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

• ClinicalTrials.gov Identifier: NCT02872142
• Recruitment Status: Completed
• First Posted: August 19, 2016
• Last Update Posted: March 13, 2020
• Sponsor: Grifols Therapeutics LLC
• Collaborator: Grifols Biologicals, LLC
• Information provided by (Responsible Party): Grifols Therapeutics LLC

Study Description

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 subjects with amyotrophic lateral sclerosis (ALS).

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Biological: Albutein 5%	Phase 2

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 subjects with ALS. The planned enrollment is 10 subjects who have a definite, possible, or probable diagnosis of ALS, according to the revised El Escorial criteria. Enrolled subjects 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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study to Evaluate the Efficacy and Safety of Plasma Exchange With Albutein® 5% in Patients With Amyotrophic Lateral Sclerosis
• Actual Study Start Date: August 29, 2016
• Actual Primary Completion Date: August 2019
• Actual Study Completion Date: August 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Albutein 5%; Plasma exchanges with Albutein 5% as a replacement solution	Biological: Albutein 5%; Plasma exchange will be performed using Albutein 5% as the replacement solution. 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 subject.; Other Name: Albutein 5% solution for perfusion

Outcome Measures

Primary Outcome Measures :

1. Changes from baseline in the ALS Functional Rating Scale - Revised [ Time Frame: Weeks 0 to 48 ]
2. Changes from baseline in forced vital capacity [ Time Frame: Weeks 0 to 48 ]

Secondary Outcome Measures :

1. Changes from baseline in cognitive function determined by the ALS - Cognitive Behavioral Screen test [ Time Frame: Weeks 0 to 48 ]
2. Changes from baseline in the motor evoked potential in thenar and hypothenar eminence and anterior tibialis muscle determined by electromyography [ Time Frame: Weeks 0 to 48 ]
3. Evaluation of quality of life using the ALS Assessment Questionnaire 40 [ Time Frame: Weeks 0 to 48 ]
4. Changes from baseline in plasma human apolipoproteins [ Time Frame: Weeks 0 to 48 ]
5. Changes from baseline in cerebrospinal fluid human apolipoproteins [ Time Frame: Weeks 0 to 25 ]
6. Changes from baseline in plasma beta-methylamino-L-alanine levels [ Time Frame: Weeks 0 to 48 ]
7. Changes from baseline in cerebrospinal fluid beta-methylamino-L-alanine levels [ Time Frame: Weeks 0 to 25 ]
8. Changes from baseline in absolute leukocyte count [ Time Frame: Weeks 0 to 48 ]
9. Changes from baseline in plasma neurofilament analysis [ Time Frame: Weeks 0 to 48 ]
10. Changes from baseline in cerebrospinal fluid neurofilament analysis [ Time Frame: Weeks 0 to 25 ]

Other Outcome Measures:

1. 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 ]
2. 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 ]
3. Incidence of all AEs [ Time Frame: Weeks -2 to 48 ]

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 69 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 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 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/μL)
  2. Fibrinogen <1.5 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 mg/dL
• Presence of heart disease that contraindicates PE treatment, including ischemic cardiopathy and congestive heart failure
• Presence of prior behavioral 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.)

Contacts and Locations

Locations

United States, New Hampshire

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States, 03756

Sponsors and Collaborators

Grifols Therapeutics LLC

Grifols Biologicals, LLC

More Information

• Responsible Party: Grifols Therapeutics LLC
• ClinicalTrials.gov Identifier: NCT02872142
• Other Study ID Numbers: GBI1501
• First Posted: August 19, 2016
• Last Update Posted: March 13, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases