Back to resultsA Study of Guselkumab in Participants With Systemic Sclerosis
Primary Purpose
Scleroderma, Systemic
Status
Active
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Guselkumab Dose 1
Guselkumab Dose 2
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Scleroderma, Systemic
Eligibility Criteria
Inclusion criteria:
- Diagnosis of systemic sclerosis (SSc) according to American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) 2013 criteria
- Diffuse cutaneous SSc according to the LeRoy criteria that is, skin fibrosis proximal to the elbows and knees in addition to acral fibrosis
- Disease duration of ≤36 months (defined as time from first non-Raynaud phenomenon manifestation).
- Greater than or equal to (>=) 10 and less than or equal to (<=) 22 modified Rodnan skin score (mRSS) units at screening and Week 0
- Forced vital capacity (FVC) >= 60 percent (%) of predicted at screening
- Diffusing capacity of the lung for carbon monoxide (DLCO) >= 40% of predicted (hemoglobin-corrected) at screening.
- Participants who meet 1 of the following criteria at screening: increase of >=3 mRSS units, compared with an assessment performed within the previous 2 to 6 months; Involvement of 1 new body area with an increase of >=2 mRSS units compared with an assessment performed within the previous 2 to 6 months; and Involvement of 2 new body areas with increase of >=1 mRSS units compared with the assessment within the previous 2 to 6 months
Exclusion Criteria:
- History of liver or renal insufficiency (estimated creatinine clearance below 60 milliliter per minute [mL/min]); significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
- Has any known severe or uncontrolled SSc complications including hemoptysis, pulmonary hemorrhage, renal crisis
- Has an interstitial lung disease requiring oxygen therapy
- Has any rheumatic disease other than SSc such as rheumatoid arthritis (RA), polymyalgia rheumatica (PMR), systemic lupus erythematosus, polymyositis/dermatomyositis that could interfere with assessment of SSc
- Has a current diagnosis or signs or symptoms of severe, progressive, or uncontrolled renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances. (or, in the investigator's opinion, any other concomitant medical condition that places the participant at risk by participating in this study)
Sites / Locations
- Chukyo Hospital
- The University of Tokyo Hospital
- Wakayama Medical University Hospital
- University of Fukui Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Group A: Guselkumab
Group B: Placebo
Arm Description
Participants will receive intravenous (IV) injection of Guselkumab Dose 1 at Week 0, 4, and 8 followed by subcutaneous (SC) injection of Dose 2 Guselkumab every 4 weeks (Q4W) from Week 12 to Week 48 (end of maintenance phase). Participants will receive SC injection of Guselkumab Dose 2 and IV injection of placebo at long-term extension (LTE) Weeks 52, 56, and 60 followed by SC injection of Guselkumab Dose 2 Q4W from LTE Week 64 until Week 100.
Participants will receive IV injection of matching placebo at Week 0, 4, and 8 followed by SC injection of matching placebo Q4W from Week 12 to Week 48 (end of maintenance phase). Participants will receive SC injection of Placebo and IV injection of Guselkumab Dose 1 at LTE Weeks 52, 56, and 60 followed by SC injection of Guselkumab Dose 2 Q4W from LTE Week 64 until Week 100.
Outcomes
Primary Outcome Measures
Change from Baseline in Modified Rodnan Skin Score (mRSS) at Week 24
The mRSS is a validated physical examination method for estimating skin induration. It correlates with biopsy measures of skin thickness and reflects prognosis and visceral involvement, especially in early disease. It is scored on 0 (normal) to 3 (severe induration) ordinal scales over 17 body areas, with a maximum score of 51 and is used to categorize severity of systemic sclerosis (SSc). Higher the score maximum the severity.
Secondary Outcome Measures
Change From Baseline in mRSS at Week 52
The mRSS is a validated physical examination method for estimating skin induration. It correlates with biopsy measures of skin thickness and reflects prognosis and visceral involvement, especially in early disease. It is scored on 0 (normal) to 3 (severe induration) ordinal scales over 17 body areas, with a maximum score of 51 and is used to categorize severity of SSc.
Percentage of Participants with Worsening of mRSS at Week 24 and Week 52
The mRSS is a validated physical examination method for estimating skin induration. It correlates with biopsy measures of skin thickness and reflects prognosis and visceral involvement, especially in early disease. It is scored on 0 (normal) to 3 (severe induration) ordinal scales over 17 body areas, with a maximum score of 51 and is used to categorize severity of SSc.
