To test whether monthly infusions (every four weeks) of intravenous Flebogamma® 5% DIF in a 1 year treatment period in PPS subjects are superior to placebo by assessing physical performance, as measured by 2MWD.For Stage 1, to select the optimal…
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Brief title
Condition
- Viral infectious disorders
- Spinal cord and nerve root disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Physical performance (2MWD) from baseline to the end of the treatment period
(at End of Treatment Visit [EoTV] * Week 52).
Secondary outcome
To evaluate clinical effect of Flebogamma 5%DIF in PPS subjects by:
- assessing pain, as measured by VAS of pain, compared to that of placebo
- evaluating health-related quality of life (HRQoL), as measured by SF-36 PCS,
compared to that of placebo
- endurance, as measured by 6MWD, compared to that of placebo.
Background summary
Intravenous Immune Globulin (IVIG) is a therapeutic preparation of pooled
polyspecific immune globulin G (IgG) obtained from the plasma of a large number
of healthy blood donors. These preparations were commercialized in the early
1980s to replace intramuscular preparations of polyspecific IgG, which were the
only available substitutive therapy at that time for patients with primary or
secondary immunodeficiencies. IVIG
has been widely available in several indications, has a well-documented safety
profile and, based on the accumulated experience, it has the potential to be of
benefit in patients with post-polio syndrome.
Study objective
To test whether monthly infusions (every four weeks) of intravenous Flebogamma®
5% DIF in a 1 year treatment period in PPS subjects are superior to placebo by
assessing physical performance, as measured by 2MWD.
For Stage 1, to select the optimal dose of IVIG as compared to the placebo.
For Stage 2, to establish superiority of the selected dose of IVIG as compared
to placebo by combining both Stage 1 and Stage 2 data.
Study design
This is a phase II/III multi-centre, 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
in the change in physical performance (Two Minutes Walk Distance [2MWD]) as
compared to placebo and for overall safety analysis in PPS subjects. Other
clinically meaningful outcomes will also be evaluated such as pain,
health-related quality of life (HRQoL), endurance, fatigue, muscle strength,
and walking activity in daily life.
Stage 1 will be a three-arm evaluation of two dose levels of Flebogamma® 5% DIF
(IVIG 1 g/kg and 2 g/kg of body weight) and placebo randomized in a 1:1:1
ratio. At the end of Stage 1 (when at least 80% of the randomized subjects have
finished the treatment period of Stage 1), a formal unblinded interim analysis
will be performed by an independent Data Monitoring Committee (DMC). Based on
pre-defined criteria, one of the doses of Flebogamma® 5% DIF from the two
active treatment groups in Stage 1 will be selected to continue to Stage 2 of
the clinical trial. Subsequently, at Stage 2, a separate cohort of subjects
will be randomized to receive the dose of Flebogamma® 5% DIF selected in Stage
1 or placebo in a 1:1 ratio for efficacy confirmation and overall safety
analysis. During both stages of the study, randomization will be stratified by
the main part of the body affected, that is, lower extremities or upper
extremities.
Both stages, Stage 1 and Stage 2, will consist of a screening period (4 weeks),
a treatment period (52 weeks), and a follow-up period (24 weeks).
Intervention
Subjects will receive intravenous infusions of investigational product (test or
placebo) every 4 weeks during a treatment period of 52 weeks. A window period
of ± 1 week is allowed for any infusion after Infusion 1.
Study burden and risks
Flebogamma is made from human blood, which may contain infectious agents, such
as viruses, that can cause disease. However, the risk that Flebogamma will
transmit an infectious agent has been greatly reduced by 1) screening donors
for prior exposure to certain viruses, 2) testing for the presence of viral
infections and 3) inactivating and/or removing viruses during the manufacturing
process. Despite these safety measures, there is a small chance that such
products could transmit disease. The main risk for getting a disease from
Flebogamma is from infectious agents that cannot yet be detected through the
screening process. The optimal dose and IVIG cycle frequency has not been
examined in PPS, the rationale for the doses, dosage regimen and treatment
period is mainly based on experience in previous clinical trials of IVIG in PPS
and in other inflammatory neuropathies, such as Guillain Barré syndrome (GBS)
or chronic inflammatory demyeliating polyradiculoneuropathy (CIDP), which, as
PPS, is a slowly progressive disease.
