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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)

Primary Purpose

Post-polio Syndrome

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Flebogamma 5% DIF

Placebo

About this trial

This is an interventional treatment trial for Post-polio Syndrome focused on measuring FORCE, Post-polio syndrome, Flebogamma, Immune Globulin Intravenous, IVIG

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects with Body Mass Index less than 35 kg/m^2.
Subjects who meet the clinical criteria for diagnosis of PPS as set by March-of-Dimes.
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 Manual Muscle Testing (MMT) performed by the independent assessor at the Screening Visit (SV).
Female of child-bearing potential must have a negative test for pregnancy (Human chorionic gonadotropin (HCG)-based assay).
Female of child-bearing potential and their sexual partners have agreed to practice contraception using a method of proven reliability (i.e., hormonal methods; barrier methods; intrauterine devices methods) to prevent a pregnancy during the course of the clinical trial.
Subjects must be willing to comply with all aspects of the clinical trial protocol, including blood sampling and long-term storage of extra samples for the entire duration of the study.
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 (CESD) 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 Immune globulin A class (IgA) deficiency and serum antibodies anti-IgA.
Subjects with renal impairment (i.e., serum creatinine exceeds more than 1.5 times the upper limit of normal [ULN]) for the expected normal range for the testing laboratory).
Subjects with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 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 (HCV), Human immunodeficiency virus-1 (HIV-1) and/or Human immunodeficiency virus-2 (HIV-2).
Subjects with a history of intolerance to fructose.

Sites / Locations

Washington University
SUNY Upstate Medical University
Thomas Jefferson University Hospital
Medical College of Wisconsin
Montreal Neurological Institute Clinical Research Unit, McGill University
Thomayerova nemocnice, Klinicko-farmakologická jednotka
Aarhus Universitets Hospital-Neurologisk Forskning
Rigshospitalet
Charité Campus Mitte
Hannover Medical School
Universitätsklinikum Jena
Klinik für konservative Orthopädie und des Poliozentrums
Westfälische Wilhelms-Universität Münster
Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)
Academisch Medisch Centrum Amsterdam UMC, Locatie AMC
MedTrials
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
Clinical Research Center Sp. z o.o.
Samodzielny Publiczny Centralny Szpital Kliniczny
Institut Guttman
Hospital Universitari Vall d'Hebron

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Stage 1 Arm 1: 2 g/kg Flebogamma 5% DIF

Stage 1 Arm 2: 1 g/kg Flebogamma 5% DIF

Stage 1 Arm 3: Placebo

Stage 2 Arm 1: Flebogamma 5% DIF

Stage 2 Arm 1: Placebo

Arm Description

Flebogamma 5% DIF 2 g/kg of body weight administered via intravenous infusion over 2 consecutive days (Flebogamma 5% DIF 1 g/kg infused on Day 1 and Flebogamma 5% DIF 1 g/kg infused on Day 2) every 4 weeks for 52 weeks.

Flebogamma 5% DIF 1 g/kg of body weight administered via intravenous infusion on Day 1 and 20 mL/kg of body weight of normal saline solution (equivalent volume of 1 g/kg of body weight Flebogamma® 5% DIF infusions) will also be administered on a separate day, for a total dosing period of 2 consecutive days. every 4 weeks for 52 weeks. The order of 1 g/kg of body weight of Flebogamma® 5% DIF or 20 mL/kg of body weight normal saline solution infused on 2 consecutive days will be randomly determined for each participant by the Interactive Web Response System (IWRS), which will remain the same for the participant for all infusion visits during the treatment period.

Normal saline solution total dose of 40 mL/kg of body weight (equivalent volume of 2 g/kg of body weight Flebogamma® 5% DIF infusions) will be administered over 2 consecutive days. On Day 1, a dose of 20 mL/kg of body weight Normal Saline Solution (equivalent volume of 1 g/kg of body weight Flebogamma® 5% DIF infusions) will be administered and on Day 2, the second dose of 20 mL/kg of body weight. Normal saline solution (equivalent volume of 1 g/kg of body weight Flebogamma® 5% DIF infusions) will be administered, every 4 weeks for 52 weeks.

The dose of Flebogamma® 5% DIF selected from Stage 1 will be administered over 2 consecutive days every 4 weeks for 52 weeks.

Normal saline solution total dose of 40 mL/kg of body weight (equivalent volume of 2 g/kg of body weight Flebogamma® 5% DIF infusions) will be administered over 2 consecutive days. On Day 1, a dose of 20 mL/kg of body weight normal saline solution (equivalent volume of 1 g/kg of body weight Flebogamma® 5% DIF infusions) will be administered and on Day 2, the second dose of 20 mL/kg of body weight normal saline solution (equivalent volume of 1 g/kg of body weight Flebogamma® 5% DIF infusions) will be administered, every 4 weeks for 52 weeks.

Outcomes

Primary Outcome Measures

Change From Baseline in Physical Performance Assessed by Two-Minute Walk Distance (2MWD) Test

Secondary Outcome Measures

Change From Baseline in Pain Using Visual Analogue Scale (VAS) of Pain

Pain scale consists of a 100 mm scale where 100 mm stands for the worst imaginable pain and zero stands for no pain.

Change From Baseline in Health-Related Quality of Life (HRQoL) Assessed by Medical Outcomes Study 36-Item Short-Form Health Survey (SF6) Physical Component Summary (PCS)

Change From Baseline in Endurance Assessed bv Six-Minute Walk Distance (6MWD) Test

Full Information

NCT ID

NCT02176863

First Posted

June 25, 2014

Last Updated

December 21, 2022

Sponsor

Instituto Grifols, S.A.

1. Study Identification

Unique Protocol Identification Number

NCT02176863

Brief Title

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

Acronym

FORCE

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Terminated

Study Start Date

September 23, 2014 (Actual)

Primary Completion Date

November 24, 2022 (Actual)

Study Completion Date

November 24, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Instituto Grifols, S.A.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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 Two-Minute 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 intravenous immunoglobulin (IVIG) 1 g/kg and 2 g/kg of body weight) and placebo randomized in a 1:1:1 ratio. Flebogamma 5% DIF 2 g/kg of body weight will be administered over 2 consecutive days (IVIG 1g/kg on Day 1 and IVIG 1g/kg on Day 2) (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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Post-polio Syndrome

Keywords

FORCE, Post-polio syndrome, Flebogamma, Immune Globulin Intravenous, IVIG

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

191 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Stage 1 Arm 1: 2 g/kg Flebogamma 5% DIF

Arm Type

Experimental

Arm Description

Arm Title

Stage 1 Arm 2: 1 g/kg Flebogamma 5% DIF

Arm Type

Experimental

Arm Description

Arm Title

Stage 1 Arm 3: Placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

Stage 2 Arm 1: Flebogamma 5% DIF

Arm Type

Experimental

Arm Description

The dose of Flebogamma® 5% DIF selected from Stage 1 will be administered over 2 consecutive days every 4 weeks for 52 weeks.

Arm Title

Stage 2 Arm 1: Placebo

Arm Type

Placebo Comparator

Arm Description

Normal saline solution total dose of 40 mL/kg of body weight (equivalent volume of 2 g/kg of body weight Flebogamma® 5% DIF infusions) will be administered over 2 consecutive days. On Day 1, a dose of 20 mL/kg of body weight normal saline solution (equivalent volume of 1 g/kg of body weight Flebogamma® 5% DIF infusions) will be administered and on Day 2, the second dose of 20 mL/kg of body weight normal saline solution (equivalent volume of 1 g/kg of body weight Flebogamma® 5% DIF infusions) will be administered, every 4 weeks for 52 weeks.

Intervention Type

Biological

Intervention Name(s)

Flebogamma 5% DIF

Other Intervention Name(s)

immune globulin intravenous (human)

Intervention Description

Human plasma-derived immunoglobulin

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Normal saline solution

Primary Outcome Measure Information:

Title

Change From Baseline in Physical Performance Assessed by Two-Minute Walk Distance (2MWD) Test

Time Frame

Baseline to Week 52

Secondary Outcome Measure Information:

Title

Change From Baseline in Pain Using Visual Analogue Scale (VAS) of Pain

Description

Pain scale consists of a 100 mm scale where 100 mm stands for the worst imaginable pain and zero stands for no pain.

Time Frame

Baseline to Week 52

Title

Change From Baseline in Health-Related Quality of Life (HRQoL) Assessed by Medical Outcomes Study 36-Item Short-Form Health Survey (SF6) Physical Component Summary (PCS)

Time Frame

Baseline to Week 52

Title

Change From Baseline in Endurance Assessed bv Six-Minute Walk Distance (6MWD) Test

Time Frame

Baseline to Week 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects with Body Mass Index less than 35 kg/m^2. Subjects who meet the clinical criteria for diagnosis of PPS as set by March-of-Dimes. 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 Manual Muscle Testing (MMT) performed by the independent assessor at the Screening Visit (SV). Female of child-bearing potential must have a negative test for pregnancy (Human chorionic gonadotropin (HCG)-based assay). Female of child-bearing potential and their sexual partners have agreed to practice contraception using a method of proven reliability (i.e., hormonal methods; barrier methods; intrauterine devices methods) to prevent a pregnancy during the course of the clinical trial. Subjects must be willing to comply with all aspects of the clinical trial protocol, including blood sampling and long-term storage of extra samples for the entire duration of the study. 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 (CESD) 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 Immune globulin A class (IgA) deficiency and serum antibodies anti-IgA. Subjects with renal impairment (i.e., serum creatinine exceeds more than 1.5 times the upper limit of normal [ULN]) for the expected normal range for the testing laboratory). Subjects with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 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 (HCV), Human immunodeficiency virus-1 (HIV-1) and/or Human immunodeficiency virus-2 (HIV-2). Subjects with a history of intolerance to fructose.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marinos Dalakas

Organizational Affiliation

Coordinating Investigator

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

SUNY Upstate Medical University

City

Syracuse

State/Province

New York

ZIP/Postal Code

13210

Country

United States

Facility Name

Thomas Jefferson University Hospital

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

Facility Name

Medical College of Wisconsin

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53226-3596

Country

United States

Facility Name

Montreal Neurological Institute Clinical Research Unit, McGill University

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H3A 2B4

Country

Canada

Facility Name

Thomayerova nemocnice, Klinicko-farmakologická jednotka

City

Prague

ZIP/Postal Code

Country

Czechia

Facility Name

Aarhus Universitets Hospital-Neurologisk Forskning

City

Aarhus N

ZIP/Postal Code

8200

Country

Denmark

Facility Name

Rigshospitalet

City

København Ø

ZIP/Postal Code

2100

Country

Denmark

Facility Name

Charité Campus Mitte

City

Berlin

ZIP/Postal Code

10117

Country

Germany

Facility Name

Hannover Medical School

City

Hannover

ZIP/Postal Code

30625

Country

Germany

Facility Name

Universitätsklinikum Jena

City

Jena

ZIP/Postal Code

07747

Country

Germany

Facility Name

Klinik für konservative Orthopädie und des Poliozentrums

City

Koblenz

ZIP/Postal Code

56073

Country

Germany

Facility Name

Westfälische Wilhelms-Universität Münster

City

Münster

ZIP/Postal Code

48149

Country

Germany

Facility Name

Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)

City

Verona

ZIP/Postal Code

37124

Country

Italy

Facility Name

Academisch Medisch Centrum Amsterdam UMC, Locatie AMC

City

Amsterdam

ZIP/Postal Code

1105 AZ

Country

Netherlands

Facility Name

MedTrials

City

Krakow

ZIP/Postal Code

31-436

Country

Poland

Facility Name

Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie

City

Lublin

ZIP/Postal Code

20-954

Country

Poland

Facility Name

Clinical Research Center Sp. z o.o.

City

Poznan

ZIP/Postal Code

60-848

Country

Poland

Facility Name

Samodzielny Publiczny Centralny Szpital Kliniczny

City

Warsaw

ZIP/Postal Code

02-097

Country

Poland

Facility Name

Institut Guttman

City

Badalona

ZIP/Postal Code

08916

Country

Spain

Facility Name

Hospital Universitari Vall d'Hebron

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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