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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. (see Contacts and Locations)
Verified April 2016 by Grifols Biologicals Inc.
Sponsor:
Information provided by (Responsible Party):
Grifols Biologicals Inc. ( Instituto Grifols, S.A. )
ClinicalTrials.gov Identifier:
NCT02176863
First received: June 25, 2014
Last updated: April 5, 2016
Last verified: April 2016

June 25, 2014
April 5, 2016
July 2014
December 2017   (Final data collection date for primary outcome measure)
Change from baseline in 2MWD [ Time Frame: Baseline, Week 52 ]
Same as current
Complete list of historical versions of study NCT02176863 on ClinicalTrials.gov Archive Site
  • Change from baseline in Visual Analogue Scale (VAS) of pain [ Time Frame: Baseline, Week 52 ]
  • Change from baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) [ Time Frame: Baseline, Week 52 ]
  • Change from baseline in Six Minutes Walk Distance (6MWD) [ Time Frame: Baseline, Week 52 ]
Same as current
  • Muscle Strength of two newly weakened muscle groups (MMT using the MRC scale) [ Time Frame: Baseline, Week 52 ]
  • Muscle strength of two newly weakened muscle groups (QMT using a dynamometer) [ Time Frame: Baseline, Week 52 ]
  • Walking activity in daily life (pedometer) [ Time Frame: Baseline, Week 52 ]
  • Fatigue (FSS) [ Time Frame: Baseline, Week 52 ]
  • HRQoL (SF-36 MCS) [ Time Frame: Baseline, Week 52 ]
  • Blood and CSF (CSF is optional) inflammatory cytokines [ Time Frame: Baseline, Week 52 ]
  • 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.
Not Provided
 
Study of the Efficacy and Safety of Immune Globulin Intravenous (Human) Flebogamma® 5% DIF in Patients With Post-polio Syndrome
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

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.

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.
  • 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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Post-polio Syndrome
  • Biological: Flebogamma 5% DIF
    Human plasma-derived immunoglobulin
    Other Name: immune globulin intravenous (human)
  • Other: Placebo
    Normal saline solution
  • Experimental: 2 g/kg Flebogamma 5% DIF
    Flebogamma 5% DIF, 2 g/kg, intravenous infusion every 4 weeks over two days for 52 weeks
    Intervention: Biological: Flebogamma 5% DIF
  • Experimental: 1 g/kg Flebogamma 5% DIF
    Flebogamma 5% DIF, 1 g/kg, intravenous infusion every 4 weeks over two days for 52 weeks
    Intervention: Biological: Flebogamma 5% DIF
  • Placebo Comparator: Placebo
    Normal Saline Solution, matching volume, intravenous infusion every 4 weeks over two days for 52 weeks
    Intervention: Other: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
210
December 2018
December 2017   (Final data collection date for primary outcome measure)

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.
  • Have at least two newly weakened muscle groups, and one of them in a lower extremity, as defined by medical history and having a mMRC scale score of 3 or greater.
  • 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 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.
Sexes Eligible for Study: All
18 Years to 75 Years   (Adult, Senior)
No
Contact: Sandra Camprubi sandra.camprubi@grifols.com
Contact: Karen Rucker karen.rucker@grifols.com
United States,   Canada,   Denmark,   Germany,   Italy,   Netherlands,   Poland,   Romania,   Spain,   Sweden
 
 
NCT02176863
IG1104
Yes
Not Provided
Not Provided
Not Provided
Instituto Grifols, S.A.
Instituto Grifols, S.A.
Not Provided
Principal Investigator: Marinos Dalakas Coordinating Investigator
Grifols Biologicals Inc.
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP