Efficacy and Safety of Plasma Exchange With Albutein® 5% in Participants With Amyotrophic Lateral Sclerosis

April 9, 2021 updated by: Grifols Therapeutics LLC

Pilot Study to Evaluate the Efficacy and Safety of Plasma Exchange With Albutein® 5% in Patients With Amyotrophic Lateral Sclerosis

This is a pilot, phase 2, prospective, open-label, single-arm study to evaluate disease progression, forced vital capacity, and the safety and tolerability of plasma exchange (PE) using Albutein® 5% in participants with amyotrophic lateral sclerosis (ALS).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a phase 2, prospective, open-label, single-arm pilot study to evaluate the efficacy and safety of PE with Albutein® 5% in participants with ALS. The planned enrollment is 10 participants who have a definite, possible, or probable diagnosis of ALS, according to the revised El Escorial criteria. Enrolled participants will be treated with PE using Albutein 5% as a replacement solution during an Intensive Treatment Phase (2 PEs per week over 3 weeks) followed by a Maintenance Treatment Phase (weekly PE for 21 weeks) for a total treatment duration of 6 months. A 6-month follow up will begin after the last PE.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth-Hitchcock Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

19 years to 69 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Signed informed consent
  • Subjects over 18 years of age and less than 70 years old
  • Subjects with a possible, probable-lab supported, probable, or definite diagnosis of Amyotrophic Lateral Sclerosis (ALS), according to the revised El Escorial criteria
  • Subjects having experienced their first ALS symptoms within 18 months prior to recruitment/consent
  • Forced Vital Capacity > 70%
  • Subjects must be medically suitable for study participation and willing to comply with all planned aspects of the protocol, including blood sampling, at the time of inclusion in the study.

Exclusion Criteria:

  • Subjects with pre-existing clinically significant lung disease not attributable to ALS
  • Subjects diagnosed with other neurodegenerative diseases or diseases associated with other motor neuron dysfunction
  • Participation in another investigational product study within one month prior to screening
  • Females who are pregnant, breastfeeding, or, if of child-bearing potential, unwilling to practice a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, condom or occlusive cap with spermicidal foam/ gel/ film/ cream/ suppository, male sterilization, or true abstinence) throughout the study
  • Difficult or problematic peripheral vein access and inability to implant a central catheter which would make continuous Plasma exchange (PE) not feasible as per the visit protocol

  • Contraindication to undergo PE or subject has abnormal coagulation parameters at the discretion of the Outpatient Apheresis Unit team, including but not limited to:

    1. Thrombocytopenia (platelets <100,000/ microliter [μL])
    2. Fibrinogen <1.5 gram per liter (g/L)
    3. International Normalized Ratio >1.5
    4. Beta-blocker treatment and bradycardia <50 beats/min
    5. Treatment with angiotensin-converting enzyme inhibitors which may increase the risk of allergic reactions, unless a preventive change in hypotensive treatment occurs prior to enrollment
  • History of anaphylaxis or severe systemic response to any plasma-derived albumin preparation, component of Albutein® 5%, or other blood product(s)
  • Subjects unable to interrupt treatment with acetylsalicylic acid, other oral antiplatelet, or anticoagulant
  • Renal dysfunction by elevated creatinine concentration >2 milligram per deciliter (mg/dL)
  • Presence of heart disease that contraindicates PE treatment, including ischemic cardiopathy and congestive heart failure
  • Presence of prior behavioural disorders requiring pharmacological intervention with less than 3 months of stable treatment
  • Mentally challenged subject who cannot give independent informed consent
  • Any condition that would complicate compliance with the study protocol (i.e., illness with the expectation of less than one year survival, abuse of drugs or alcohol, etc.)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Albutein 5%
Plasma exchanges (PEs) with albutein 5% as a replacement solution during an intensive treatment phase of two PEs per week over 3 weeks followed by maintenance treatment phase of weekly PE for 21 weeks. The dose of albutein 5% for replacement following plasma removal was calculated based on gender, weight, and the hematocrit of the participant.
Biological: Albutein 5%
Albutein is manufactured from human plasma. The dose of Albutein 5% for replacement following plasma removal will be calculated based on gender, weight, and the hematocrit of the participant.
Other Names:
  • Albutein 5% solution for perfusion
Procedure: Plasma Exchange
Plasma Exchange will be performed using albutein 5% as the replacement solution.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score
Time Frame: Baseline (Week 0), Weeks 4, 12, 25, 36, and 48
The ALSFRS-R includes 12 questions to assess the self-sufficiency of participants in 3 sub-domains: bulbar function (questions 1-3), fine and gross motor function (questions 4-9), and respiratory function (question 10-12). Aspects of nourishment, personal care, personal autonomy, and communication were also evaluated. Each task was graded on a five-point scale from 0 (incapable) to 4 (normal ability), with total score range from 0 (worst) to 48 (best). A positive change from Baseline indicates improvement.
Baseline (Week 0), Weeks 4, 12, 25, 36, and 48
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC)
Time Frame: Baseline (Week 0), Weeks 4, 12, 25, 36, and 48
The FVC measured the volume of air that can forcibly be exhaled through a spirometer after a full inspiration. It was expressed in a percentage of actual FVC over the expected FVC result in the general population, calculated as: Percent predicted FVC (in %) = [(observed FVC in liters)/(predicted FVC in liters)]*100.
Baseline (Week 0), Weeks 4, 12, 25, 36, and 48

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Cognitive Function as Assessed by Behaviour Status Sub-scale Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioural Screen (ALS-CBS) Test
Time Frame: Baseline (Week 0), Weeks 25, and 48
ALS-CBS test is composed of two sections: the cognitive screening section and behavioural changes section. The section of behavioural changes consists of behaviour status and symptom status sub-scales. Behaviour status sub-scale consists of a questionnaire with 15 items assessed by the caretaker. Each item was scored on a scale ranging from 0 (worst) to 3 (best) yielding a total 0= large changes to 45= no changes. A positive change from Baseline indicates improvement.
Baseline (Week 0), Weeks 25, and 48
Change From Baseline in Cognitive Function as Assessed by Symptom Status Sub-scale Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test
Time Frame: Baseline (Week 0), Weeks 25, and 48
ALS-CBS test is composed of two sections: cognitive screening section and behavioural changes section. The section of behavioural changes consists of behaviour status and symptom status sub-scales. Cognitive function assessed by symptom status sub-scale is reported, which consists of 4 additional questions related to current behavioural symptoms (depression, anxiety, fatigue, and emotional liability). Each question was scored as 0= the presence of symptoms and 1= no current symptoms, giving a total subscale score between 0 and 4. A positive change from Baseline indicates improvement.
Baseline (Week 0), Weeks 25, and 48
Change From Baseline in Cognitive Function as Assessed by Cognitive Screening Section Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test
Time Frame: Baseline (Week 0), Weeks 25, and 48
ALS-CBS test is composed of two sections: cognitive screening section and behavioural changes section. Cognitive function is evaluated using cognitive screening section which consists of: attention (complex orders, mental sums, language, and eye movement); concentration (inversion of numeric series); follow-up and monitoring (reverse sequences, alphabet, number and letter sequencing); and initiation and recovery (nomination). The individual items were scored from 0-5, and the total score ranges from 0-20, where 0= cognitive impairment, 20= no apparent cognitive impairment. A positive change from baseline indicates improvement.
Baseline (Week 0), Weeks 25, and 48
Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG)
Time Frame: Baseline (Week 0), Weeks 4, 12, 25, 36, and 48
Surface EMG was performed to record motor evoked potential in the distal muscles of the upper limbs (thenar and hypothenar eminence) and dorsiflexor muscles of the lower limbs (anterior tibialis) after electrical stimulation on the median, ulnar, and external popliteal sciatic nerve. The data for motor evoked potential (in millivolt [mv]) is reported for thenar muscles of both upper limbs and hypothenar muscle of the upper right limb and anterior tibialis of the both lower limbs.
Baseline (Week 0), Weeks 4, 12, 25, 36, and 48
Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score
Time Frame: Weeks 25 and 48
The ALS questionnaire consists of 40 items grouped into 5 representative dimensions associated with quality of life. The first four dimensions were: physical mobility (questions 1-10), activities of daily living (questions 11- 20), food and drink (questions 21-23), communication (questions 24-30) and emotional function (questions 31-40), refer to deficits and subsequent disabilities as a result of the disease. The fifth scale (emotional functioning) reflects how the participant is facing his/her physical deterioration emotionally. Each item is scored from 0 to 4 according to a gradation of symptom onset frequency (never, rarely, sometimes, often, always). From raw scores, an index from 0 to 100 is obtained for each dimension, which make comparisons with the other dimensions possible as well as a straightforward interpretation of the results (0 = better state of health as measured by the questionnaire;100 = poorer state of health). A negative change from Baseline indicates improvement.
Weeks 25 and 48
Change From Baseline in Plasma Human Apolipoprotein Levels
Time Frame: Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
The levels of human Apolipoprotein (ApoE) in plasma were measured by enzyme-linked immunosorbent assay (ELISA).
Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
Change From Baseline in Plasma Cytokine Panel Levels
Time Frame: Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
The plasma cytokine panel includes: transforming growth factor (TGF) beta1, TGF beta2, TGF beta3, interferon (IFN) gamma, interleukins (IL)-1beta, IL-1Ra, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IFN-γ-inducible protein (IP)-10, human monocyte chemoattractant protein (MCP)-1, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1-alpha, MIP-1-beta, tumor necrosis factor (TNF)-alpha, soluble cluster of differentiation (CD) 40 ligand (sCD40L), fractalkine. The level of each of these cytokines are reported as categories. Only categories with values above the level of detection are reported.
Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
Change From Baseline in Cerebrospinal Fluid (CSF) Human Apolipoprotein Levels
Time Frame: Baseline (Week 0), Weeks 12, and 25
The levels of human Apolipoprotein (ApoE) in CSF were measured by enzyme-linked immunosorbent assay (ELISA).
Baseline (Week 0), Weeks 12, and 25
Change From Baseline in CSF Cytokine Panel Levels
Time Frame: Baseline (Week 0), Weeks 12, and 25
The CSF cytokine panel includes: TGF beta1, TGF beta2, TGF beta3, IFN gamma, IL-1beta, IL-1Ra, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IP-10, MCP-1, MDC, MIP-1 alpha, MIP-1 beta, TNF alpha, sCD40L, fractalkine. The level of each of these cytokines are reported as categories. Only categories with values above the level of detection are reported.
Baseline (Week 0), Weeks 12, and 25
Change From Baseline in Plasma Beta-methylamino-L-alanine (BMAA) Levels
Time Frame: Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
Plasma BMAA levels at baseline and over the course of treatment at each evaluation visit were measured to identify reductions in BMAA levels, which could potentially be correlated with disease progression or a halt in disease progression. Analysis was performed using a Thermo TSQ Quantiva triple-stage quadrupole mass spectrometer.
Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
Change From Cerebrospinal Fluid (CSF) Beta-methylamino-L-alanine (BMAA) Levels
Time Frame: Baseline (Week 0), Weeks 12, and 25
CSF BMAA levels at baseline and over the course of treatment at each evaluation visit were measured to identify reductions in BMAA levels, which could potentially be correlated with disease progression or a halt in disease progression. Analysis was performed using a Thermo TSQ Quantiva triple quadrupole mass spectrometer.
Baseline (Week 0), Weeks 12, and 25
Change From Baseline in Absolute Leukocyte Count
Time Frame: Baseline, Weeks 4, 12, and 48
The immune population profile in ALS participants was assessed by flow cytometry following whole blood staining by Western Blot (WB) for the absolute leukocyte count. Absolute leukocyte count (10^3 cells/microliter) was analyzed for neutrophils, lymphocytes, CD14+ monocytes, CD3+CD4+ T cells, CD3+CD8+ T cells, CD19+ B cells and CD56+ natural killer (NK) cells.
Baseline, Weeks 4, 12, and 48
Change From Baseline in Immune Population Profile
Time Frame: Baseline, Weeks 4, 12, and 48
The immune population profile includes: Leukocyte panel (neutrophils, lymphocytes, CD14+ monos, CD3+CD4+ T cells, CD3+CD8+ T cells, CD19+ B cells, CD56+ NK cells). Regulatory T cells (Treg panel) (CD4+FoxP3+CD127low/, CD4+FoxP3+CD127low/-CD39+, CD4+FoxP3+CD127low/-CD45RA, CD4+FoxP3+CD127low/-CD152+), Myeloid-Derived Suppressor Cells (MDSC) (panel: CD14+CD15- monocytic MDSCs, CD14+CD15- monocytic MDSCs, CD124+ monocytic MDSCs, CD14-CD15+ granulocytic MDSCs, CD124+ granulocytic MDSCs, CD14-CD15- immature MDSCs, CD124+ immature MDSCs), Monocyte panel (CD14+CD16+, CD14+human leukocyte antigen-D related (HLA-DR)+ CD11b, CD14+HLA-DR+ CD163+, CD14+HLA-DR+ CX3CR1+). Data for each of these were reported as categories. Only categories with values above the level of detection are reported.
Baseline, Weeks 4, 12, and 48
Change From Baseline in Plasma Neurofilament Levels
Time Frame: Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
Levels of neurofilaments: Phosphorylated Neurofilament heavy chain (pNF-H) and Neurofilament light chain (NF-L) were measured by Enzyme-Linked Immunosorbent Assay (ELISA).
Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
Change From Baseline in Cerebrospinal Fluid (CSF) Neurofilament Levels
Time Frame: Baseline (Week 0), Weeks 12, and 25
Levels of neurofilaments: Phosphorylated Neurofilament heavy chain (pNF-H) and Neurofilament light chain (NF-L) were measured by Enzyme-Linked Immunosorbent Assay (ELISA).
Baseline (Week 0), Weeks 12, and 25

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
Percentage of PE Sessions Associated With at Least One Adverse Reaction (AR)
Time Frame: During or within 72 hours after the completion of the product infusion
During or within 72 hours after the completion of the product infusion
Percentage of PE Sessions Associated With at Least One Adverse Event (AE), Irrespective of Causality
Time Frame: During or within 72 hours after the completion of the product infusion
During or within 72 hours after the completion of the product infusion
Incidence of All AEs
Time Frame: Weeks -2 to 48
Weeks -2 to 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Grifols Therapeutics LLC

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Grifols Biologicals, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 29, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 15, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 15, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 11, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 15, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 19, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 5, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 9, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GBI1501

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Amyotrophic Lateral Sclerosis

Clinical Trials on Albutein 5%

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings