A Study of Guselkumab in Participants With Systemic Sclerosis

Scleroderma, Systemic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04683029
• Other study ID #: CR108936
• Secondary ID: CNTO1959SSC2001
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 24, 2021
• Est. completion date: July 5, 2024

Study information

• Verified date: April 2024
• Source: Janssen Pharmaceutical K.K.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 56
• Est. completion date: July 5, 2024
• Est. primary completion date: May 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic

Intervention

Drug:
• Guselkumab Dose 1
Guselkumab Dose 1 will be administered intravenously.
• Guselkumab Dose 2
Guselkumab Dose 2 will be administered subcutaneously.
• Placebo
Placebo will be administered intravenously or subcutaneously.

Locations

Country	Name	City	State
Japan	Chukyo Hospital	Aichi
Japan	The University of Tokyo Hospital	Tokyo
Japan	Wakayama Medical University Hospital	Wakayama
Japan	University of Fukui Hospital	Yoshida

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Pharmaceutical K.K.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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])
Secondary	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)