A study of Guselkumab in Participants with Systemic Sclerosis

JRCT ID: jRCT2051200133

Registered date:12/02/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Scleroderma, Systemic
• Date of first enrollment: 31/03/2021
• Target sample size: 56
• Study type: Interventional

Intervention(s)

Group A: Guselkumab Dose 1
Guselkumab Dose 1 will be administered intravenously.

Group A: Guselkumab Dose 2
Guselkumab Dose 2 will be administered subcutaneously.

Group B: Placebo
Placebo will be administered intravenously or subcutaneously.

Outcome(s)

Primary Outcome

Change from Baseline in Modified Rodnan Skin Score (mRSS) at Week 24
Baseline and 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

Change From Baseline in mRSS at Week 52

Percentage of Participants with Worsening of mRSS 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.

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 Forced Vital Capacity (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)
From baseline up to Week 24, Week 52, Week 76 and Week 104
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)
From baseline up to Week 24, Week 52, Week 76 and Week 104
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)
From baseline up to Week 24, Week 52, Week 76 and Week 104
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.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 75age old
• Gender: Both

Include 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

Exclude 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)

Related Information

• Primary Sponsor: Numaguchi Hirotaka
• Secondary ID(s): NCT04683029