Clinical trial NCT04138485: Efficacy and Safety of IgPro10 in Adults With Systemic Sclerosis (SSc)
Official title: A Randomized, Multicenter, Double-Blind, Placebo Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of IgPro10 (Intravenous Immunoglobulin, Privigen®) for the Treatment of Adults With Systemic Sclerosis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Diffuse Cutaneous Systemic Sclerosis
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2019-10-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized, multicenter, double-blind (DB), placebo controlled, phase 2 study will evaluate the efficacy and safety of IgPro10. The DB Treatment Period will be followed by a 24-week Open-label (OL) Treatment Period.

Eligible subjects will be randomized at Baseline in a 2:1 ratio of treatment IgPro10 or placebo in the DB Treatment Period. All subjects who enter OL Treatment Period will receive IgPro10.


Eligibility criteria: Inclusion Criteria:

* 1. Age ≥18 years (male or female) at time of providing written informed consent
* Documented diagnosis of SSc according to ACR / EULAR criteria 2013
* mRSS ≥ 15 and ≤ 45
* Disease duration ≤ 5 years defined as the time from the first non-Raynaud's phenomenon manifestation
* Subjects within first 18 months of disease duration from first non-Raynaud's phenomenon manifestation.

Exclusion Criteria:

* Primary rheumatic autoimmune disease other than dcSSc, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, mixed connective tissue disorder, polymyositis, and dermatomyositis, as determined by the investigator Note: Subjects with fibromyalgia, secondary Sjogren's syndrome, and scleroderma-associated myopathy or myositis at Screening are not excluded
* Positive anti-centromere autoantibodies at Screening
* Evidence of severe chronic kidney disease with estimated glomerular filtration rate \< 45 mL/min/1.73 m2 (as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation) or receiving dialysis. Additionally, subjects with current confirmed diagnosis of diabetes mellitus and requiring medication, with eGFR \< 90 mL/min/1.73m2 will be excluded from the study.
* History of documented thrombotic episode eg, PE, DVT, myocardial infarction, thromboembolic stroke at any time Note: past superficial thrombophlebitis more than two years from Screening is not exclusionary
* Documented thrombophilic abnormalities including blood hyperviscosity, protein S or protein C deficiency, anti-thrombin-3 deficiency, plasminogen deficiency, antiphospholipid syndrome, Factor V Leiden mutation, dysfibrinogenemia, or prothrombin G20210A mutation
* Greater than 3 specified current risk factors for TEEs (documented and currents conditions): atrial fibrillation, coronary disease, diabetes mellitus, dyslipidemia, hypertension, obesity (Body Mass Index ≥ 30 kg/m2), recent significant trauma, and immobility (wheelchair-bound or bedridden)
* Ongoing active serious infection at Screening (including, but not limited to, pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, or visceral abscess)
* Malignancy in the past 2 years, except for non-melanoma skin cancer, cervical carcinoma in situ, or other in situ cancer if it has been excised and treated within in the past year
* Known hypoalbuminemia, protein-losing enteropathies, and any proteinuria (defined by total urine protein concentration \> 0.2 g/L)
* Known IgA deficiency or serum IgA level \< 5% lower limit of normal

Primary outcomes:
measure: Response on American College of Rheumatology Combined Response Index in Diffuse Systemic Sclerosis (ACR CRISS) score in IgPro10 vs Placebo
timeFrame: Over 48 weeks
Secondary outcomes:
measure: Proportion of subjects meeting cardiopulmonary or renal failure criteria in ACR CRISS Step 1 events
timeFrame: Over 48 weeks
measure: Proportion of responders (ACR CRISS > 0.6)
timeFrame: Over 48 weeks
measure: Mean change from Baseline in Modified Rodnan Skin Score (mRSS)
timeFrame: Baseline and over48 weeks
measure: Mean change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI)
timeFrame: Baseline and over 48 weeks
measure: Mean change from Baseline in Forced Vital Capacity (FVC)% predicted
timeFrame: Baseline and over 48 weeks
measure: Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted
timeFrame: Baseline and over 48 weeks
measure: Mean change from Baseline in Physician Global Assessment (MDGA)
timeFrame: Baseline and over 48 weeks
measure: Mean change from Baseline in Patient Global Assessment (PGA)
timeFrame: Baseline and over 48 weeks
measure: Mean change from Baseline in UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) total score and subscale
timeFrame: Baseline and over 48 weeks
measure: Mean change from Baseline in Scleroderma Skin Patient Reported Outcome (SSPRO) score in IgPro10 vs Placebo
timeFrame: Baseline and up to 48 weeks
measure: Proportion of responders in mRSS
timeFrame: Up to 48 weeks
measure: Time to treatment failure (time from first infusion to time of first event) in IgPro10 vs Placebo
timeFrame: Over 48 weeks
measure: Proportion of subjects with events at Week 48 in IgPro10 vs Placebo
timeFrame: Over 48 weeks
measure: Mean change from Baseline in Cochin Hand Function Scale in IgPro10 vs Placebo
timeFrame: Baseline and over 48 weeks
measure: Mean change from Baseline in Scleroderma Health Assessment Questionnaire (SHAQ) score in IgPro10 vs Placebo
timeFrame: Baseline and over 48 weeks
measure: Mean change from baseline in muscle strength as measured by Manual Muscle Testing 8 (MMT) in IgPro10 vs Placebo
timeFrame: Baseline and over 48 weeks
measure: Number of subjects with adverse events (AEs) including any AEs, treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs)
timeFrame: Over 48 weeks
measure: Percentage of subjects with AEs, TEAEs, SAEs, AESIs
timeFrame: Over 48 weeks
measure: Concentration of serum trough IgG levels at Baseline and prior to first infusion
timeFrame: Baseline and up to 72 weeks
measure: Mean change from Baseline in Modified Rodnan skin score (mRSS)
timeFrame: Baseline and over 72 weeks
measure: Mean change from Baseline in Patient global assessment (PGA)
timeFrame: Baseline and over 72 weeks
measure: Proportion of responders (ACR CRISS > 0.6)
timeFrame: Over 72 weeks
measure: Mean change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI)
timeFrame: Baseline and over 72 weeks
measure: Mean change from Baseline in Forced Vital Capacity (FVC)% predicted
timeFrame: Baseline and over 72 weeks
measure: Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted
timeFrame: Baseline and over 72 weeks
measure: Mean change from Baseline in Physician Global Assessment (MDGA)
timeFrame: Baseline and over 72 weeks
measure: Number of subjects with adverse events (AEs) including any AEs, treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs)
timeFrame: Over 72 weeks
measure: Percentage of subjects with AEs, TEAEs, SAEs, AESIs
timeFrame: Over 72 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona - Scottsdale
state: Arizona
city: Los Angeles
country: United States
facility: Pacific Arthritis Care Center
state: California
city: Los Angeles
country: United States
facility: University of California
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: Lombardi Cancer Center-Georgetown University
state: District of Columbia
city: Wichita
country: United States
facility: Alliance for Multispecialty Research
state: Kansas
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: John Hopkins Bayview Medical Center
state: Maryland
city: Boston
country: United States
facility: Boston University Amyloidosis Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers Clinical Research Center
state: New Jersey
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Hospital For Special Surgery
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic - Taussig Cancer Center
state: Ohio
city: Duncansville
country: United States
facility: Altoona Center For Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania - Perelman Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: The University Of Texas Medical School At Houston (Utms)
state: Texas
city: Buenos Aires
country: Argentina
facility: APRILLUS Asistencia e Investigacion Clinica
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Militar Central
city: Rosario
country: Argentina
facility: Sanatorio Parque S.A y Consultorios Externos Asociados
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital / Autoimmune Resource and Research Centre
state: New South Wales
city: Adelaide
country: Australia
facility: PARC Clinical Research
state: South Australia
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Toronto
country: Canada
facility: Mount Sinai Hospital, The Rebecca Macdonald Centre For Arthritis
city: Caen
country: France
facility: CHU de Caen
city: Lille Cedex
country: France
facility: CHRU de Lille Hopital Huriez
city: Nantes
country: France
facility: Internal Medicine, Nantes University Hospital
city: Paris
country: France
facility: Assistance Publique - Hopitaux de Paris (AP-HP)
city: Rennes
country: France
facility: CHU de Rennes-Hopital Sud
city: Rouen cedex
country: France
facility: Centre Hospitalier Universitaire de Rouen-Hopital
city: Strasbourg
country: France
facility: CHU Hautepierre
city: Bad Nauheim
country: Germany
facility: Kerckhoff Klinik GmbH, Abteilung für Rheumatologie und Klinische Immunologie Rheumatologie
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Charite Mitte
city: Berlin
country: Germany
facility: Universitaetsmedizin Berlin - Campus Charite Mitte (CCM)
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg- Klinik fuer Rheumatologie und Klinische Immunologie
city: Köln
country: Germany
facility: University Hospital of Cologne
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg
city: Tuebingen
country: Germany
facility: University Hospital Of Tuebingen
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Wuppertal
country: Germany
facility: Hospital St. Josef
city: Ancona
country: Italy
facility: Universita degli Study di Ancona
city: Bari
country: Italy
facility: Universita Degli Studi Di Bari Aldo Moro
city: Brescia
country: Italy
facility: Universita degli Studi Di Brescia
city: Firenze
country: Italy
facility: Universita degli Studi Firenze
city: L'Aquila
country: Italy
facility: UOC Immunoreumatologia
city: Milano
country: Italy
facility: Azienda Ospedaliera Gaetano Pini
city: Modena
country: Italy
facility: Modena University
city: Napoli
country: Italy
facility: Universita degli Studi di Napoli Federico II
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo
city: Rome
country: Italy
facility: Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza
city: Ciudad de México
country: Mexico
facility: Centro de Investigacion y Tratamiento Reumatologico S.C.
city: Guadalajara
country: Mexico
facility: Centro Integral en Reumatologia, SA de CV
city: Jalisco
country: Mexico
facility: Centro De Estudios De Investigation Basica Y Clinica S.C
city: Mexico City
country: Mexico
facility: Cliditer, S.A. DE C.V.
city: Mexico
country: Mexico
facility: Instituto Nacional De Ciencias Medicas Y Nutricion
city: San Luis Potosi
country: Mexico
facility: Centro de Alta Especialidad en Reumatologia
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny W Bialymstoku
city: Gdańsk
country: Poland
facility: University Clinical Centre, Medical University of Gdansk
city: Katowice
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny
city: Warszawa
country: Poland
facility: Klinika Dermatologii Szpital im. Dzieciątka Jezus
city: Warszawa
country: Poland
facility: Klinika i Poliklinika Układowych Chorób Tkanki Łącznej Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji
city: A Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruna
city: Barcelona
country: Spain
facility: Hospital Universitari Materno Infantil Vall Dhebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Univ 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Infanta Luisa Quirónsalud
city: Valencia
country: Spain
facility: Hospital Universitari Dr.Peset
city: Saint Gallen
country: Switzerland
facility: Cantonal Hospital St. Gallen - Klinik fuer Rheumatologie
city: Chester
country: United Kingdom
facility: Countess of Chester Hospital
city: Leeds
country: United Kingdom
facility: Chapel Allerton Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital-Royal Free London NHS Foundation Trust
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: