Efficacy and Safety of IgPro10 in Adults With Systemic Sclerosis (SSc)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Diffuse Cutaneous Systemic Sclerosis
• Intervention / Treatment: Biological: IgPro10; Biological: Placebo

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1194AAO
    • APRILLUS Asistencia e Investigacion Clinica
  • Buenos Aires, Argentina, S2000SDV
    • Hospital Italiano de Buenos Aires
  • Ciudad Autonoma de Buenos Aires, Argentina, C1426AAL
    • Hospital Militar Central
  • Rosario, Argentina, C1181ACH
    • Sanatorio Parque S.A y Consultorios Externos Asociados
• Australia
  • New South Wales
    • New Lambton Heights, New South Wales, Australia, 2305
      • John Hunter Hospital / Autoimmune Resource and Research Centre
  • South Australia
    • Adelaide, South Australia, Australia, 5005
      • PARC Clinical Research
• Belgium
  • Gent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
• Canada
  • Toronto, Canada, M5T 3L9
    • Mount Sinai Hospital, The Rebecca Macdonald Centre For Arthritis
• France
  • Caen, France, 14000
    • CHU de Caen
  • Lille Cedex, France, 59037
    • CHRU de Lille Hopital Huriez
  • Nantes, France, 44000
    • Internal Medicine, Nantes University Hospital
  • Paris, France, 75014
    • Assistance Publique - Hôpitaux de Paris (AP-HP)
  • Rennes, France, 35203
    • CHU de Rennes-Hopital Sud
  • Rouen cedex, France, 76000
    • Centre Hospitalier Universitaire de Rouen-Hopital
  • Strasbourg, France, 67098
    • CHU Hautepierre
• Germany
  • Bad Nauheim, Germany, 61231
    • Kerckhoff Klinik GmbH, Abteilung für Rheumatologie und Klinische Immunologie Rheumatologie
  • Berlin, Germany, 10117
    • Charite - Universitaetsmedizin Berlin - Campus Charite Mitte
  • Berlin, Germany, 10117
    • Universitaetsmedizin Berlin - Campus Charite Mitte (CCM)
  • Freiburg, Germany, 79106
    • Universitaetsklinikum Freiburg- Klinik fuer Rheumatologie und Klinische Immunologie
  • Köln, Germany, 50937
    • University Hospital of Cologne
  • Mainz, Germany, 55131
    • Universitaetsmedizin der Johannes Gutenberg
  • Tuebingen, Germany, 72076
    • University Hospital of Tuebingen
  • Ulm, Germany, 89081
    • Universitaetsklinikum Ulm
  • Wuppertal, Germany, 42105
    • Hospital St. Josef
• Italy
  • Ancona, Italy, 60121
    • Universita degli Study di Ancona
  • Bari, Italy, 70121
    • Università degli studi di Bari Aldo Moro
  • Brescia, Italy, 25123
    • Università degli Studi di Brescia
  • Firenze, Italy, 50139
    • Universita degli Studi Firenze
  • L'Aquila, Italy, 67100
    • UOC Immunoreumatologia
  • Milano, Italy, 20122
    • Azienda Ospedaliera Gaetano Pini
  • Modena, Italy, 41121
    • Modena University
  • Napoli, Italy, 80138
    • Università Degli Studi Di Napoli Federico Ii
  • Pavia, Italy, 27100
    • IRCCS Policlinico San Matteo
  • Rome, Italy, 00161
    • Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza
• Mexico
  • Ciudad de México, Mexico, 11850
    • Centro de Investigación y Tratamiento Reumatológico S.C.
  • Guadalajara, Mexico, 44160
    • Centro Integral en Reumatologia, SA de CV
  • Jalisco, Mexico, 44690
    • Centro De Estudios De Investigation Basica Y Clinica S.C
  • Mexico, Mexico, 14080
    • Instituto Nacional de Ciencias Médicas y Nutrición
  • Mexico City, Mexico, 06700
    • CLIDITER, S.A. de C.V.
  • San Luis Potosi, Mexico, 78213
    • Centro de Alta Especialidad en Reumatologia
• Poland
  • Bialystok, Poland, 15-369
    • Uniwersytecki Szpital Kliniczny w Bialymstoku
  • Gdańsk, Poland, 80-211
    • University Clinical Centre, Medical University of Gdansk
  • Katowice, Poland, 40-635
    • Samodzielny Publiczny Szpital Kliniczny
  • Warszawa, Poland, 00-001
    • Klinika Dermatologii Szpital im. Dzieciątka Jezus
  • Warszawa, Poland, 02-637
    • Klinika i Poliklinika Układowych Chorób Tkanki Łącznej Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji
• Spain
  • A Coruna, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08035
    • Hospital Universitari Materno Infantil Vall Dhebron
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28041
    • Hospital Univ 12 de Octubre
  • Sevilla, Spain, 41010
    • Hospital Infanta Luisa Quirónsalud
  • Valencia, Spain, 46017
    • Hospital Universitari Dr.Peset
• Switzerland
  • Saint Gallen, Switzerland, 9007
    • Cantonal Hospital St. Gallen - Klinik fuer Rheumatologie
• United Kingdom
  • Chester, United Kingdom, CH2 1UL
    • Countess of Chester Hospital
  • Leeds, United Kingdom, LS7 4SA
    • Chapel Allerton Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital-Royal Free London NHS Foundation Trust
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona - Scottsdale
  • California
    • Los Angeles, California, United States, 90095
      • University of California
    • Los Angeles, California, United States, 90045
      • Pacific Arthritis Care Center
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Cancer Center-Georgetown University
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
    • Wichita, Kansas, United States, 67207
      • Alliance for Multispecialty Research
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Louisiana State University Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins Bayview Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Amyloidosis Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48108
      • University of Michigan Health System
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Clinical Research Center
  • New York
    • Great Neck, New York, United States, 11021
      • Northwell Health
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic - Taussig Cancer Center
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Research
