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

Primary Purpose

Atopic Dermatitis

Status

Terminated

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

DS-2741a

Placebo

About this trial

This is an interventional treatment trial for Atopic Dermatitis focused on measuring Atopic Dermatitis, DS-2741a

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Osaka Pharmacology Clinical Research Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Part 1: DS-2741a Cohort 1, 5 mg

Part 1: DS-2741a Cohort 2, 15 mg

Part 1: DS-2741a Cohort 3, 50 mg

Part 1: DS-2741a Cohort 4, 150 mg

Part 1: DS-2741a Cohort 5, 500 mg

Part 1: DS-2741a Cohort 6, 1000 mg

Part 1: Placebo

Part 2: DS-2741a Cohort 1, X mg (based on results of Part 1)

Part 2: DS-2741a Cohort 1, Y mg (based on results of Part 1)

Part 3: DS-2741a Cohort 1, Z mg (based on results of Part 1)

Part 3: Placebo

Arm Description

Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 5 mg.

Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 15 mg.

Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 50 mg.

Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 150 mg.

Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 500 mg.

Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 1000 mg.

Participants will be randomized to receive a single, subcutaneous injection of placebo.

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.

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.

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.

Participants will be randomized to receive a single, subcutaneous injection of placebo.

Outcomes

Primary Outcome Measures

Incidence of adverse events among participants receiving DS-2741a (Part 1 and Part 3)

Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 2)

Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 2)

Characterize pharmacokinetic parameter area under the curve from time 0 to last measurable time point (AUClast) of plasma DS-2741a (Part 2)

Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 2)

Characterize pharmacokinetic parameter total clearance (CL/F) of plasma DS-2741a (Part 2)

Characterize pharmacokinetic parameter area under the curve from time 0 to infinity (AUCinf) of plasma DS-2741a (Part 2)

Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 2)

Characterize pharmacokinetic parameter volume of distribution (Vz/F) of plasma DS-2741a (Part 2)

Secondary Outcome Measures

Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 1)

Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 1)

Characterize pharmacokinetic parameter area under the curve from time 0 to last measurable time point (AUClast) of plasma DS-2741a (Part 1)

Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 1)

Characterize pharmacokinetic parameter total clearance (CL/F) of plasma DS-2741a (Part 1)

Characterize pharmacokinetic parameter area under the curve from time 0 to infinity (AUCinf) of plasma DS-2741a (Part 1)

Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 1)

Characterize pharmacokinetic parameter volume of distribution (Vz/F) of plasma DS-2741a (Part 1)

Incidence of anti-drug antibodies (ADAs) against DS-2741a (Part 1 and Part 2)

Incidence of adverse events among participants receiving DS-2741a (Part 2)

Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 3)

Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 3)

Characterize pharmacokinetic parameter trough plasma concentration (Ctrough) of plasma DS-2741a (Part 3)

Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 3)

Characterize pharmacokinetic parameter area under the curve from time 0 to tau (504-672 h) (AUCtau) of plasma DS-2741a (Part 3)

Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 3)

Incidence of anti-drug antibodies (ADAs) against DS-2741a (Part 3)

Full Information

NCT ID

NCT04211415

First Posted

December 23, 2019

Last Updated

June 16, 2021

Sponsor

Daiichi Sankyo Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT04211415

Brief Title

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

Official Title

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.

Study Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Terminated

Why Stopped

Company decision of termination of the clinical program.

Study Start Date

January 13, 2020 (Actual)

Primary Completion Date

March 14, 2020 (Actual)

Study Completion Date

December 18, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Daiichi Sankyo Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Atopic Dermatitis

Keywords

Atopic Dermatitis, DS-2741a

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

The participant, care provider, investigator, and outcomes assessor will be blinded in Part 1 and Part 3 of the study. Part 2 of the study will be unblinded.

Allocation

Randomized

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: DS-2741a Cohort 1, 5 mg

Arm Type

Experimental

Arm Description

Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 5 mg.

Arm Title

Part 1: DS-2741a Cohort 2, 15 mg

Arm Type

Experimental

Arm Description

Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 15 mg.

Arm Title

Part 1: DS-2741a Cohort 3, 50 mg

Arm Type

Experimental

Arm Description

Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 50 mg.

Arm Title

Part 1: DS-2741a Cohort 4, 150 mg

Arm Type

Experimental

Arm Description

Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 150 mg.

