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 Participants With Post-Polio Syndrome
Overview
- Phase
- Phase 2
- Intervention
- Flebogamma® 5% DIF
- Conditions
- Post-polio Syndrome
- Sponsor
- Instituto Grifols, S.A.
- Enrollment
- 191
- Locations
- 21
- Primary Endpoint
- Change From Baseline in Physical Performance Assessed by Two-Minute Walk Distance (2MWD) Test
- Status
- Terminated
- Last Updated
- 4 months ago
Overview
Brief Summary
This was a multicenter, prospective, randomized, placebo-controlled, double-blind, parallel group clinical trial with adaptive dose selection in participants with post-polio syndrome (PPS).
The main purpose of this study was 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 consisted 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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants with Body Mass Index less than 35 kg/m\^
- •Participants who meet the clinical criteria for diagnosis of PPS as set by March-of-Dimes.
- •Participants who are ambulatory or are able to walk with a cane or other aids or use a wheelchair (but they are not wheelchair-bound).
- •Participants 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 a 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.
- •Participants 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.
- •Participants who are able to walk a 2MWD of at least 50 meters at the SV and Enrollment Visit/Infusion Visit 1 (EV/IV1)
- •Participants 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
- •Participants who have received human normal immune globulin treatment given by intravenous, subcutaneous, or intramuscular route within the last 3 years.
- •Participants who are not ambulatory (wheelchair-bound individuals).
- •Participants with poor venous access.
- •Participants with intractable pain requiring narcotics or other psychotropic drugs.
- •Participants with a history of anaphylactic reactions or severe reactions to any blood-derived product.
- •Participants with a history of intolerance to any component of the investigational products, such as sorbitol.
- •Participants receiving corticosteroids, except for those who are taking inhaled corticosteroids for asthma.
- •Participants with a documented diagnosis of hyper viscosity or hypercoagulable state or thrombotic complications to polyclonal intravenous immunoglobulin (IVIG) therapy in the past.
- •Participants with a history of recent (within the last year) myocardial infarction, stroke, or uncontrolled hypertension.
- •Participants who suffer from congestive heart failure, embolism, or electrocardiogram changes indicative of unstable angina or atrial fibrillation.
Arms & Interventions
Stage 1 Arm 1: 2 g/kg Flebogamma® 5% DIF
Participants received Flebogamma® 5% DIF 2 g/kg of body weight administered via intravenous (IV) infusion over 2 consecutive days (Flebogamma® 5% DIF 1 g/kg infused on Day 1, followed by Flebogamma® 5% DIF 1 g/kg infused on Day 2) every 4 weeks for 52 weeks.
Intervention: Flebogamma® 5% DIF
Stage 1 Arm 2: 1 g/kg Flebogamma® 5% DIF
Participants received Flebogamma® 5% DIF 1 g/kg of body weight administered via IV infusion on Day 1, followed by 20 mL/kg of matching placebo 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 Flebogamma® 5% DIF or matching placebo was randomly determined for each participant and was the same for the participant for all infusion visits during the treatment period.
Intervention: Flebogamma® 5% DIF
Stage 1 Arm 2: 1 g/kg Flebogamma® 5% DIF
Participants received Flebogamma® 5% DIF 1 g/kg of body weight administered via IV infusion on Day 1, followed by 20 mL/kg of matching placebo 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 Flebogamma® 5% DIF or matching placebo was randomly determined for each participant and was the same for the participant for all infusion visits during the treatment period.
Intervention: Placebo
Stage 1 Arm 3: Placebo
Participants received matching placebo at a total dose of 40 mL/kg of body weight administered via IV infusion over 2 consecutive days. On Day 1, a dose of 20 mL/kg of matching placebo was given, followed by the second dose of 20 mL/kg of matching placebo on Day 2, administered every 4 weeks for 52 weeks.
Intervention: Placebo
Stage 2 Arm 1: 1 g/kg Flebogamma® 5% DIF
Participants received Flebogamma® 5% DIF 1 g/kg of body weight administered via IV infusion on Day 1, followed by 20 mL/kg of matching placebo 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 Flebogamma® 5% DIF or matching placebo was randomly determined for each participant and was the same for the participant for all infusion visits during the treatment period.
Intervention: Flebogamma® 5% DIF
Stage 2 Arm 1: 1 g/kg Flebogamma® 5% DIF
Participants received Flebogamma® 5% DIF 1 g/kg of body weight administered via IV infusion on Day 1, followed by 20 mL/kg of matching placebo 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 Flebogamma® 5% DIF or matching placebo was randomly determined for each participant and was the same for the participant for all infusion visits during the treatment period.
Intervention: Placebo
Stage 2 Arm 2: Placebo
Participants received matching placebo at a total dose of 40 mL/kg of body weight administered via IV infusion over 2 consecutive days. On Day 1, a dose of 20 mL/kg of matching placebo was given, followed by the second dose of 20 mL/kg of matching placebo on Day 2, administered every 4 weeks for 52 weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in Physical Performance Assessed by Two-Minute Walk Distance (2MWD) Test
Time Frame: Baseline to Week 52
The 2MWD was used to assess physical performance by measuring the distance that a participant can quickly walk at a self-preferred speed on an indoor flat, hard surface 30 m (100-ft) hallway in a period of 2 minutes. A positive change from baseline indicates improvement (i.e. a patient can walk farther). Increase in distance walked (in meters) indicates improvement.
Secondary Outcomes
- Change From Baseline in Pain Using Visual Analogue Scale (VAS) of Pain(Baseline to Week 52)
- Change From Baseline in Health-Related Quality of Life (HRQoL) Assessed by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) Physical Component Summary (PCS)(Baseline to Week 52)
- Change From Baseline in Endurance Assessed by Six-Minute Walk Distance (6MWD) Test(Baseline to Week 52)