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

Sponsor
Daiichi Sankyo Co., Ltd. (Industry)
Overall Status
Terminated
CT.gov ID
NCT04211415
Collaborator
(none)
8
Enrollment
1
Location
11
Arms
11.2
Actual Duration (Months)
0.7
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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 Design

Study Type:
Interventional
Actual Enrollment :
8 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes 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.
Primary Purpose:
Treatment
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.
Actual Study Start Date :
Jan 13, 2020
Actual Primary Completion Date :
Mar 14, 2020
Actual Study Completion Date :
Dec 18, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Incidence of adverse events among participants receiving DS-2741a (Part 1 and Part 3) [Day 1 through end of study, up to 4 weeks]

  2. 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]

  3. 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]

  4. 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]

  5. 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]

  6. 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]

  7. 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]

  8. 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]

  9. 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

  1. 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]

  2. 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]

  3. 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]

  4. 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]

  5. 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]

  6. 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]

  7. 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]

  8. 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]

  9. Incidence of anti-drug antibodies (ADAs) against DS-2741a (Part 1 and Part 2) [Day 1 (pre-dose), Day 28, Day 49]

  10. Incidence of adverse events among participants receiving DS-2741a (Part 2) [Day 1 through end of study, up to 4 weeks]

  11. 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]

  12. 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]

  13. 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]

  14. 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]

  15. 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]

  16. 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]

  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]

Eligibility Criteria

Criteria

Ages Eligible for Study:
20 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Osaka Pharmacology Clinical Research Hospital Osaka Japan

Sponsors and Collaborators

  • Daiichi Sankyo Co., Ltd.

Investigators

  • Study Director: Clinical Study Leader, Daiichi Sankyo, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier:
NCT04211415
Other Study ID Numbers:
  • DS2741-A-J101
  • 195071
First Posted:
Dec 26, 2019
Last Update Posted:
Jun 22, 2021
Last Verified:
Jun 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Daiichi Sankyo Co., Ltd.
Atopic Dermatitis
DS-2741a
Additional relevant MeSH terms:
Dermatitis, Atopic
Dermatitis
Eczema

Study Results

No Results Posted as of Jun 22, 2021