A Phase 3 Study of KHK4827 in Patients With Systemic Sclerosis

A Phase 3, Placebo-controlled, Double-blind Comparative Study of KHK4827 With an Open-label Extension Period in Subjects With Systemic Sclerosis Who Have Moderate to Severe Skin Thickening

To evaluate the efficacy and safety of KHK4827 in patients with systemic sclerosis who have moderate to severe skin thickening

Study Overview

• Status: Active, not recruiting
• Conditions: Moderate to Severe Systemic Sclerosis
• Intervention / Treatment: Drug: Placebo; Drug: KHK4827

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 457-8510
      • Chukyo Hospital
  • Bunkyo-ku
    • Tokyo, Bunkyo-ku, Japan, 113-8655
      • The University of Tokyo Hospital
  • Fukui
    • Yoshida-gun, Fukui, Japan, 910-1193
      • The University of Fukui Hospital
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 216-8511
      • St. Marianna University School of Medecine Hospital
  • Osaka
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject meets the criteria for diagnosis of the Diagnostic Criteria, Severity Classification, and Clinical Practice Guidelines for Systemic Sclerosis （Japanese Dermatological Association 2016） at the pre-examination
• Subject presented the first symptoms of sclerosis other than Raynaud's phenomenon within 60 months before enrollment
• Subject who has systemic sclerosis accompanied by moderate to severe skin thickening with an mRSS of 10 to <30 at the pre-examination and who has progressing skin thickening

Exclusion Criteria:

1. Any of the following significant concomitant diseases:

   • Type 1 diabetes
   • Poorly controlled type 2 diabetes (HbA1c > 8.5%)
   • Congestive heart failure (Class II to IV of the New York Heart Association Functional Classification)
   • Myocartial infarction, unstable angina, or stroke occurring within 12 months before the first dose of investigational product
   • Poorly controlled hypertension (systolic pressure > 150 mm Hg or diastolic pressure > 90 mg Hg at screening)
   • Severe chronic lung disease (%FVC < 60% and %DLco < 40%, calculated according to the Reference Values for Spirometry, Including Viral Capacity, in Japanese Adults Calcluated with the LMS Method and Compared with Previous Values [Japanese Respiratory Society])
   • Major chronic inflammatory diseases or connective tissue diseases other than scleroderma
2. Patient has a history or evidence of a psychiatric disorder, alcohol and/or substance abuse, or any other mental health disorder that, in the opinion of the investigators, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
3. Patient has a history or evidence of suicidal ideation (severity of 4 or 5) or any suicidal behavior based on an assessment with the Columbia-Suicide Severity Rating Scale (C-SSRS) at enrollment
4. Patient has severe depression based on a total score of ≥ 15 on the Patient Health Questionnaire-8 (PHQ-8) at enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Q2W, SC
EXPERIMENTAL: KHK4827	Drug: KHK4827; 210 mg Q2W, SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in modified Rodnan skin score (mRSS) from baseline at Week 24	mRSS: scored 0(normal), 1(mild), 2(moderate), or 3(severe) per each site, assessed in 17 different body sites, total score=51	at least 2 weeks up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in modified Rodnan skin score (mRSS) from baseline at Week 52	at least 2 weeks up to 52 weeks

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 23, 2019
• Primary Completion (ACTUAL): October 16, 2020
• Study Completion (ANTICIPATED): February 29, 2024

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: May 19, 2019
• First Posted (ACTUAL): May 21, 2019

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 13, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: systemic sclerosis; brodalumab; KHK4827
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Dermatologic Agents; Brodalumab
• Other Study ID Numbers: 4827-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No