Percentage of Participants Achieving a Score of 0.6 in American College of Rheumatology Combined Response Index in diffuse cutaneous systemic sclerosis (dcSSc) (ACR CRISS) at Week 24 and Week 52
ACR CRISS is composite response index for clinical trials in early dcSSc developed by an international group of experts in SSc. Application of ACR CRISS algorithm in a randomized clinical trial is a 2-step process. Firstly, participants will be evaluated to have met the criterion for not improved. If yes, these participants are assigned a probability score of 0.0. For the remaining participants, calculate the probability based on change in 5 measures: mRSS, percentage (%) of predicted FVC, HAQ-DI, patient's global assessment, and physician's global assessment, where each measure has a probability score between 0 and 1.
Change from Baseline in Forced Vital Capacity (FVC) at Week 24 and Week 52
Pulmonary function test will be assessed by FVC.
Change from Baseline in Percent (%) Predicted FVC at Week 24 and Week 52
Pulmonary function test will be assessed by % predicted FVC.
Change from Baseline in the Measured Absolute Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) at Week 24 and Week 52
Pulmonary function test will be assessed by measuring absolute DLCO.
Change from Baseline in the Derived % Predicted DLCO at Week 24 and Week 52
Pulmonary function test will be assessed by % predicted DLCO.
Change from Baseline in Digital Ulcer Counts at Week 24 and Week 52
Digital ulcers are defined as a full thickness (greater than [>] 3 millimeters [mm] in maximal diameter) skin lesion with loss of epithelium including lesions covered by eschar. Healing is defined by re epithelialization with loss of pain and exudate.
Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) score at Week 24 and Week 52
The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). Overall score is computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Percentage of Participants with Treatment-emergent Adverse Event (TEAE)
Treatment-emergent AEs are AEs with onset during the treatment phase or that are a consequence of a preexisting condition that has worsened since baseline.
Percentage of Participants with Serious Adverse Event (SAE)
A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important.
Percentage of Participants with Adverse Events of Special Interest (AESI)
Adverse events of special interest that may require expedited reporting or safety evaluation include, but are not limited to: Overdose of a study intervention; suspected abuse/misuse of a study intervention; accidental or occupational exposure to a study intervention; unexpected therapeutic or clinical benefit from use of a study intervention; Medication error, intercepted medication error, or potential medication error involving a Johnson and Johnson medicinal product (with or without patient exposure to the Johnson and Johnson medicinal product, for example, product name confusion, product label confusion, intercepted prescribing or dispensing errors); and exposure to a sponsor study intervention from breastfeeding. Any newly identified malignancy or case of active tuberculosis (TB) or interstitial lung disease (ILD) occurring after the first study intervention administration(s) in participants are considered as AESI.
Serum Concentration of Guselkumab
Serum samples will be analyzed to determine concentrations of guselkumab using a validated, specific, and sensitive method.
Number of Participants with Antibodies of Guselkumab
Number of participants with incidence antibodies of Guselkumab antibody will be assessed.
Full Information
NCT ID
NCT04683029
First Posted
December 22, 2020
Last Updated
October 10, 2023
Sponsor
Janssen Pharmaceutical K.K.
1. Study Identification
Unique Protocol Identification Number
NCT04683029
Brief Title
A Study of Guselkumab in Participants With Systemic Sclerosis
Official Title
A Multicenter, Randomized, Placebo-controlled, Double-blind, Proof-of-concept Study of Guselkumab in Participants With Systemic Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 24, 2021 (Actual)
Primary Completion Date
May 17, 2023 (Actual)
Study Completion Date
July 5, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Pharmaceutical K.K.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of the study is to evaluate the efficacy of guselkumab in participants with systemic sclerosis (SSc).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Scleroderma, Systemic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
56 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A: Guselkumab
Arm Type
Experimental
Arm Description
Participants will receive intravenous (IV) injection of Guselkumab Dose 1 at Week 0, 4, and 8 followed by subcutaneous (SC) injection of Dose 2 Guselkumab every 4 weeks (Q4W) from Week 12 to Week 48 (end of maintenance phase). Participants will receive SC injection of Guselkumab Dose 2 and IV injection of placebo at long-term extension (LTE) Weeks 52, 56, and 60 followed by SC injection of Guselkumab Dose 2 Q4W from LTE Week 64 until Week 100.
