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Study of the Efficacy and Safety of Immune Globulin Intravenous (Human) Flebogamma® 5% DIF in Patients With Post-polio Syndrome (FORCE)

This study is currently recruiting participants.
Verified August 2017 by Grifols Biologicals Inc. ( Instituto Grifols, S.A. )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02176863
First Posted: June 27, 2014
Last Update Posted: August 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Grifols Biologicals Inc. ( Instituto Grifols, S.A. )
  Purpose

This is a multicenter, prospective, randomized, placebo-controlled, double-blind, parallel group clinical trial with adaptive dose selection in subjects with post polio syndrome (PPS).

The main purpose of this study is to select a dose of Flebogamma 5% DIF and confirm the efficacy of the selected Flebogamma 5% DIF dose by assessing physical performance, as measured by 2 Minutes Walk Distance (2MWD) test.


Condition Intervention Phase
Post-polio Syndrome Biological: Flebogamma 5% DIF Other: Placebo Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Prospective, Randomized, Placebo-controlled, Double-blind, Parallel‑Group Clinical Trial to Assess the Efficacy and Safety of Immune Globulin Intravenous (Human) Flebogamma® 5% DIF in Patients With Post-Polio Syndrome

Resource links provided by NLM:


Further study details as provided by Grifols Biologicals Inc. ( Instituto Grifols, S.A. ):

Primary Outcome Measures:
  • Change from baseline in 2MWD [ Time Frame: Baseline, Week 52 ]
    Physical performance (2MWD) from baseline (at Enrollment Visit) to the end of the treatment period


Secondary Outcome Measures:
  • Change from baseline in Visual Analogue Scale (VAS) of pain [ Time Frame: Baseline, Week 52 ]
    Pain (Visual Analogue Scale [VAS] of pain) from baseline to the end of the treatment period.

  • Change from baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) [ Time Frame: Baseline, Week 52 ]
    HRQoL (Medical Outcomes Study 36-Item Short Form Health Survey [SF-36] Physical Component Summary

  • Change from baseline in Six Minutes Walk Distance (6MWD) [ Time Frame: Baseline, Week 52 ]
    Endurance (Six-Minute Walk Distance [6MWD]) from baseline to the end of the treatment period.


Other Outcome Measures:
  • Muscle Strength of two newly weakened muscle groups (MMT using the MRC scale) [ Time Frame: Baseline, Week 52 ]
    Muscle strength of 2 newly weakened muscle groups (Manual Muscle Testing [MMT] using the Medical Research Council [MRC] scale) from baseline to the end of the treatment period.

  • Muscle strength of two newly weakened muscle groups (QMT using a dynamometer) [ Time Frame: Baseline, Week 52 ]
    Muscle strength of 2 newly weakened muscle groups (Quantitative Muscle Testing [QMT] using a dynamometer) from baseline to the end of the treatment period.

  • Walking activity in daily life (pedometer) [ Time Frame: Baseline, Week 52 ]
    Walking activity in daily life (pedometer)

  • Subject's self-perceived exertion/fatigue level using the Borg scale [ Time Frame: Baseline, Week 52 ]
    Subject's self-perceived exertion/fatigue level using the Borg scale

  • Fatigue (FSS) [ Time Frame: Baseline, Week 52 ]
    Fatigue (FSS)

  • HRQoL (SF-36 MCS) [ Time Frame: Baseline, Week 52 ]
    HRQoL (SF-36 MCS)

  • Blood and CSF (CSF is optional) inflammatory cytokines [ Time Frame: Baseline, Week 52 ]
    Blood and CSF (CSF is optional) inflammatory cytokines

  • Sustained effect of Flebogamma 5% DIF compared to placebo [ Time Frame: Baseline, Week 76 ]

    Sustained effect of Flebogamma® 5% DIF compared to placebo as measured by:

    • Physical performance (2MWD) from baseline to FU3 (Week 64) and to the FV (Week 76).
    • Pain (VAS of pain) from baseline to FU3 and to the FV.
    • HRQoL (SF-36 PCS) from baseline to FU3 and to the FV.
    • Endurance (6MWD) from baseline to FU3 and to the FV
    • Muscle strength (MMT using the MRC scale) from baseline to the FV.
    • Muscle strength (QMT using a dynamometer) from baseline to the FV.
    • Walking activity in daily life (pedometer) from baseline to the FV.
    • Fatigue (FSS) from baseline to the FV.
    • HRQoL (SF-36 MCS) from baseline to FU3 and to the FV.
    • Blood and CSF (CSF is optional) inflammatory cytokines from baseline to the FV.


