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

Sponsor
CSL Behring (Industry)
Overall Status
Withdrawn
CT.gov ID
NCT04138485
Collaborator
(none)
0
Enrollment
77
Locations
2
Arms
8.9
Actual Duration (Months)
0
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: IgPro10
  • Biological: Placebo
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 20, 2019
Actual Primary Completion Date :
Sep 16, 2020
Actual Study Completion Date :
Sep 16, 2020

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. Proportion of subjects meeting cardiopulmonary or renal failure criteria in ACR CRISS Step 1 events [Over 48 weeks]

    2. Proportion of responders (ACR CRISS > 0.6) [Over 48 weeks]

    3. Mean change from Baseline in Modified Rodnan Skin Score (mRSS) [Baseline and over48 weeks]

    4. Mean change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) [Baseline and over 48 weeks]

    5. Mean change from Baseline in Forced Vital Capacity (FVC)% predicted [Baseline and over 48 weeks]

    6. Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted [Baseline and over 48 weeks]

    7. Mean change from Baseline in Physician Global Assessment (MDGA) [Baseline and over 48 weeks]

      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)

    8. Mean change from Baseline in Patient Global Assessment (PGA) [Baseline and over 48 weeks]

      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)

    9. Mean change from Baseline in UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) total score and subscale [Baseline and over 48 weeks]

      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.

    10. Mean change from Baseline in Scleroderma Skin Patient Reported Outcome (SSPRO) score in IgPro10 vs Placebo [Baseline and up to 48 weeks]

    11. Proportion of responders in mRSS [Up to 48 weeks]

      Response is decrease of mRSS ≥ 5 points and change of ≥ 25% from Baseline in IgPro10 vs Placebo

    12. Time to treatment failure (time from first infusion to time of first event) in IgPro10 vs Placebo [Over 48 weeks]

      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

    13. Proportion of subjects with events at Week 48 in IgPro10 vs Placebo [Over 48 weeks]

      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

    14. Mean change from Baseline in Cochin Hand Function Scale in IgPro10 vs Placebo [Baseline and over 48 weeks]

    15. Mean change from Baseline in Scleroderma Health Assessment Questionnaire (SHAQ) score in IgPro10 vs Placebo [Baseline and over 48 weeks]

    16. Mean change from baseline in muscle strength as measured by Manual Muscle Testing 8 (MMT) in IgPro10 vs Placebo [Baseline and over 48 weeks]

    17. 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]

    18. Percentage of subjects with AEs, TEAEs, SAEs, AESIs [Over 48 weeks]

    19. Concentration of serum trough IgG levels at Baseline and prior to first infusion [Baseline and up to 72 weeks]

    20. Mean change from Baseline in Modified Rodnan skin score (mRSS) [Baseline and over 72 weeks]

    21. Mean change from Baseline in Patient global assessment (PGA) [Baseline and over 72 weeks]

    22. Proportion of responders (ACR CRISS > 0.6) [Over 72 weeks]

    23. Mean change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) [Baseline and over 72 weeks]

    24. Mean change from Baseline in Forced Vital Capacity (FVC)% predicted [Baseline and over 72 weeks]

    25. Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted [Baseline and over 72 weeks]

    26. Mean change from Baseline in Physician Global Assessment (MDGA) [Baseline and over 72 weeks]

    27. 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]

    28. Percentage of subjects with AEs, TEAEs, SAEs, AESIs [Over 72 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • CSL Behring

    Investigators

    • Study Director: Study Director, CSL Behring

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    CSL Behring
    ClinicalTrials.gov Identifier:
    NCT04138485
    Other Study ID Numbers:
    • IgPro10_2001
    • 2019-000906-31
    First Posted:
    Oct 24, 2019
    Last Update Posted:
    Nov 17, 2020
    Last Verified:
    Nov 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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
    Additional relevant MeSH terms:
    Scleroderma, Systemic
    Scleroderma, Diffuse
    Sclerosis
    Immunoglobulins

    Study Results

    No Results Posted as of Nov 17, 2020