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

Atopic Dermatitis Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04211415
• Other study ID #: DS2741-A-J101
• Secondary ID: 195071
• Status: Terminated
• Phase: Phase 1
• Start date: January 13, 2020
• Est. completion date: December 18, 2020

Study information

• Verified date: June 2021
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: December 18, 2020
• Est. primary completion date: March 14, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• DS-2741a
Single, subcutaneous injection (upper arm, upper part of the thigh, or abdominal wall in principle) administered weekly for 4 weeks
• Placebo
Single, subcutaneous injection administered weekly for 4 weeks

Locations

Country	Name	City	State
Japan	Osaka Pharmacology Clinical Research Hospital	Osaka

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events among participants receiving DS-2741a (Part 1 and Part 3)		Day 1 through end of study, up to 4 weeks
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Incidence of anti-drug antibodies (ADAs) against DS-2741a (Part 1 and Part 2)		Day 1 (pre-dose), Day 28, Day 49
Secondary	Incidence of adverse events among participants receiving DS-2741a (Part 2)		Day 1 through end of study, up to 4 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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