A Study of Guselkumab in Participants With Systemic Sclerosis

Phase 2

Completed

Conditions: Scleroderma, Systemic

Interventions: Drug: Guselkumab Dose 1
Drug: Placebo
Drug: Guselkumab Dose 2

Registration Number: NCT04683029

Lead Sponsor: Janssen Pharmaceutical K.K.

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 56

Inclusion Criteria

Not provided

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A: Guselkumab	Guselkumab Dose 2	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.
Group A: Guselkumab	Guselkumab Dose 1	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.
Group B: Placebo	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24	Baseline and Week 24	Change from baseline in mRSS at Week 24 was reported. The mRSS is an accepted clinical measure of skin thickness. The investigator assessed the thickening of the skin using the mRSS through simple palpation on 17 different skin sites in the fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). Each skin site was rated on a 0 to 3 scale; where 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness and unable to pinch. Individual skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (no thickening) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Modified Rodnan Skin Score at Week 52	Baseline and Week 52	Change from baseline in mRSS at Week 52 was reported. The mRSS is an accepted clinical measure of skin thickness. The investigator assessed the thickening of the skin using the mRSS through simple palpation on 17 different skin sites in the fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). Each skin site was rated on a 0 to 3 scale; where 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness and unable to pinch. Individual skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (no thickening) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome.
Percentage of Participants Who Experienced Worsening of Modified Rodnan Skin Score at Week 24 and Week 52	Week 24 and Week 52	The percentage of participants who experienced worsening of mRSS at Week 24 and Week 52 was reported. The worsening of mRSS was defined as an increase from baseline greater than or equal to (\>=) 5 points and \>=20 percent (%) in mRSS. The mRSS is an accepted clinical measure of skin thickness. The investigator assessed the thickening of the skin using the mRSS through simple palpation on 17 different skin sites in the fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). Each skin site was rated on a 0 to 3 scale; where 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness and unable to pinch. Individual skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (no thickening) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome.
Percentage of Participants Who Achieved a Score of 0.6 in American College of Rheumatology Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (ACR CRISS) at Week 24 and Week 52	Week 24 and Week 52	ACR CRISS is a composite endpoint. Firstly, participants were evaluated on not-improved criterion: new onset of renal crisis, \>=15% decline in forced vital capacity \[FVC\] percent predicted relative to baseline, new onset of pulmonary arterial hypertension, and new onset of left ventricular failure. If yes, these participants were assigned probability score of 0.0. For remaining participants, percentage was based on CRISS domains: mRSS, FVC percent predicted, physician's global assessment, patient's global assessment and Health Assessment Questionnaire Disability-Index (HAQ-DI). Algorithm determines predicted probability of improvement from baseline by incorporating change in mRSS, FVC percent predicted, physician and patient global assessments and HAQ-DI. Outcome was a continuous variable between 0.0 and 1.0 (0 to 100%). Higher score=greater probability of improvement. ACR CRISS score \>=0.60 was considered improved, while predicted probability below 0.60 was considered not improved.
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 24 and Week 52	Baseline, Week 24 and Week 52	Change from baseline in the percent predicted FVC at Week 24 and Week 52 was reported. FVC was the total amount of air (in liters) exhaled from the lungs during the lung function test measured by spirometer which assessed the change in lung function related to the disease status of an underlying interstitial lung disease.
Change From Baseline in the Measured Absolute Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) at Week 24 and Week 52	Baseline, Week 24 and Week 52	DLCO is a measurement of the ability of the lungs to transfer gases from the air to the blood. DLCO is measured using the single breath method. Participants breathe in (inhale) air containing a very small, harmless amount of a tracer gas, such as carbon monoxide. Participants hold their breath for 10 seconds, then rapidly blow it out (exhale). The exhaled gas was tested to determine amount of the tracer gas absorbed during the breath.
Change From Baseline in the Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) at Week 24 and Week 52	Baseline, Week 24 and Week 52	Change from baseline in the percent predicted DLCO at Week 24 and Week 52 was reported. DLCO is a measurement of the ability of the lungs to transfer gases from the air to the blood. DLCO is measured using the single breath method. Participants breathe in (inhale) air containing a very small, harmless amount of a tracer gas, such as carbon monoxide. Participants hold their breath for 10 seconds, then rapidly blow it out (exhale). The exhaled gas was tested to determine amount of the tracer gas absorbed during the breath.
Change From Baseline in Digital Ulcer Counts at Week 24 and Week 52	Baseline, Week 24 and Week 52	Digital ulcers were defined as a full thickness (\>3 millimeters \[mm\] in maximal diameter) skin lesion with loss of epithelium including lesions covered by eschar (excluding pitting scars and hyperkeratotic lesions). Healing was defined by re-epithelialization with loss of pain and exudate. The digital ulcer assessments and counting were performed by the investigator designee.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 and Week 52	Baseline, Week 24 and Week 52	HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during past week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each activity category consisted of 2-3 items. For each item, level of difficulty was scored from 0 to 3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Total HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0 (no difficulty) to 3 (maximum difficulty), where higher score indicated greater disability.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Through Week 24 and Week 52	From Baseline (Week 0) up to Week 24 and Week 52	An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs were defined as AEs that occur at or after the initial administration of study intervention. All TEAEs including serious and non-serious events are reported in this outcome measure.
Change From Baseline in Forced Vital Capacity (FVC) at Week 24 and Week 52	Baseline, Week 24 and Week 52	FVC was the total amount of air (in liters) exhaled from the lungs during the lung function test measured by spirometer which assessed the change in lung function related to the disease status of an underlying interstitial lung disease.
Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) Through Week 24 and Week 52	From Baseline (Week 0) up to Week 24 and Week 52	An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or resulted in congenital anomaly/birth defect. TEAEs were defined as AEs that occur at or after the initial administration of study intervention.
Number of Participants With Adverse Events of Special Interest (AESI) Through Week 24 and Week 52	From Baseline (Week 0) up to Week 24 and Week 52	AESI were defined as any newly identified malignancy or case of active tuberculosis (TB) or interstitial lung disease (ILD) occurring after the first study intervention administration in study participants and was reported by the investigator to the sponsor or designee within 24 hours after being made aware of the event. AESIs for this study included drug-induced liver injuries, active TB, ILD, hypersensitivity reaction, opportunistic infection and adverse cardiovascular events.
Serum Concentration of Guselkumab	Pre-dose at Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Post- dose at Weeks 0, 4, 8	Serum concentration of guselkumab was reported. The lower limit of quantification (LLOQ) for guselkumab was 0.01 micrograms per milliliter (mcg/mL).
Number of Participants With Anti-Guselkumab Antibody	From Baseline (Week 0) up to Week 52	Number of participants with anti-guselkumab antibody were reported. Serum samples were assessed for anti-drug antibodies.

Trial Locations

Locations (4): Chukyo Hospital
🇯🇵
Aichi, Japan
The University of Tokyo Hospital
🇯🇵
Tokyo, Japan
Wakayama Medical University Hospital
🇯🇵
Wakayama, Japan
University of Fukui Hospital
🇯🇵
Yoshida, Japan
Chukyo Hospital
🇯🇵Aichi, Japan