Clinical trial NCT02872142: Efficacy and Safety of Plasma Exchange With Albutein® 5% in Participants With Amyotrophic Lateral Sclerosis
Official title: Pilot Study to Evaluate the Efficacy and Safety of Plasma Exchange With Albutein® 5% in Patients With Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
Collaborators: name: Grifols Biologicals, LLC
First posted: 2016-08-19
Enrollment: 12
Sex: ALL
Minimum age (years): 19
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Eligibility 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 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.)

Primary outcomes:
measure: Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score
timeFrame: Baseline (Week 0), Weeks 4, 12, 25, 36, and 48
measure: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC)
timeFrame: Baseline (Week 0), Weeks 4, 12, 25, 36, and 48
Secondary outcomes:
measure: 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
timeFrame: Baseline (Week 0), Weeks 25, and 48
measure: 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
timeFrame: Baseline (Week 0), Weeks 25, and 48
measure: Change From Baseline in Cognitive Function as Assessed by Cognitive Screening Section Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test
timeFrame: Baseline (Week 0), Weeks 25, and 48
measure: Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG)
timeFrame: Baseline (Week 0), Weeks 4, 12, 25, 36, and 48
measure: Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score
timeFrame: Weeks 25 and 48
measure: Change From Baseline in Plasma Human Apolipoprotein Levels
timeFrame: Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
measure: Change From Baseline in Plasma Cytokine Panel Levels
timeFrame: Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
measure: Change From Baseline in Cerebrospinal Fluid (CSF) Human Apolipoprotein Levels
timeFrame: Baseline (Week 0), Weeks 12, and 25
measure: Change From Baseline in CSF Cytokine Panel Levels
timeFrame: Baseline (Week 0), Weeks 12, and 25
measure: Change From Baseline in Plasma Beta-methylamino-L-alanine (BMAA) Levels
timeFrame: Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
measure: Change From Cerebrospinal Fluid (CSF) Beta-methylamino-L-alanine (BMAA) Levels
timeFrame: Baseline (Week 0), Weeks 12, and 25
measure: Change From Baseline in Absolute Leukocyte Count
timeFrame: Baseline, Weeks 4, 12, and 48
measure: Change From Baseline in Immune Population Profile
timeFrame: Baseline, Weeks 4, 12, and 48
measure: Change From Baseline in Plasma Neurofilament Levels
timeFrame: Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
measure: Change From Baseline in Cerebrospinal Fluid (CSF) Neurofilament Levels
timeFrame: Baseline (Week 0), Weeks 12, and 25
Other outcomes:
measure: Percentage of PE Sessions Associated With at Least One Adverse Reaction (AR)
timeFrame: During or within 72 hours after the completion of the product infusion
measure: Percentage of PE Sessions Associated With at Least One Adverse Event (AE), Irrespective of Causality
timeFrame: During or within 72 hours after the completion of the product infusion
measure: Incidence of All AEs
timeFrame: Weeks -2 to 48
Locations:
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
Study officials:
References: