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

Diffuse Cutaneous Systemic Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04138485
• Other study ID #: IgPro10_2001
• Secondary ID: 2019-000906-31
• Status: Withdrawn
• Phase: Phase 2
• Start date: December 20, 2019
• Est. completion date: September 16, 2020

Study information

• Verified date: November 2020
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 16, 2020
• Est. primary completion date: September 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Cutaneous Systemic Sclerosis
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis

Intervention

Biological:
• IgPro10
10% liquid formulation of human immunoglobulin for IVIG
• Placebo
0.5% human albumin solution stabilized with 250 mmol/L L-proline

Locations

Country	Name	City	State
Argentina	APRILLUS Asistencia e Investigacion Clinica	Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	Hospital Militar Central	Ciudad Autonoma de Buenos Aires
Argentina	Sanatorio Parque S.A y Consultorios Externos Asociados	Rosario
Australia	PARC Clinical Research	Adelaide	South Australia
Australia	John Hunter Hospital / Autoimmune Resource and Research Centre	New Lambton Heights	New South Wales
Belgium	UZ Gent	Gent
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Canada	Mount Sinai Hospital, The Rebecca Macdonald Centre For Arthritis	Toronto
France	CHU de Caen	Caen
France	CHRU de Lille Hopital Huriez	Lille Cedex
France	Internal Medicine, Nantes University Hospital	Nantes
France	Assistance Publique - Hopitaux de Paris (AP-HP)	Paris
France	CHU de Rennes-Hopital Sud	Rennes
France	Centre Hospitalier Universitaire de Rouen-Hopital	Rouen cedex
France	CHU Hautepierre	Strasbourg
Germany	Kerckhoff Klinik GmbH, Abteilung für Rheumatologie und Klinische Immunologie Rheumatologie	Bad Nauheim
Germany	Charite - Universitaetsmedizin Berlin - Campus Charite Mitte	Berlin
Germany	Universitaetsmedizin Berlin - Campus Charite Mitte (CCM)	Berlin
Germany	Universitaetsklinikum Freiburg- Klinik fuer Rheumatologie und Klinische Immunologie	Freiburg
Germany	University Hospital of Cologne	Köln
Germany	Universitaetsmedizin der Johannes Gutenberg	Mainz
Germany	University Hospital Of Tuebingen	Tuebingen
Germany	Universitaetsklinikum Ulm	Ulm
Germany	Hospital St. Josef	Wuppertal
Italy	Universita degli Study di Ancona	Ancona
Italy	Universita Degli Studi Di Bari Aldo Moro	Bari
Italy	Universita degli Studi Di Brescia	Brescia
Italy	Universita degli Studi Firenze	Firenze
Italy	UOC Immunoreumatologia	L'Aquila
Italy	Azienda Ospedaliera Gaetano Pini	Milano
Italy	Modena University	Modena
Italy	Universita degli Studi di Napoli Federico II	Napoli
Italy	IRCCS Policlinico San Matteo	Pavia
Italy	Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza	Rome
Mexico	Centro de Investigacion y Tratamiento Reumatologico S.C.	Ciudad de México
Mexico	Centro Integral en Reumatologia, SA de CV	Guadalajara
Mexico	Centro De Estudios De Investigation Basica Y Clinica S.C	Jalisco
Mexico	Instituto Nacional De Ciencias Medicas Y Nutricion	Mexico
Mexico	Cliditer, S.A. DE C.V.	Mexico City
Mexico	Centro de Alta Especialidad en Reumatologia	San Luis Potosi
Poland	Uniwersytecki Szpital Kliniczny W Bialymstoku	Bialystok
Poland	University Clinical Centre, Medical University of Gdansk	Gdansk
Poland	Samodzielny Publiczny Szpital Kliniczny	Katowice
Poland	Klinika Dermatologii Szpital im. Dzieciatka Jezus	Warszawa
Poland	Klinika i Poliklinika Ukladowych Chorób Tkanki Lacznej Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji	Warszawa
Spain	Complejo Hospitalario Universitario A Coruna	A Coruna
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Materno Infantil Vall Dhebron	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Univ 12 de Octubre	Madrid
Spain	Hospital Infanta Luisa Quirónsalud	Sevilla
Spain	Hospital Universitari Dr.Peset	Valencia
Switzerland	Cantonal Hospital St. Gallen - Klinik fuer Rheumatologie	Saint Gallen
United Kingdom	Countess of Chester Hospital	Chester
