Clinical trial NCT04211415: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Atopic Dermatitis
Keywords: Atopic Dermatitis
DS-2741a
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2019-12-26
Enrollment: 8
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of adverse events among participants receiving DS-2741a (Part 1 and Part 3)
timeFrame: Day 1 through end of study, up to 4 weeks
measure: Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 2)
timeFrame: 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
measure: Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 2)
timeFrame: 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
measure: Characterize pharmacokinetic parameter area under the curve from time 0 to last measurable time point (AUClast) of plasma DS-2741a (Part 2)
timeFrame: 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
measure: Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 2)
timeFrame: 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
measure: Characterize pharmacokinetic parameter total clearance (CL/F) of plasma DS-2741a (Part 2)
timeFrame: 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
measure: Characterize pharmacokinetic parameter area under the curve from time 0 to infinity (AUCinf) of plasma DS-2741a (Part 2)
timeFrame: 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
measure: Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 2)
timeFrame: 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
measure: Characterize pharmacokinetic parameter volume of distribution (Vz/F) of plasma DS-2741a (Part 2)
timeFrame: 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 outcomes:
measure: Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 1)
timeFrame: 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
measure: Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 1)
timeFrame: 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
measure: Characterize pharmacokinetic parameter area under the curve from time 0 to last measurable time point (AUClast) of plasma DS-2741a (Part 1)
timeFrame: 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
measure: Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 1)
timeFrame: 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
measure: Characterize pharmacokinetic parameter total clearance (CL/F) of plasma DS-2741a (Part 1)
timeFrame: 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
measure: Characterize pharmacokinetic parameter area under the curve from time 0 to infinity (AUCinf) of plasma DS-2741a (Part 1)
timeFrame: 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
measure: Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 1)
timeFrame: 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
measure: Characterize pharmacokinetic parameter volume of distribution (Vz/F) of plasma DS-2741a (Part 1)
timeFrame: 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
measure: Incidence of anti-drug antibodies (ADAs) against DS-2741a (Part 1 and Part 2)
timeFrame: Day 1 (pre-dose), Day 28, Day 49
measure: Incidence of adverse events among participants receiving DS-2741a (Part 2)
timeFrame: Day 1 through end of study, up to 4 weeks
measure: Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 3)
timeFrame: 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
measure: Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 3)
timeFrame: 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
measure: Characterize pharmacokinetic parameter trough plasma concentration (Ctrough) of plasma DS-2741a (Part 3)
timeFrame: 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
measure: Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 3)
timeFrame: 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
measure: Characterize pharmacokinetic parameter area under the curve from time 0 to tau (504-672 h) (AUCtau) of plasma DS-2741a (Part 3)
timeFrame: 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
measure: Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 3)
timeFrame: 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
measure: Incidence of anti-drug antibodies (ADAs) against DS-2741a (Part 3)
timeFrame: Day 1 (pre-dose),Day 7 (pre-dose), Day 14 (pre-dose), Day 21 (pre-dose), Day 49, Day 63
Other outcomes:
Locations:
city: Osaka
country: Japan
facility: Osaka Pharmacology Clinical Research Hospital
Study officials:
affiliation: Daiichi Sankyo
name: Clinical Study Leader
role: STUDY_DIRECTOR
References: