Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
 
ClinicalTrials.gov Identifier: NCT02176863
Recruitment Status : Recruiting
First Posted : June 27, 2014
Last Update Posted : August 20, 2020
Sponsor:
Collaborator:
Instituto Grifols, S.A.
Information provided by (Responsible Party):
Grifols Therapeutics LLC

Tracking Information
First Submitted Date  ICMJE June 25, 2014
First Posted Date  ICMJE June 27, 2014
Last Update Posted Date August 20, 2020
Actual Study Start Date  ICMJE September 23, 2014
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 15, 2018)
Change from baseline in 2MWD [ Time Frame: Baseline to Week 52 ]
Physical performance (2MWD) from baseline (at Enrollment Visit) to the end of the treatment period
Original Primary Outcome Measures  ICMJE
 (submitted: June 25, 2014)
Change from baseline in 2MWD [ Time Frame: Baseline, Week 52 ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2014)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Efficacy and Safety of Immune Globulin Intravenous (Human) Flebogamma® 5% DIF in Patients With Post-polio Syndrome
Official Title  ICMJE 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
Brief Summary

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.

The study will consist of 2 stages, with each stage consisting of a screening period (up to 4 weeks), a treatment period (52 weeks), and a follow-up period (24 weeks).

Detailed Description

This is a phase II/III multicenter, 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. Stage 1 is a 3-arm evaluation of 2 dose levels of Flebogamma 5% DIF. Flebogamma 5% DIF 2 g/kg of body weight (IVIG 2 g/kg arm), 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), or a total dose of 40 mL/kg of body weight Normal Saline Solution (equivalent volume of the 2 g/kg of body weight Flebogamma 5% DIF infusions) (placebo arm) will be administered over 2 consecutive days every 4 weeks during a 52-week treatment period. At the end of Stage 1, an interim analysis will be conducted and 1 of the 2 Flebogamma 5% DIF doses will be selected based on predefined criteria to be used for Stage 2.

Stage 2 will consist of 2 treatment arms, the selected dose of Flebogamma 5% DIF from Stage 1 and Normal Saline Solution (40 mL/kg of body weight). Study drug will be administered over 2 consecutive days every 4 weeks 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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Post-polio Syndrome
Intervention  ICMJE
  • Biological: Flebogamma 5% DIF
    Human plasma-derived immunoglobulin
    Other Name: immune globulin intravenous (human)
  • Other: Placebo
    Normal saline solution
Study Arms  ICMJE
  • Experimental: Stage 1 Arm 1: 2 g/kg Flebogamma 5% DIF
    Flebogamma 5% DIF 2 g/kg body weight administered via intravenous infusion over 2 consecutive days (1 g/kg infused on Day 1 and 1 g/kg infused on Day 2) every 4 weeks for 52 weeks
    Intervention: Biological: Flebogamma 5% DIF
  • Experimental: Stage 1 Arm 2: 1 g/kg Flebogamma 5% DIF
    Flebogamma 5% DIF 1 g/kg body weight administered via intravenous infusion on Day 1 every 4 weeks for 52 weeks
    Intervention: Biological: Flebogamma 5% DIF
  • Placebo Comparator: Stage 1 Arm 3: Placebo
    Normal Saline Solution of matching volume, administered via intravenous infusion either over 1 day or 2 consecutive days every 4 weeks for 52 weeks
    Intervention: Other: Placebo
  • Experimental: Stage 2 Arm 1: Flebogamma 5% DIF
    The dose of Flebogamma® 5% DIF selected from Stage 1 will be administered every 4 weeks over 2 consecutive days during a 52-week treatment period.
    Intervention: Biological: Flebogamma 5% DIF
  • Placebo Comparator: Stage 2 Arm 1: Placebo
    A total dose of 40 mL/kg of body weight of Normal Saline Solution will be administered over 2 consecutive days (20 mL/kg infused on Day 1 and 20 mL/kg infused on Day 2).
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 25, 2014)
210
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects with Body Mass Index less than 35 kg/m^2.
  • Subjects meet March-of-Dimes clinical criteria for diagnosis of PPS.
  • Subjects who are 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 Medical Research Council (MRC) scale score greater than 3 at the MMT performed by the independent assessor at the Screening Visit (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.
  • Subjects who are able to walk a 2MWD of at least 50 meters at the SV and Enrollment Visit/Infusion Visit 1 (EV/IV1)
  • 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:

  • Subjects have received human normal immune globulin treatment given by intravenous, subcutaneous, or intramuscular route within the last 3 years.
  • Subjects who are not ambulatory (wheelchair-bound individuals).
  • Subjects with poor venous access.
  • Subjects with intractable pain requiring narcotics or other psychotropic drugs.
  • Subjects with a history of anaphylactic reactions or severe reactions to any blood-derived product.
  • Subjects with a history of intolerance to any component of the investigational products, such as sorbitol.
  • Subjects receiving corticosteroids, except for those who are taking inhaled corticosteroids for asthma.
  • Subjects with a documented diagnosis of hyperviscosity or hypercoagulable state or thrombotic complications to polyclonal intravenous immunoglobulin (IVIG) therapy in the past.
  • Subjects with a history of recent (within the last year) myocardial infarction, stroke, or uncontrolled hypertension.
  • Subjects who suffer from congestive heart failure, embolism, or electrocardiogram changes indicative of unstable angina or atrial fibrillation.
  • Subjects with a history of chronic alcoholism or illicit drug abuse (addiction) in the preceding 12 months prior to the SV.
  • Subjects with active psychiatric illness that interferes with compliance or communication with health care personnel.
  • Subjects with 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.
  • Subjects with any medical condition which makes clinical trial participation unadvisable or which is likely to interfere with the evaluation of the study treatment and/or the satisfactory conduct of the clinical trial according to the Investigator's judgment.
  • Subjects currently receiving, or have received within 3 months prior to the SV, any investigational medicinal product or device.
  • Subjects who are unlikely to adhere to the protocol requirements, or are likely to be uncooperative, or unable to provide a storage serum/plasma sample prior to the first investigational drug infusion.
  • Subjects with known selective IgA deficiency and serum antibodies anti-IgA.
  • Subjects with 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.
  • Subjects with hemoglobin levels <10 g/dL, platelets levels <100,000/mm^3, white blood cells count <3.0 k/µL, and erythrocyte sedimentation rate >50 mm/h or twice above normal.
  • Subjects with known seropositive to Hepatitis C virus, Human immunodeficiency virus-1 and/or Human immunodeficiency virus-2.
  • Subjects with a history of intolerance to fructose.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sandra Camprubi sandra.camprubi@grifols.com
Contact: Karen Rucker karen.rucker@grifols.com
Listed Location Countries  ICMJE Canada,   Czechia,   Denmark,   France,   Germany,   Hungary,   Ireland,   Italy,   Netherlands,   Poland,   Romania,   Spain,   Sweden,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02176863
Other Study ID Numbers  ICMJE IG1104
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Grifols Therapeutics LLC
Study Sponsor  ICMJE Grifols Therapeutics LLC
Collaborators  ICMJE Instituto Grifols, S.A.
Investigators  ICMJE
Principal Investigator: Marinos Dalakas Coordinating Investigator
PRS Account Grifols Therapeutics LLC
Verification Date August 2020

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