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



Sponsors


Source

Grifols Biologicals Inc.

Oversight Info

Has Dmc

Yes


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.

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.

Overall Status

Recruiting

Start Date

2014-07-01

Completion Date

2020-09-01

Primary Completion Date

2017-12-01

Phase

Phase 2/Phase 3

Study Type

Interventional

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary Outcome

Measure

Time Frame

Change from baseline in 2MWD
Baseline, Week 52

Secondary Outcome

Measure

Time Frame

Change from baseline in Visual Analogue Scale (VAS) of pain
Baseline, Week 52
Change from baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS)
Baseline, Week 52
Change from baseline in Six Minutes Walk Distance (6MWD)
Baseline, Week 52

Enrollment

210

Condition


Intervention

Intervention Type

Biological

Intervention Name


Description

Human plasma-derived immunoglobulin

Arm Group Label

2 g/kg Flebogamma 5% DIF

1 g/kg Flebogamma 5% DIF


Other Name

immune globulin intravenous (human)


Intervention Type

Other

Intervention Name


Description

Normal saline solution

Arm Group Label

Placebo



Eligibility

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.

Gender

All

Minimum Age

18 Years

Maximum Age

75 Years

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Marinos Dalakas
Principal Investigator
Coordinating Investigator

Overall Contact

Last Name

Sandra Camprubi

Email



Location

Facility

Status

Contact

Investigator

University of California
Los Angeles California 90095 United States
Recruiting
Last Name: Aaron Fisher
Phone: 310-206-8153
Email: [email protected]
Last Name: Susan Perlman, MD
Role: Principal Investigator
Washington University
Saint Louis Missouri 63110 United States
Completed
SUNY Upstate Medical University
Syracuse New York 13210 United States
Recruiting
Last Name: Alisha Hartwell
Phone: 315-464-9756
Email: [email protected]
Last Name: Burke Jubelt, MD
Role: Principal Investigator
Thomas Jefferson University Hospital
Philadelphia Pennsylvania 19107 United States
Recruiting
Last Name: Lauren E Fedor
Phone: 215-955-4663
Email: [email protected]
Last Name: Marinos Dalakas
Role: Principal Investigator
Montreal Neurological Institute, McGill University
Montreal Quebec H3A 2B4 Canada
Recruiting
Last Name: Claire Magnussen, PhD
Phone: 5143983729
Email: [email protected]
Last Name: Daria Trojan, MD
Role: Principal Investigator
Aarhus Universitets Hospital
Aarhus C 8000 Denmark
Recruiting
Last Name: Charlotte G Odgaard
Email: [email protected]
Last Name: Henning Andersen, MD
Role: Principal Investigator
Rigshospitalet
København Ø 2100 Denmark
Recruiting
Last Name: Anette Anberg
Email: [email protected]
Last Name: Johannes Klitgaard Jakobsen, MD
Role: Principal Investigator
Charité Campus Mitte
Berlin 10117 Germany
Recruiting
Last Name: Agata Mossakowski, MD
Phone: +49 30 450560116
Email: [email protected]
Last Name: Katrin Hahn, MD
Role: Principal Investigator
Hannover Medical School
Hannover 30625 Germany
Recruiting
Last Name: Chantal Fischer
Phone: '+49 (0) 511 532-8333
Email: [email protected]
Last Name: Susanne Petri, MD
Role: Principal Investigator
Universitätsklinikum Jena
Jena 07747 Germany
Recruiting
Last Name: Julian Grosskreutz, MD
Phone: 0049 3641 9323488
Email: [email protected]
Last Name: Julian Grosskreutz, MD
Role: Principal Investigator
Westfälische Wilhelms-Universität Münster
Münster 48129 Germany
Recruiting
Last Name: Matthias Boentert
Phone: +49 251 8344403
Email: [email protected]
Last Name: Peter Young, MD
Role: Principal Investigator
Azienda Ospedaliera di Verona-Policlinico G.B. Rossi
Verona 37134 Italy
Recruiting
Last Name: Maria C Tozzi
Email: [email protected]
Last Name: Laura Bertolasi, MD
Role: Principal Investigator
Academisch Medisch Centrum
Amsterdam 1105 AZ Netherlands
Recruiting
Last Name: Eric Voorn, PhD
Email: [email protected]
Last Name: Frans Nollet, MD
Role: Principal Investigator
Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
Krakow 31-503 Poland
Recruiting
Last Name: Jan Banach
Phone: 0048 12 424 86 00
Email: [email protected]
Last Name: Marta Banach, MD
Role: Principal Investigator
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
Lublin 20-954 Poland
Recruiting
Last Name: Urszula Chyrchel
Phone: +48817244720
Email: [email protected]
Last Name: Konrad Rejdak, MD
Role: Principal Investigator
Jaroslaw Wronka
Poznan 61-485 Poland
Recruiting
Last Name: Jaroslaw Wronka, MD
Email: [email protected]
Last Name: Jaroslaw Wronka, MD
Role: Principal Investigator
Samodzielny Publiczny Centralny Szpital Kliniczny
Warsaw 02-097 Poland
Recruiting
Last Name: Malgorzata Gawel
Phone: '48 22 599 28 58
Email: [email protected]
Last Name: Anna Kaminska, MD
Role: Principal Investigator
Spitalul Clinic Colentina
Bucharest 020125 Romania
Withdrawn
Institut Guttman Cami Can Ruti
Barcelona Spain
Recruiting
Last Name: Maria del Pilar Sainz
Email: [email protected]
Last Name: Enric Portell
Role: Principal Investigator
Danderyds Sjukhus AB
Stockholm 18288 Sweden
Not yet recruiting
Last Name: Kristian Borg, MD
Phone: +4686555257
Email: [email protected]
Last Name: Kristian Borg, MD
Role: Principal Investigator

Location Countries

Country

Canada

Denmark

Germany

Italy

Netherlands

Poland

Romania

Spain

Sweden

United States



Verification Date

2017-12-01

Lastchanged Date

2017-12-11

Firstreceived Date

2014-06-25

Responsible Party

Responsible Party Type

Sponsor


Keywords


Is Fda Regulated

Yes

Has Expanded Access

No

Condition Browse


Number Of Arms

3

Intervention Browse

Mesh Term

Immunoglobulins

Antibodies

gamma-Globulins

Immunoglobulins, Intravenous

Rho(D) Immune Globulin



Is Section 801

Yes

Arm Group

Arm Group Label

2 g/kg Flebogamma 5% DIF

Arm Group Type

Experimental

Description

Flebogamma 5% DIF, 2 g/kg, intravenous infusion every 4 weeks over two days for 52 weeks


Arm Group Label

1 g/kg Flebogamma 5% DIF

Arm Group Type

Experimental

Description

Flebogamma 5% DIF, 1 g/kg, intravenous infusion every 4 weeks over two days for 52 weeks


Arm Group Label

Placebo

Arm Group Type

Placebo Comparator

Description

Normal Saline Solution, matching volume, intravenous infusion every 4 weeks over two days for 52 weeks



Firstreceived Results Date

N/A

Overall Contact Backup

Last Name

Karen Rucker

Email



Acronym

FORCE

Other Outcome

Measure

Muscle Strength of two newly weakened muscle groups (MMT using the MRC scale)

Time Frame

Baseline, Week 52

Description

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.


Measure

Muscle strength of two newly weakened muscle groups (QMT using a dynamometer)

Time Frame

Baseline, Week 52

Description

Muscle strength of 2 newly weakened muscle groups (Quantitative Muscle Testing [QMT] using a dynamometer) from baseline to the end of the treatment period.


Measure

Walking activity in daily life (pedometer)

Time Frame

Baseline, Week 52

Description

Walking activity in daily life (pedometer)


Measure

Subject's self-perceived exertion/fatigue level using the Borg scale

Time Frame

Baseline, Week 52

Description

Subject's self-perceived exertion/fatigue level using the Borg scale


Measure

Fatigue (FSS)

Time Frame

Baseline, Week 52

Description

Fatigue (FSS)


Measure

HRQoL (SF-36 MCS)

Time Frame

Baseline, Week 52

Description

HRQoL (SF-36 MCS)


Measure

Blood and CSF (CSF is optional) inflammatory cytokines

Time Frame

Baseline, Week 52

Description

Blood and CSF (CSF is optional) inflammatory cytokines


Measure

Sustained effect of Flebogamma 5% DIF compared to placebo

Time Frame

Baseline, Week 76

Description

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.



Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary Purpose

Treatment

Masking

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)


Study First Submitted

June 25, 2014

Study First Submitted Qc

June 25, 2014

Study First Posted

June 27, 2014

Last Update Submitted

December 11, 2017

Last Update Submitted Qc

December 11, 2017

Last Update Posted

December 13, 2017


ClinicalTrials.gov processed this data on December 13, 2017

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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