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DS-6016a Phase I Study
- Single ascending dose study to assess the safety, tolerability, and pharmacokinetics of DS-6016a after subcutaneous injection in healthy Japanese subjects. -

DS-6016a Phase I Study
- Single ascending dose study to assess the safety, tolerability, and pharmacokinetics of DS-6016a after subcutaneous injection in healthy Japanese subjects. -

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- In the safety analysis set, the mean (range) age of the subjects was 28.2 (20 to 41) years, the mean weight was 63.75 kg, and the mean BMI was 21.53 kg/m^2. - No notable differences were found in the demographic or other baseline characteristics among the administration groups. - The demographic and other baseline characteristics of the PK analysis set were similar to those of the safety analysis set.

- In each cohort (Cohorts 1 to 6), 2 subjects were randomized to placebo and 6 subjects were randomized to DS-6016a (5 mg for Cohort 1 [5-mg group], 15 mg for Cohort 2 [15-mg group], 50 mg for Cohort 3 [50-mg group], 150 mg for Cohort 4 [150-mg group], 500 mg for Cohort 5 [500-mg group], and 1000 mg for Cohort 6 [1000-mg group]). - All 48 randomized subjects were included in the safety analysis set, and the ADA and anti-HCP antibody analysis set. - Of the 48 randomized subjects, 36 subjects who received DS-6016a were included in the PK analysis set.

- The incidence of TEAEs was 66.7% (8 of 12) in the placebo group and 44.4% (16 of 36) in the all DS-6016a group. - The incidence of TEAEs in each DS-6016a group was 33.3% (2 of 6) in the 5-mg group, 50.0% (3 of 6) in the 15-mg group, 50.0% (3 of 6) in the 50-mg group, 33.3% (2 of 6) in the 150-mg group, 66.7% (4 of 6) in the 500-mg group, and 33.3% (2 of 6) in the 1000-mg group. - The TEAEs reported by 20% or more of the subjects in any treatment group were vaccination site pain, C-reactive protein increased , alanine aminotransferase increased, blood creatine phosphokinase increased. - All TEAEs were mild, and resolved without treatment except for 2 moderate events (dental caries and tonsillitis). - The incidence of TEAEs related to the study drug was 16.7% (2 of 12) in the placebo group and 11.1% (4 of 36) in the all DS-6016a group. - The incidence of TEAEs related to the study drug in each DS-6016a group was 0.0% (0 of 6) in the 5-mg group, 16.7% (1 of 6) in the 15-mg group, 0.0% (0 of 6) in the 50-mg group, 16.7% (1 of 6) in the 150-mg group, 33.3% (2 of 6) in the 500-mg group, and 0.0% (0 of 6) in the 1000-mg group. - The reported TEAEs related to the study drug were headache (1 subject in the 15-mg group), nausea (1 subject in the 15-mg group), rash (1 subject in the 150-mg group), alanine aminotransferase increased (1 subject in the placebo group and 2 subjects in the 500-mg group), aspartate aminotransferase increased (1 subject in the placebo group), and gamma glutamyltransferase increased (1 subject in the placebo group). All TEAEs related to the study drug were mild and resolved without treatment. - No deaths, SAEs, TEAEs leading to study discontinuation, or severe TEAEs were reported in this study. - No notable trends or differences among the treatment groups were found in any of the laboratory parameters, vital signs, 12-lead ECG, body weight, or other safety endpoints.

<Primary outcome> Safety: See "Adverse events" <Secondary outcome> Pharmacokinetics: - After subcutaneous administration, DS-6016a was absorbed slowly, with the median Tmax ranging from 144.00 to 240.00 h, and the plasma concentration of DS-6016a decreased slowly after reaching Cmax, with the mean t1/2 ranging from 391 to 844 h, across a dose level range of 5 to 1000 mg. - The median Tmax and mean t1/2 tended to increase with the dose across a dose level range of 5 to 1000 mg. - The DS-6016a systemic exposure (Cmax, AUCinf and AUClast) increased in a dose dependent manner. - The exposure tended to increase in a greater-than-dose-proportional manner across the entire dose level range of 5 to 1000 mg, and the increases tended to be linear at dose levels of 150 mg and above. Formation of anti-drug antibody and anti-host cell protein antibody: - No subjects were positive for ADA at baseline. - After administration of the study drug, treatment-induced ADA was reported in 4 of 36 subjects (11.1%) who received DS-6016a. - The dose-dependency in the incidence of ADA was not observed. - In each dose group, the DS-6016a systemic exposure of the subjects with ADA-positive results tended to be lower than that of the subjects with ADA-negative results. - No subjects were positive for anti-HCP antibody at baseline or any post-baseline time point.

- DS-6016a was shown to have an acceptable safety and tolerability profile at single subcutaneous doses of 5, 15, 50, 150, 500 and 1000 mg in healthy Japanese male adults. -The incidence of TEAEs was 66.7% in placebo group and 44.4% in DS-6016a group. -All TEAEs in DS-6016a group were mild except for 2 moderate events. -The DS-6016a systemic exposure tended to increase in a greater than-dose-proportional manner across the doses of 5 to 1000 mg, and the increase tended to be linear at 150 mg and above.

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https://jrct.niph.go.jp/latest-detail/jRCT2051200155

Inoguchi Akihiro

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

dsclinicaltrial@daiichisankyo.co.jp

Contact for Clinical Trial Information

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Complete

Mar. 20, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1. Japanese healthy male subjects.
2. Age >=20 and <=45 years upon providing informed consent.
3. Body mass index (BMI) >=18.5 and <25.0 kg/m2 at screening.

1. Having a history of hypersensitivity to any drugs or substances, or being idiosyncratic (eg, having penicillin allergy)
2. Having alcohol or drug dependence etc.

Male

Fibrodysplasia ossificans progressiva

DS-6016a or Placebo is administered at a single subcutaneous injection into the upper arm, upper part of the thigh, or abdominal wall.

Safety:
Adverse Events, laboratory data, body weight, vital signs, and 12-lead Electrocardiography

-Plasma pharmacokinetics parameters for DS-6016a
-Formation of anti-drug antibody and anti-host cell protein antibody

+81-6-6395-9000

Mar. 19, 2021

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