Estimated Enrollment: 210
Study Start Date: July 2014
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 2 g/kg Flebogamma 5% DIF
Flebogamma 5% DIF, 2 g/kg, intravenous infusion every 4 weeks over two days for 52 weeks
Biological: Flebogamma 5% DIF
Human plasma-derived immunoglobulin
Other Name: immune globulin intravenous (human)
Experimental: 1 g/kg Flebogamma 5% DIF
Flebogamma 5% DIF, 1 g/kg, intravenous infusion every 4 weeks over two days for 52 weeks
Biological: Flebogamma 5% DIF
Human plasma-derived immunoglobulin
Other Name: immune globulin intravenous (human)
Placebo Comparator: Placebo
Normal Saline Solution, matching volume, intravenous infusion every 4 weeks over two days for 52 weeks
Other: Placebo
Normal saline solution

  Hide Detailed Description

Detailed Description:

This is a phase II/III multicentre, prospective, randomized, placebo-controlled, double-blind, parallel‑group clinical trial with an adaptive design (flexible group sequential design with adaptive dose selection) in subjects with PPS.

This study will consist of two stages. The first stage (Stage 1) is for dose selection, and the second stage (Stage 2) is to establish the superiority (efficacy confirmation) of Flebogamma® 5% DIF and for overall safety analysis. At Stage 1, three treatment arms, Flebogamma® 5% DIF 2 g/kg of body weight (IVIG 2 g/kg arm), or the equivalent volume of Normal Saline Solution (40 ml/kg of body weight), or Flebogamma® 5% DIF 1 g/kg of body weight plus the equivalent volume of Normal Saline Solution (20 ml/kg of body weight) (IVIG 1 g/kg arm) will be administered every 4 weeks over two consecutive days during a 52-week treatment period. At Stage 2, two treatment arms, the selected dose of Flebogamma® 5% DIF from Stage 1 and Normal Saline Solution (40 ml/kg of body weight), will be administered every 4 weeks over two consecutive days during a 52-week treatment period. During Stage 2, the selected dose of Flebogamma® 5% DIF and Normal Saline Solution will be administered in the same manner as in Stage 1, including administering the total dose for both treatment arms at a volume equivalent to that for the IVIG 2 g/kg arm, regardless of the selected dose.

Primary efficacy endpoint will be:

  • Physical performance (2MWD) from baseline to the end of the treatment period (at End of Treatment Visit -Week 52).

Secondary efficacy endpoints will be:

  • Pain (VAS of pain) from baseline to the end of the treatment period.
  • HRQoL (SF-36 PCS) from baseline to the end of the treatment period.
  • Endurance (6MWD) from baseline to the end of the treatment period.

Exploratory endpoints will be:

  • Muscle strength of at least two newly weakened muscle groups (Manual Muscle Testing [MMT] using the modified Medical Research Council [MRC] scale) from baseline to the end of the treatment period.
  • Muscle strength of at least two newly weakened muscle groups (Quantitative Muscle Testing [QMT] using a dynamometer) from baseline to the end of the treatment period.
  • Walking activity in daily life (pedometer) from baseline to the end of the treatment period.
  • Subject's self-perceived exertion/fatigue level using the Borg scale before and after the 2MWD and 6MWD from baseline to the end of the treatment period.
  • Fatigue (Fatigue Severity Scale [FSS]) from baseline to the end of the treatment period.
  • HRQoL (SF-36 Mental Component Summary [MCS]) from baseline to the end of the treatment period.
  • Blood and CSF (CSF is optional) inflammatory cytokines (IL-1, IL-4, IL-6, IL-10, IL-13, IL-17, IL-23, TNF-alpha, and IFN-gamma) from baseline to the end of the treatment period.
  • Sustained effect of Flebogamma® 5% DIF compared to placebo as measured by:

    1. Physical performance (2MWD) from baseline to Followup Visit (FU) (Week 64) and to the Final Visit (FV; Week 76).
    2. Pain (VAS of pain) from baseline to FU3 and to the FV.
    3. HRQoL (SF-36 PCS) from baseline to FU3 and to the FV.
    4. Endurance (6MWD) from baseline to FU3 and to the FV.
    5. Muscle strength (MMT using the MRC scale) from baseline to the FV.
    6. Muscle strength (QMT using a dynamometer) from baseline to the FV.
    7. Walking activity in daily life (pedometer) from baseline to the FV.
    8. Fatigue (FSS) from baseline to the FV.
    9. HRQoL (SF-36 MCS) from baseline to FU3 and to the FV.
    10. Blood and CSF (CSF is optional) inflammatory cytokines from baseline to the FV.

