	Drug: DS-2741a; Single, subcutaneous injection (upper arm, upper part of the thigh, or abdominal wall in principle) administered weekly for 4 weeks
EXPERIMENTAL: Part 3: DS-2741a Cohort 1, Z mg (based on results of Part 1); Participants will be randomized to receive a receive a single, subcutaneous injection of DS-2741a Z mg, where Z mg will be based on the maximum tolerated dose identified in Part 1.	Drug: DS-2741a; Single, subcutaneous injection (upper arm, upper part of the thigh, or abdominal wall in principle) administered weekly for 4 weeks
PLACEBO_COMPARATOR: Part 3: Placebo; Participants will be randomized to receive a single, subcutaneous injection of placebo.	Drug: Placebo; Single, subcutaneous injection administered weekly for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events among participants receiving DS-2741a (Part 1 and Part 3)	Day 1 through end of study, up to 4 weeks
Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 2)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 2)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter area under the curve from time 0 to last measurable time point (AUClast) of plasma DS-2741a (Part 2)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 2)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter total clearance (CL/F) of plasma DS-2741a (Part 2)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter area under the curve from time 0 to infinity (AUCinf) of plasma DS-2741a (Part 2)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 2)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter volume of distribution (Vz/F) of plasma DS-2741a (Part 2)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49

Secondary Outcome Measures

Outcome Measure	Time Frame
Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 1)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 1)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter area under the curve from time 0 to last measurable time point (AUClast) of plasma DS-2741a (Part 1)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 1)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter total clearance (CL/F) of plasma DS-2741a (Part 1)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter area under the curve from time 0 to infinity (AUCinf) of plasma DS-2741a (Part 1)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4,Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 1)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter volume of distribution (Vz/F) of plasma DS-2741a (Part 1)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Incidence of anti-drug antibodies (ADAs) against DS-2741a (Part 1 and Part 2)	Day 1 (pre-dose), Day 28, Day 49
Incidence of adverse events among participants receiving DS-2741a (Part 2)	Day 1 through end of study, up to 4 weeks
Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 3)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 3, Day 5, Day 7 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 10, Day 12, Day 14 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 17
Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 3)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 3, Day 5, Day 7 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 10, Day 12, Day 14 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 17
Characterize pharmacokinetic parameter trough plasma concentration (Ctrough) of plasma DS-2741a (Part 3)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 3, Day 5, Day 7 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 10, Day 12, Day 14 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 17
Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 3)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 3, Day 5, Day 7 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 10, Day 12, Day 14 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 17
Characterize pharmacokinetic parameter area under the curve from time 0 to tau (504-672 h) (AUCtau) of plasma DS-2741a (Part 3)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 3, Day 5, Day 7 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 10, Day 12, Day 14 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 17
Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 3)	Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 3, Day 5, Day 7 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 10, Day 12, Day 14 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 17
Incidence of anti-drug antibodies (ADAs) against DS-2741a (Part 3)	Day 1 (pre-dose),Day 7 (pre-dose), Day 14 (pre-dose), Day 21 (pre-dose), Day 49, Day 63

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 13, 2020
• Primary Completion (ACTUAL): March 14, 2020
• Study Completion (ACTUAL): December 18, 2020

Study Registration Dates

• First Submitted: December 23, 2019
• First Submitted That Met QC Criteria: December 23, 2019
• First Posted (ACTUAL): December 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 22, 2021
• Last Update Submitted That Met QC Criteria: June 16, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Atopic Dermatitis; DS-2741a
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: DS2741-A-J101; 195071 (OTHER: JapicCTI ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No