Arm Title
Group B: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive IV injection of matching placebo at Week 0, 4, and 8 followed by SC injection of matching placebo Q4W from Week 12 to Week 48 (end of maintenance phase). Participants will receive SC injection of Placebo and IV injection of Guselkumab Dose 1 at LTE Weeks 52, 56, and 60 followed by SC injection of Guselkumab Dose 2 Q4W from LTE Week 64 until Week 100.
Intervention Type
Drug
Intervention Name(s)
Guselkumab Dose 1
Intervention Description
Guselkumab Dose 1 will be administered intravenously.
Intervention Type
Drug
Intervention Name(s)
Guselkumab Dose 2
Intervention Description
Guselkumab Dose 2 will be administered subcutaneously.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be administered intravenously or subcutaneously.
Primary Outcome Measure Information:
Title
Change from Baseline in Modified Rodnan Skin Score (mRSS) at Week 24
Description
The mRSS is a validated physical examination method for estimating skin induration. It correlates with biopsy measures of skin thickness and reflects prognosis and visceral involvement, especially in early disease. It is scored on 0 (normal) to 3 (severe induration) ordinal scales over 17 body areas, with a maximum score of 51 and is used to categorize severity of systemic sclerosis (SSc). Higher the score maximum the severity.
Time Frame
Baseline and Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline in mRSS at Week 52
Description
The mRSS is a validated physical examination method for estimating skin induration. It correlates with biopsy measures of skin thickness and reflects prognosis and visceral involvement, especially in early disease. It is scored on 0 (normal) to 3 (severe induration) ordinal scales over 17 body areas, with a maximum score of 51 and is used to categorize severity of SSc.
Time Frame
Baseline and Week 52
Title
Percentage of Participants with Worsening of mRSS at Week 24 and Week 52
Description
The mRSS is a validated physical examination method for estimating skin induration. It correlates with biopsy measures of skin thickness and reflects prognosis and visceral involvement, especially in early disease. It is scored on 0 (normal) to 3 (severe induration) ordinal scales over 17 body areas, with a maximum score of 51 and is used to categorize severity of SSc.
Time Frame
At Week 24 and Week 52
Title
Percentage of Participants Achieving a Score of 0.6 in American College of Rheumatology Combined Response Index in diffuse cutaneous systemic sclerosis (dcSSc) (ACR CRISS) at Week 24 and Week 52
Description
ACR CRISS is composite response index for clinical trials in early dcSSc developed by an international group of experts in SSc. Application of ACR CRISS algorithm in a randomized clinical trial is a 2-step process. Firstly, participants will be evaluated to have met the criterion for not improved. If yes, these participants are assigned a probability score of 0.0. For the remaining participants, calculate the probability based on change in 5 measures: mRSS, percentage (%) of predicted FVC, HAQ-DI, patient's global assessment, and physician's global assessment, where each measure has a probability score between 0 and 1.
Time Frame
At Week 24 and Week 52
Title
Change from Baseline in Forced Vital Capacity (FVC) at Week 24 and Week 52
Description
Pulmonary function test will be assessed by FVC.
Time Frame
Baseline, Week 24, and Week 52
Title
Change from Baseline in Percent (%) Predicted FVC at Week 24 and Week 52
Description
Pulmonary function test will be assessed by % predicted FVC.
Time Frame
Baseline, Week 24 and Week 52
Title
Change from Baseline in the Measured Absolute Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) at Week 24 and Week 52
Description
Pulmonary function test will be assessed by measuring absolute DLCO.
Time Frame
Baseline, Week 24 and Week 52
Title
Change from Baseline in the Derived % Predicted DLCO at Week 24 and Week 52
Description
Pulmonary function test will be assessed by % predicted DLCO.
Time Frame
Baseline, Week 24 and Week 52
Title
Change from Baseline in Digital Ulcer Counts at Week 24 and Week 52
Description
Digital ulcers are defined as a full thickness (greater than [>] 3 millimeters [mm] in maximal diameter) skin lesion with loss of epithelium including lesions covered by eschar. Healing is defined by re epithelialization with loss of pain and exudate.
Time Frame
Baseline, Week 24, and Week 52
Title
Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) score at Week 24 and Week 52
Description
The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). Overall score is computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Time Frame
Baseline, Week 24 and Week 52
Title
Percentage of Participants with Treatment-emergent Adverse Event (TEAE)
Description
Treatment-emergent AEs are AEs with onset during the treatment phase or that are a consequence of a preexisting condition that has worsened since baseline.
Time Frame
From baseline up to Week 24, Week 52, Week 76 and Week 104
Title
Percentage of Participants with Serious Adverse Event (SAE)
Description
A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important.
Time Frame
From baseline up to Week 24, Week 52, Week 76 and Week 104
Title
Percentage of Participants with Adverse Events of Special Interest (AESI)
Description
Adverse events of special interest that may require expedited reporting or safety evaluation include, but are not limited to: Overdose of a study intervention; suspected abuse/misuse of a study intervention; accidental or occupational exposure to a study intervention; unexpected therapeutic or clinical benefit from use of a study intervention; Medication error, intercepted medication error, or potential medication error involving a Johnson and Johnson medicinal product (with or without patient exposure to the Johnson and Johnson medicinal product, for example, product name confusion, product label confusion, intercepted prescribing or dispensing errors); and exposure to a sponsor study intervention from breastfeeding. Any newly identified malignancy or case of active tuberculosis (TB) or interstitial lung disease (ILD) occurring after the first study intervention administration(s) in participants are considered as AESI.
Time Frame
From baseline up to Week 24, Week 52, Week 76 and Week 104
Title
Serum Concentration of Guselkumab
Description
Serum samples will be analyzed to determine concentrations of guselkumab using a validated, specific, and sensitive method.
Time Frame
Up to 112 Weeks (End of study [EOS]/early termination [ET])
Title
Number of Participants with Antibodies of Guselkumab
Description
Number of participants with incidence antibodies of Guselkumab antibody will be assessed.
Time Frame
Up to 112 Weeks (EOS/ET)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Diagnosis of systemic sclerosis (SSc) according to American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) 2013 criteria
Diffuse cutaneous SSc according to the LeRoy criteria that is, skin fibrosis proximal to the elbows and knees in addition to acral fibrosis
Disease duration of ≤36 months (defined as time from first non-Raynaud phenomenon manifestation).
Greater than or equal to (>=) 10 and less than or equal to (<=) 22 modified Rodnan skin score (mRSS) units at screening and Week 0
Forced vital capacity (FVC) >= 60 percent (%) of predicted at screening
Diffusing capacity of the lung for carbon monoxide (DLCO) >= 40% of predicted (hemoglobin-corrected) at screening.
Participants who meet 1 of the following criteria at screening: increase of >=3 mRSS units, compared with an assessment performed within the previous 2 to 6 months; Involvement of 1 new body area with an increase of >=2 mRSS units compared with an assessment performed within the previous 2 to 6 months; and Involvement of 2 new body areas with increase of >=1 mRSS units compared with the assessment within the previous 2 to 6 months
Exclusion Criteria:
History of liver or renal insufficiency (estimated creatinine clearance below 60 milliliter per minute [mL/min]); significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
Has any known severe or uncontrolled SSc complications including hemoptysis, pulmonary hemorrhage, renal crisis
Has an interstitial lung disease requiring oxygen therapy
Has any rheumatic disease other than SSc such as rheumatoid arthritis (RA), polymyalgia rheumatica (PMR), systemic lupus erythematosus, polymyositis/dermatomyositis that could interfere with assessment of SSc
Has a current diagnosis or signs or symptoms of severe, progressive, or uncontrolled renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances. (or, in the investigator's opinion, any other concomitant medical condition that places the participant at risk by participating in this study)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Pharmaceutical K.K., Japan Clinical Trial
Organizational Affiliation
Janssen Pharmaceutical K.K.
Official's Role
Study Director
Facility Information:
Facility Name
Chukyo Hospital
City
Aichi
ZIP/Postal Code
457-8510
Country
Japan
Facility Name
The University of Tokyo Hospital
City
Tokyo
ZIP/Postal Code
113-8655
Country
Japan
Facility Name
Wakayama Medical University Hospital
City
Wakayama
ZIP/Postal Code
641-8510
Country
Japan
Facility Name
University of Fukui Hospital
City
Yoshida
ZIP/Postal Code
910-1193
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency
Learn more about this trial
A Study of Guselkumab in Participants With Systemic Sclerosis
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