Safety endpoints will include Adverse Events (AEs), vital signs during infusions, physical assessments and blood tests for clinical safety.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • BMI less than 35 kg/m2.
  • March-of-Dimes clinical criteria for diagnosis of PPS.
  • Ambulatory or are able to walk with a cane or other aids or use a wheelchair (but they are not wheelchair-bound).
  • Subjects who have at least 2 newly weakened muscle groups due to PPS (as defined by medical history), with at least 1 of them in a lower extremity, and having an MRC scale score greater than 3 at the MMT performed by the independent assessor at the SV.
  • Female of child-bearing potential must have a negative test for pregnancy.
  • Female of child-bearing potential and their sexual partners have agreed to practice contraception using a method of proven reliability.
  • Able to walk a 2MWD of at least 50 meters.
  • Subjects who are able to walk a consistent baseline 2 MWD, that is, the difference in 2MWD between the SV and EV/IV1 is not more than 10%.

Exclusion Criteria:

  • Have received human normal immune globulin treatment given by intravenous, subcutaneous or intramuscular route within the last 3 years.
  • Are not ambulatory (wheelchair-bound individuals).
  • Poor venous access.
  • Intractable pain requiring narcotics or other psychotropic drugs.
  • History of anaphylactic reactions or severe reactions to any blood-derived product.
  • History of intolerance to any component of the investigational products, such as sorbitol.
  • Receiving corticosteroids, except for those for asthma.
  • Documented diagnosis of hyperviscosity or hypercoagulable state or thrombotic complications to polyclonal IVIG therapy in the past.
  • History of recent (within the last year) myocardial infarction, stroke, or uncontrolled hypertension.
  • Suffer from congestive heart failure, embolism, or electrocardiogram changes indicative of unstable angina or atrial fibrillation.
  • History of chronic alcoholism or illicit drug abuse (addiction) in the preceding 12 months.
  • Active psychiatric illness that interferes with compliance or communication with health care personnel.
  • Depression with scores >30 as assessed by the Center for Epidemiologic Studies Depression validated scale.
  • Females who are pregnant or are nursing an infant child.
  • Currently receiving, or have received within 3 months prior to the Screening Visit, any investigational medicinal product or device.
  • Known selective IgA deficiency and serum antibodies anti-IgA.
  • Renal impairment (i.e., serum creatinine exceeds more than 1.5 time the upper limit of normal (ULN).
  • Subjects with aspartate aminotransferase or alanine aminotransferase levels exceeding more than 2.5 times the ULN.
  • Hemoglobin levels <10 mg/dL, platelets levels <100,000/mm3, white blood cells count <3.0 k/µL and ESR >50 mm/h or twice above normal.
  • Known seropositive to Hepatitis C virus, Human immunodeficiency virus-1 and/or -2.
  • Subjects with a history of intolerance to fructose.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02176863


Contacts
Contact: Sandra Camprubi sandra.camprubi@grifols.com
Contact: Karen Rucker karen.rucker@grifols.com