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Av. Generalitat 152
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ES
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Age
Inclusion criteria
1. Male or female aged 18 to 75 years.
2. Subjects who understand and voluntarily signed and dated the Clinical Trial
Written Informed Consent Form for his/her clinical trial participation.
3. Subjects with a BMI less than 30 kg/m2.
4. Subjects who meet the clinical criteria for diagnosis of PPS as set by the
March-of-Dimes.
5. 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).
6. Subjects who have at least two newly weakened muscle groups due to PPS (as
defined by medical history), with at least one of them in a lower extremity, as
defined by medical history and having a mMRC scale score of 3 or geater at the
MMT performed by the independent assessor at the SV.
7. Female subjects of child-bearing potential must have a negative test for
pregnancy (human chorionic gonadotropin [HCG]-based assay).
8. Female subjects 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.
9. 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 whole duration of the study.
10. Subjects who are able to walk a 2MWD of at least 50 meters at the Screening
Visit (SV) and EV/IV1.
11. Subjects who are able to walk a consistent baseline 2MWD, that is, the
difference in 2MWD between the SV and EV/IV1 is not more than 10%.
Exclusion criteria
1. Subjects who have received human normal immune globulin treatment given by
intravenous, subcutaneous or intramuscular route within the last 3 years.
2. Subjects who are not ambulatory (wheelchair-bound individuals).
3. Subjects with poor venous access.
4. Subjects with intractable pain requiring narcotics or other psychotropic
drugs.
5. Subjects with a history of anaphylactic reactions or severe reactions to any
blood-derived product.
6. Subjects with a history of intolerance to any component of the
investigational products, such as sorbitol.
7. Subjects who are receiving corticosteroids, except for those who are taking
them for asthma.
8. Subjects with a documented diagnosis of hyperviscosity or hypercoagulable
state or thrombotic complications to polyclonal IVIG therapy in the past.
9. Subjects with a history of recent (within the last year) myocardial
infarction, stroke, or uncontrolled hypertension.
10. Subjects who suffer from congestive heart failure, embolism, or ECG changes
indicative of unstable angina or atrial fibrillation. 11. Subjects with a
history of chronic alcoholism or illicit drug
abuse (addiction) in the preceding 12 months prior to the SV.
12. Subjects with active psychiatric illness that interferes with compliance or
communication with health care personnel.
13. Subjects with depression with scores >30 as assessed by the CESD validated
scale.
14. Females who are pregnant or are nursing an infant child.
15. 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.
16. Subjects currently receiving, or have received within 3 months prior to the
Screening Visit, any investigational medicinal product or device.
17. Subjects who are unlikely to adhere 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.
18. Subjects with a known selective IgA deficiency and serum antibodies
anti-IgA.
19. Subjects with renal impairment (i.e., serum creatinine exceeds more than
1.5 time the upper limit of normal [ULN] for the expected normal range for the
testing laboratory).
20. Subjects with AST or ALT levels exceeding more than 2.5 times the ULN for
the expected normal range for the testing laboratory.
21. Subjects with hemoglobin levels <10 mg/dL, platelets levels <100,000/mm3,
white blood cells count <3.0 k/*L and ESR >50 mm/h or twice above normal.
22. Subjects with known seropositive to HCV, HIV-1 and/or HIV-2.
23. Subjects with a history of intolerance to fructose.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-004503-39-NL |
| ClinicalTrials.gov | NCT02176863 |
| CCMO | NL49498.018.14 |