United Kingdom	Chapel Allerton Hospital	Leeds
United Kingdom	Royal Free Hospital-Royal Free London NHS Foundation Trust	London
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	John Hopkins Bayview Medical Center	Baltimore	Maryland
United States	Boston University Amyloidosis Center	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Cleveland Clinic - Taussig Cancer Center	Cleveland	Ohio
United States	Altoona Center For Research	Duncansville	Pennsylvania
United States	Northwell Health	Great Neck	New York
United States	The University Of Texas Medical School At Houston (Utms)	Houston	Texas
United States	Pacific Arthritis Care Center	Los Angeles	California
United States	University of California	Los Angeles	California
United States	Rutgers Clinical Research Center	New Brunswick	New Jersey
United States	Hospital For Special Surgery	New York	New York
United States	Stanford University Medical Center	Palo Alto	California
United States	University of Pennsylvania - Perelman Center	Philadelphia	Pennsylvania
United States	Mayo Clinic Arizona - Scottsdale	Scottsdale	Arizona
United States	Louisiana State University Health Sciences Center	Shreveport	Louisiana
United States	Lombardi Cancer Center-Georgetown University	Washington	District of Columbia
United States	Alliance for Multispecialty Research	Wichita	Kansas
United States	Heartland Research Associates, LLC	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  France,  Germany,  Italy,  Mexico,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response on American College of Rheumatology Combined Response Index in Diffuse Systemic Sclerosis (ACR CRISS) score in IgPro10 vs Placebo		Over 48 weeks
Secondary	Proportion of subjects meeting cardiopulmonary or renal failure criteria in ACR CRISS Step 1 events		Over 48 weeks
Secondary	Proportion of responders (ACR CRISS > 0.6)		Over 48 weeks
Secondary	Mean change from Baseline in Modified Rodnan Skin Score (mRSS)		Baseline and over48 weeks
Secondary	Mean change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI)		Baseline and over 48 weeks
Secondary	Mean change from Baseline in Forced Vital Capacity (FVC)% predicted		Baseline and over 48 weeks
Secondary	Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted		Baseline and over 48 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	Mean change from Baseline in Scleroderma Skin Patient Reported Outcome (SSPRO) score in IgPro10 vs Placebo		Baseline and up to 48 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	Mean change from Baseline in Cochin Hand Function Scale in IgPro10 vs Placebo		Baseline and over 48 weeks
Secondary	Mean change from Baseline in Scleroderma Health Assessment Questionnaire (SHAQ) score in IgPro10 vs Placebo		Baseline and over 48 weeks
Secondary	Mean change from baseline in muscle strength as measured by Manual Muscle Testing 8 (MMT) in IgPro10 vs Placebo		Baseline and over 48 weeks
Secondary	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
Secondary	Percentage of subjects with AEs, TEAEs, SAEs, AESIs		Over 48 weeks
Secondary	Concentration of serum trough IgG levels at Baseline and prior to first infusion		Baseline and up to 72 weeks
Secondary	Mean change from Baseline in Modified Rodnan skin score (mRSS)		Baseline and over 72 weeks
Secondary	Mean change from Baseline in Patient global assessment (PGA)		Baseline and over 72 weeks
Secondary	Proportion of responders (ACR CRISS > 0.6)		Over 72 weeks
Secondary	Mean change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI)		Baseline and over 72 weeks
Secondary	Mean change from Baseline in Forced Vital Capacity (FVC)% predicted		Baseline and over 72 weeks
Secondary	Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted		Baseline and over 72 weeks
Secondary	Mean change from Baseline in Physician Global Assessment (MDGA)		Baseline and over 72 weeks
Secondary	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
Secondary	Percentage of subjects with AEs, TEAEs, SAEs, AESIs		Over 72 weeks