Arm Title

Part 1: DS-2741a Cohort 5, 500 mg

Arm Type

Experimental

Arm Description

Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 500 mg.

Arm Title

Part 1: DS-2741a Cohort 6, 1000 mg

Arm Type

Experimental

Arm Description

Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 1000 mg.

Arm Title

Part 1: Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will be randomized to receive a single, subcutaneous injection of placebo.

Arm Title

Part 2: DS-2741a Cohort 1, X mg (based on results of Part 1)

Arm Type

Experimental

Arm Description

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.

Arm Title

Part 2: DS-2741a Cohort 1, Y mg (based on results of Part 1)

Arm Type

Experimental

Arm Description

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.

Arm Title

Part 3: DS-2741a Cohort 1, Z mg (based on results of Part 1)

Arm Type

Experimental

Arm Description

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.

Arm Title

Part 3: Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will be randomized to receive a single, subcutaneous injection of placebo.

Intervention Type

Drug

Intervention Name(s)

DS-2741a

Intervention Description

Single, subcutaneous injection (upper arm, upper part of the thigh, or abdominal wall in principle) administered weekly for 4 weeks

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Single, subcutaneous injection administered weekly for 4 weeks

Primary Outcome Measure Information:

Title

Incidence of adverse events among participants receiving DS-2741a (Part 1 and Part 3)

Time Frame

Day 1 through end of study, up to 4 weeks

Title

Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 2)

Time Frame

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

Title

Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 2)

Time Frame

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

Title

Characterize pharmacokinetic parameter area under the curve from time 0 to last measurable time point (AUClast) of plasma DS-2741a (Part 2)

Time Frame

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

Title

Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 2)

Time Frame

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

Title

Characterize pharmacokinetic parameter total clearance (CL/F) of plasma DS-2741a (Part 2)

Time Frame

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

Title

Characterize pharmacokinetic parameter area under the curve from time 0 to infinity (AUCinf) of plasma DS-2741a (Part 2)

Time Frame

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

Title

Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 2)

Time Frame

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

Title

Characterize pharmacokinetic parameter volume of distribution (Vz/F) of plasma DS-2741a (Part 2)

Time Frame

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 Measure Information:

Title

Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 1)

Time Frame

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

Title

Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 1)

Time Frame

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

Title

Characterize pharmacokinetic parameter area under the curve from time 0 to last measurable time point (AUClast) of plasma DS-2741a (Part 1)

Time Frame

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

Title

Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 1)

Time Frame

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

Title

Characterize pharmacokinetic parameter total clearance (CL/F) of plasma DS-2741a (Part 1)

Time Frame

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

Title

Characterize pharmacokinetic parameter area under the curve from time 0 to infinity (AUCinf) of plasma DS-2741a (Part 1)

Time Frame

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

Title

Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 1)

Time Frame

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

Title

Characterize pharmacokinetic parameter volume of distribution (Vz/F) of plasma DS-2741a (Part 1)

Time Frame

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

Title

Incidence of anti-drug antibodies (ADAs) against DS-2741a (Part 1 and Part 2)

Time Frame

Day 1 (pre-dose), Day 28, Day 49

Title

Incidence of adverse events among participants receiving DS-2741a (Part 2)

Time Frame

Day 1 through end of study, up to 4 weeks

Title

Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 3)

Time Frame

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

Title

Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 3)

Time Frame

Title

Characterize pharmacokinetic parameter trough plasma concentration (Ctrough) of plasma DS-2741a (Part 3)

Time Frame

Title

Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 3)

Time Frame

Title

Characterize pharmacokinetic parameter area under the curve from time 0 to tau (504-672 h) (AUCtau) of plasma DS-2741a (Part 3)

Time Frame

Title

Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 3)

Time Frame

Title

Incidence of anti-drug antibodies (ADAs) against DS-2741a (Part 3)

Time Frame

Day 1 (pre-dose),Day 7 (pre-dose), Day 14 (pre-dose), Day 21 (pre-dose), Day 49, Day 63

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Study Leader

Organizational Affiliation

Daiichi Sankyo, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Osaka Pharmacology Clinical Research Hospital

City

Osaka

Country

Japan

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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 URL

https://www.vivli.org/ourmember/daiichi-sankyo/

Learn more about this trial

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

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