Locations
United States, California
University of California Recruiting
Los Angeles, California, United States, 90095
Contact: Aaron Fisher    310-206-8153    ADFisher@mednet.ucla.edu   
Principal Investigator: Susan Perlman, MD         
United States, Missouri
Washington University Completed
Saint Louis, Missouri, United States, 63110
United States, New York
SUNY Upstate Medical University Recruiting
Syracuse, New York, United States, 13210
Contact: Courtney Goodrich    315-464-6409    goodricc@upstate.edu   
Principal Investigator: Burke Jubelt, MD         
United States, Pennsylvania
Thomas Jefferson University Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Lauren E Fedor    215-955-4663    Lauren.Fedor@jefferson.edu   
Principal Investigator: Marinos Dalakas         
Canada, Quebec
Montreal Neurological Institute, McGill University Recruiting
Montreal, Quebec, Canada, H3A 2B4
Contact: Claire Magnussen, PhD    5143983729    claire.magnussen@mcgill.ca   
Principal Investigator: Daria Trojan, MD         
Denmark
Aarhus Universitets Hospital Recruiting
Aarhus C, Denmark, 8000
Contact: Anita Mogensen       aniole@rm.dk   
Contact: Anne Sofie Kjaer       as.kjaer@outlook.com   
Principal Investigator: Henning Andersen, MD         
Rigshospitalet Recruiting
København Ø, Denmark, 2100
Contact: Anette Anberg       anette.eva.anberg@regionh.dk   
Principal Investigator: Johannes Klitgaard Jakobsen, MD         
Germany
Charité Campus Mitte Recruiting
Berlin, Germany, 10117
Contact: Eileen Dominick    +49 30 450 560 116    Eileen.dominick@charite.de   
Principal Investigator: Katrin Hahn, MD         
Hannover Medical School Recruiting
Hannover, Germany, 30625
Contact: Chantal Fischer    '+49 (0) 511 532-8333    fischer.chantal@mh-hannover.de   
Principal Investigator: Susanne Petri, MD         
Universitätsklinikum Jena Recruiting
Jena, Germany, 07747
Contact: Julian Grosskreutz, MD    0049 3641 9323488    julian.grosskreutz@med.uni-jena.de   
Principal Investigator: Julian Grosskreutz, MD         
Westfälische Wilhelms-Universität Münster Recruiting
Münster, Germany, 48129
Contact: Angelika Okegwo    0049 251 8348335    Angelika.Okegwo@ukmuenster.de   
Principal Investigator: Peter Young, MD         
Italy
Azienda Ospedaliera di Verona-Policlinico G.B. Rossi Recruiting
Verona, Italy, 37134
Contact: Maria Tozzi       mariachiara.tozzi@ospedaleuniverona.it   
Principal Investigator: Laura Bertolasi, MD         
Netherlands
Academisch Medisch Centrum Recruiting
Amsterdam, Netherlands, 1105 AZ
Contact: Eric Voorn, PhD       e.l.voorn@amc.uva.nl   
Contact: Tamar Gibson    300169184    j.t.gibson@amc.uva.nl   
Principal Investigator: Frans Nollet, MD         
Poland
Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie Recruiting
Krakow, Poland, 31-503
Contact: Jan Banach    0048 12 424 86 00    j.t.banach@gmail.com   
Principal Investigator: Marta Banach, MD         
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Recruiting
Lublin, Poland, 20-954
Contact: Urszula Chyrchel    +48817244720    ullach@poczta.onet.pl   
Principal Investigator: Konrad Rejdak, MD         
Centrum Medyczne HCP Lecznictwo Stacjonarne Recruiting
Poznan, Poland, 61-485
Contact: Karolina Stryczynska-Piasecka    +48618311786    kpe@poczta.onet.pl   
Principal Investigator: Jaroslaw Wronka, MD         
Samodzielny Publiczny Centralny Szpital Kliniczny Recruiting
Warsaw, Poland, 02-097
Contact: Malgorzata Gawel    '48 22 599 28 58    mgawel@wum.edu.pl   
Principal Investigator: Anna Kaminska, MD         
Romania
Spitalul Clinic Colentina Withdrawn
Bucharest, Romania, 020125
Spain
Institut Guttman Cami Can Ruti Recruiting
Barcelona, Spain
Principal Investigator: Enric Portell         
Sweden
Danderyds Sjukhus AB Not yet recruiting
Stockholm, Sweden, 18288
Principal Investigator: Kristian Borg, MD         
Sponsors and Collaborators
Instituto Grifols, S.A.
Investigators
Principal Investigator: Marinos Dalakas Coordinating Investigator
  More Information

Responsible Party: Instituto Grifols, S.A.
ClinicalTrials.gov Identifier: NCT02176863     History of Changes
Other Study ID Numbers: IG1104
First Submitted: June 25, 2014
First Posted: June 27, 2014
Last Update Posted: August 3, 2017
Last Verified: August 2017

Keywords provided by Grifols Biologicals Inc. ( Instituto Grifols, S.A. ):
FORCE
post-polio syndrome
Flebogamma
Immune Globulin Intravenous
IGIV

Additional relevant MeSH terms:
Syndrome
Poliomyelitis
Postpoliomyelitis Syndrome
Disease
Pathologic Processes
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Myelitis
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Spinal Cord Diseases
Neuromuscular Diseases
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neurodegenerative Diseases
Immunoglobulins
Antibodies
gamma-Globulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs