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

NCT02872142 | Completed Phase 2 Results FDA Drug

• 1 other identifier: GBI1501
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score

  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)

  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 Outcomes (15)

• 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

  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

  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

  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)

  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

  Weeks 25 and 48

Other Outcomes (3)

• Percentage of PE Sessions Associated With at Least One Adverse Reaction (AR)

  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

  During or within 72 hours after the completion of the product infusion

• Incidence of All AEs

  Weeks -2 to 48

Study Arms (1)

Albutein 5%

EXPERIMENTAL

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%; Procedure: Plasma Exchange

Interventions

Albutein 5% BIOLOGICAL

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.

Also known as: Albutein 5% solution for perfusion

Albutein 5%

Plasma Exchange PROCEDURE

Plasma Exchange will be performed using albutein 5% as the replacement solution.

Albutein 5%

Eligibility Criteria

• Age: 19 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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:
• Thrombocytopenia (platelets \<100,000/ microliter \[μL\])
• Fibrinogen \<1.5 gram per liter (g/L)
• International Normalized Ratio \>1.5
• Beta-blocker treatment and bradycardia \<50 beats/min
• 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

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead
• Grifols Biologicals, LLC: collaborator

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Albumins; Solutions; Perfusion; Plasma Exchange

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Proteins; Amino Acids, Peptides, and Proteins; Pharmaceutical Preparations; Investigative Techniques; Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Results Point of Contact

• Title: Michael Woodward
• Organization: Grifols Bioscience Industrial Group

michael.woodward@grifols.com

+34 938008784

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2016
• First Posted: August 19, 2016
• Study Start: August 29, 2016
• Primary Completion: August 15, 2019
• Study Completion: August 15, 2019
• Last Updated: May 5, 2021
• Results First Posted: May 5, 2021

Record last verified: 2021-04

Locations

US (1)