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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)

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ClinicalTrials.gov Identifier: NCT02176863
Recruitment Status : Recruiting
First Posted : June 27, 2014
Last Update Posted : November 19, 2018
Sponsor:
Collaborator:
Instituto Grifols, S.A.
Information provided by (Responsible Party):
Grifols Therapeutics LLC

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).


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

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), 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 2 consecutive days during a 52-week treatment period. At the end of Stage 2, 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 every 4 weeks over 2 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).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 210 participants
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
Actual Study Start Date : September 23, 2014
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : June 2021


Arm Intervention/treatment
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
Biological: Flebogamma 5% DIF
Human plasma-derived immunoglobulin
Other Name: immune globulin intravenous (human)

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
Biological: Flebogamma 5% DIF
Human plasma-derived immunoglobulin
Other Name: immune globulin intravenous (human)

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
Other: Placebo
Normal saline solution

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.
Biological: Flebogamma 5% DIF
Human plasma-derived immunoglobulin
Other Name: immune globulin intravenous (human)

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).
Other: Placebo
Normal saline solution




Primary Outcome Measures :
  1. 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



Information from the National Library of Medicine

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

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.

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

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Sponsors and Collaborators
Grifols Therapeutics LLC
Instituto Grifols, S.A.
Investigators
Principal Investigator: Marinos Dalakas Coordinating Investigator

Responsible Party: Grifols Therapeutics LLC
ClinicalTrials.gov Identifier: NCT02176863     History of Changes
Other Study ID Numbers: IG1104
First Posted: June 27, 2014    Key Record Dates
Last Update Posted: November 19, 2018
Last Verified: November 2018

Keywords provided by Grifols Therapeutics LLC:
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