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania - Perelman Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • The University Of Texas Medical School At Houston (Utms)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: IgPro10; 10% liquid formulation of human immunoglobulin for intravenous use	Biological: IgPro10; 10% liquid formulation of human immunoglobulin for IVIG; Other Names: Human normal immunoglobulin
PLACEBO_COMPARATOR: Placebo; 0.5% human albumin solution stabilized with 250 mmol/L L-proline	Biological: Placebo; 0.5% human albumin solution stabilized with 250 mmol/L L-proline; Other Names: Albumin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response on American College of Rheumatology Combined Response Index in Diffuse Systemic Sclerosis (ACR CRISS) score in IgPro10 vs Placebo	Over 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects meeting cardiopulmonary or renal failure criteria in ACR CRISS Step 1 events		Over 48 weeks
Proportion of responders (ACR CRISS > 0.6)		Over 48 weeks
Mean change from Baseline in Modified Rodnan Skin Score (mRSS)		Baseline and over48 weeks
Mean change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI)		Baseline and over 48 weeks
Mean change from Baseline in Forced Vital Capacity (FVC)% predicted		Baseline and over 48 weeks
Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted		Baseline and over 48 weeks
Mean change from Baseline in Physician Global Assessment (MDGA)	MDGA evaluates the overall impact of SSc on the participant as assessed by the physician on a 11-point Numeric rating scale scale from 0 (excellent) to 10 (extremely poor)	Baseline and over 48 weeks
Mean change from Baseline in Patient Global Assessment (PGA)	PGA evaluates the overall impact of SSc on the participant as assessed by the physician on a 11-point Numeric rating scale scale from 0 (excellent) to 10 (extremely poor)	Baseline and over 48 weeks
Mean change from Baseline in UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) total score and subscale	This survey consists of 34 questions and items are scored on a scale of 0 (better health) to 3 (worse health). Scores are combined to form total score.	Baseline and over 48 weeks
Mean change from Baseline in Scleroderma Skin Patient Reported Outcome (SSPRO) score in IgPro10 vs Placebo		Baseline and up to 48 weeks
Proportion of responders in mRSS	Response is decrease of mRSS ≥ 5 points and change of ≥ 25% from Baseline in IgPro10 vs Placebo	Up to 48 weeks
Time to treatment failure (time from first infusion to time of first event) in IgPro10 vs Placebo	Treatment failure - defined as occurrence of SSc associated complications in ACR CRISS step 1 events, digital ischemia (requiring hospitalization for IV prostacyclin, surgical intervention or amputation), serious gastrointestinal events (events requiring parenteral nutrition due to SSc -such as total parenteral nutrition or enteral nutrition), all-cause mortality	Over 48 weeks
Proportion of subjects with events at Week 48 in IgPro10 vs Placebo	Events defined as occurrence of SSc associated complications in ACR CRISS step 1 events, digital ischemia (requiring hospitalization for IV prostacyclin, surgical intervention or amputation), serious gastrointestinal events (events requiring parenteral nutrition due to SSc -such as total parenteral nutrition or enteral nutrition), all -cause mortality	Over 48 weeks
Mean change from Baseline in Cochin Hand Function Scale in IgPro10 vs Placebo		Baseline and over 48 weeks
Mean change from Baseline in Scleroderma Health Assessment Questionnaire (SHAQ) score in IgPro10 vs Placebo		Baseline and over 48 weeks
Mean change from baseline in muscle strength as measured by Manual Muscle Testing 8 (MMT) in IgPro10 vs Placebo		Baseline and over 48 weeks
Number of subjects with adverse events (AEs) including any AEs, treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs)		Over 48 weeks
Percentage of subjects with AEs, TEAEs, SAEs, AESIs		Over 48 weeks
Concentration of serum trough IgG levels at Baseline and prior to first infusion		Baseline and up to 72 weeks
Mean change from Baseline in Modified Rodnan skin score (mRSS)		Baseline and over 72 weeks
Mean change from Baseline in Patient global assessment (PGA)		Baseline and over 72 weeks
Proportion of responders (ACR CRISS > 0.6)		Over 72 weeks
Mean change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI)		Baseline and over 72 weeks
Mean change from Baseline in Forced Vital Capacity (FVC)% predicted		Baseline and over 72 weeks
Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted		Baseline and over 72 weeks
Mean change from Baseline in Physician Global Assessment (MDGA)		Baseline and over 72 weeks
Number of subjects with adverse events (AEs) including any AEs, treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs)		Over 72 weeks
Percentage of subjects with AEs, TEAEs, SAEs, AESIs		Over 72 weeks

Collaborators and Investigators

• Sponsor: CSL Behring

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 20, 2019
• Primary Completion (ACTUAL): September 16, 2020
• Study Completion (ACTUAL): September 16, 2020

Study Registration Dates

• First Submitted: October 14, 2019
• First Submitted That Met QC Criteria: October 22, 2019
• First Posted (ACTUAL): October 24, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 17, 2020
• Last Update Submitted That Met QC Criteria: November 16, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins
• Other Study ID Numbers: IgPro10_2001; 2019-000906-31 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

CSL will consider requests to share Individual Patient Data (IPD) from systemic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Time Frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.

IPD Sharing Access Criteria

Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.

An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.

The requesting party must execute an appropriate data sharing agreement before IPD will be made available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No