A Study of Guselkumab in Participants With Systemic Sclerosis

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy of guselkumab in participants with systemic sclerosis (SSc).

Official Title
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A Multicenter, Randomized, Placebo-controlled, Double-blind, Proof-of-concept Study of Guselkumab in Participants With Systemic Sclerosis

Conditions
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Scleroderma, Systemic

Intervention / Treatment
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* Drug: Guselkumab Dose 1
* Drug: Guselkumab Dose 2
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: Guselkumab<br>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. | Drug: Guselkumab Dose 1<br>* Guselkumab Dose 1 will be administered intravenously.<br>Drug: Guselkumab Dose 2<br>* Guselkumab Dose 2 will be administered subcutaneously.<br>|
| Placebo Comparator: Group B: Placebo<br>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. | Drug: Placebo<br>* Placebo will be administered intravenously or subcutaneously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 52 | 
| 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. | At Week 24 and Week 52 | 
| 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. | At Week 24 and Week 52 | 
| Change from Baseline in Forced Vital Capacity (FVC) at Week 24 and Week 52 | Pulmonary function test will be assessed by FVC. | Baseline, Week 24, and Week 52 | 
| Change from Baseline in Percent (%) Predicted FVC at Week 24 and Week 52 | Pulmonary function test will be assessed by % predicted FVC. | Baseline, Week 24 and Week 52 | 
| 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. | Baseline, Week 24 and Week 52 | 
| Change from Baseline in the Derived % Predicted DLCO at Week 24 and Week 52 | Pulmonary function test will be assessed by % predicted DLCO. | Baseline, Week 24 and Week 52 | 
| 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. | Baseline, Week 24, and Week 52 | 
| 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. | Baseline, Week 24 and Week 52 | 
| 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. | From baseline up to Week 24, Week 52, Week 76 and Week 104 | 
| 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. | From baseline up to Week 24, Week 52, Week 76 and Week 104 | 
| 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. | From baseline up to Week 24, Week 52, Week 76 and Week 104 | 
| Serum Concentration of Guselkumab | Serum samples will be analyzed to determine concentrations of guselkumab using a validated, specific, and sensitive method. | Up to 112 Weeks (End of study [EOS]/early termination [ET]) | 
| Number of Participants with Antibodies of Guselkumab | Number of participants with incidence antibodies of Guselkumab antibody will be assessed. | Up to 112 Weeks (EOS/ET) |