Back to resultsA Study to Evaluate the Safety, Tolerability and Efficacy of ILB in Patients With Amyotrophic Lateral Sclerosis
Primary Purpose
Amyotrophic Lateral Sclerosis
Status
Terminated
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
ILB
Sponsored by
About this trial
This is an interventional treatment trial for Amyotrophic Lateral Sclerosis
Eligibility Criteria
Inclusion Criteria:
- Willing and able to give written informed consent for participation in the study.
- Clinical diagnosis of Amyotrophic Lateral Sclerosis (ALS).
- Male or female patients between 18 to 80 years (inclusive).
- Forced Vital Capacity (FVC) 65% of predicted value for gender, height and age at screening.
- Evaluated with ALSFRS-R and Norris clinical rating scales for at least the past 4 weeks before study drug administration.
Exclusion criteria
- Unable to understand information about the study or are expected not to collaborate with the study team.
- Concurrent serious disease, other than ALS, at the discretion of the nvestigator.
- Pregnancy.
- Patients of childbearing potential not willing to use adequate double contraception with less than 1 percentage failure rate after the screening visit until the last visit.
- Addiction to drugs or alcohol.
- Confirmed HIV, hepatitis B or hepatitis C.
- Known bleeding disorders or abnormal bleeding events.
- Treatment with anticoagulant drugs warfarin and novel oral anticoagulants (NOAC) within the last 14 days prior to screening.
- Treatment with Riluzole or Lamotrigine within the last 28 days prior to study drug administration.
- Hypersensitivity to dextran sulfate.
- Poor venous access.
- Patients with clinically significant abnormal PK-INR, fibrinogen, von Willebrand factor and activated partial thromboplastin time (APTT) at screening.
Sites / Locations
- Sahlgrenska University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ILB
Arm Description
ILB treatment
Outcomes
Primary Outcome Measures
Frequency, seriousness and intensity of Treatment-emergent Adverse Events (TEAEs)
A TEAE is any adverse event (AE) not present prior to the initiation of IMP administration or any event already present that worsens in either intensity or frequency following exposure to the IMP. AEs (including baseline events) identified using any of the following methods will be recorded:
AEs spontaneously reported by the subject
AEs observed by the Investigator or medical personnel
AEs elicited based on non-leading questions from the Investigator or medical personnel
Change in physical status
A complete physical examination according to clinical praxis will be performed, including assessment of the head, eyes, ears, nose, throat (EENT), cardiac, peripheral vascular, pulmonary, musculoskeletal, neurologic, abdominal, lymphatic and dermatological functions.
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Change in vital signs - blood pressure
Percent change in blood pressure (mmHg) from baseline at 3 months
Change in electrocardiogram (ECG) recordings
Change in single 12-lead ECG (PQ/PR (ms), QRS (ms), QT (ms) and QTcF (ms)) from baseline at 3 months
Change in vital signs - heart rate
Percent change in heart rate (bpm, beats per minute) from baseline at 3 months
Change in vital signs - body temperatue
Percent change in body temperature (degrees Celsius) from baseline at 3 months
Change in safety laboratory measurements - sodium, potassium, chloride, calcium, glucose (non-fasting)
According to clinical praxis, laboratory tests for sodium, potassium, chloride, calcium, glucose (non-fasting) will be analysed. Unit of measure is mmol/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Change in safety laboratory measurements - albumin
According to clinical praxis, laboratory test for albumin will be analysed. Unit of measure is g/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Change in safety laboratory measurements - AST, ALT, CK, alkaline phosphatase
According to clinical praxis, laboratory tests for aspartate amino-transferase (AST), alanine amino-transferase (ALT), creatine kinase (CK) and alkaline phosphatase will be analysed. Unit of measure is micro-kat/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Change in safety laboratory measurements - creatinine and total bilirubin
According to clinical praxis, laboratory tests for creatinine and total bilirubin will be analysed. Unit of measure is micro-mol/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Change in safety laboratory measurements - myoglobin
According to clinical praxis, laboratory test for myoglobin will be analysed. Unit of measure is micro-g/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Change in safety laboratory measurements - CRP
According to clinical praxis, laboratory test for C-reactive protein (CRP) will be analysed. Unit of measure is milli-g/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Change in hematology laboratory measurements - Hemoglobin and fibrinogen
According to clinical praxis, laboratory tests for hemoglobin (Hb) and fibrinogen will be analysed. Unit of measure is g/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Change in hematology laboratory measurements - Red blood cell count
According to clinical praxis, laboratory test for blood cell count (RBC) will be analysed. Unit of measure is 10x12/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Change in hematology laboratory measurements - WBC, platelets, basophils, eosinophils, lymphocytes, monocytes, neutrophils
According to clinical praxis, laboratory tests for white blood cell count (WBC), platelets, basophils, eosinophils, lymphocytes, monocytes and neutrophils will be analysed. Unit of measure is 10x9/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Change in hematology laboratory measurements - APTT
According to clinical praxis, laboratory test for activated partial thromboplastin time (aPTT) will be analysed. Unit of measure is s
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Change in hematology laboratory measurements - PK-INR
According to clinical praxis, laboratory test for prothrombin kinase international normalized ratio (PK-INR) will be analysed. Unitless measure
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Secondary Outcome Measures
Change in functional rating with Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R)
The ALSFRS-R provides a physician-generated estimate of the patient's degree of functional impairment, which can be evaluated serially to objectively assess any response to treatment or progression of disease. The ALSFRS-R includes questions that ask the physician to rate his/her impression of the patients level of functional impairment in performing one of twelve common tasks. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 48=best
Absolute change from baseline at 3 months
Change in functional rating with Norris rating scale
The Norris rating scale provides a physician-generated estimate of the patient's degree of functional impairment, which can be evaluated serially to objectively assess any response to treatment or progression of disease. The Norris rating scale includes questions that ask the physician to rate his/her impression of the patients level of functional impairment in performing one of 34 common tasks and bodily functions. Each task or function is rated on a four-point scale from 0 = can't do, to 3 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 100=best
Absolute change from baseline at 3 months
Change in pulmonary function (FVC) from baseline
Change in Quality of Life (QoL) assessed by visual analogue scale (VAS)
Questionnaire with three questions for patient and next-of-kin self reporting of:
general health status
physical health status
mental health status
Each item is rated on a millimeter scale from 0 = very bad, to 100 = very good
Absolute change from baseline at 3 months
Change in functional rating of autonomous and sensory symptoms
The autonomous and sensory rating scale provides a physician-generated estimate of the patient's degree of functional impairment, which can be evaluated serially to objectively assess any response to treatment or progression of disease. The rating scale includes questions that ask the physician to rate his/her impression of the patients level of impairment in 16 autonomous and sensory functions. Each function is rated on a four-point scale from 0 = not impaired, to 3 = very impaired.
Absolute change from baseline at 3 months
Change in maximum plasma concentration (Cmax) of ILB
Change in exposure (Area Under the Curve, AUC) of ILB
Changes in APTT (effect APTT) from day of dosing (day 1)
Change in plasma concentration of hepatocyte growth factor (HGF)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03613571
Brief Title
A Study to Evaluate the Safety, Tolerability and Efficacy of ILB in Patients With Amyotrophic Lateral Sclerosis
Official Title
A Single-centre, Open Single-arm Study Where the Safety, Tolerability and Efficacy of Subcutaneously Administered ILB Will be Evaluated in Patients With Amyotrophic Lateral Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Inclusion was stopped with 13 of 15 patients recruited according to protocol. Patients responded with no safety signals. Study stop was due to slow recruitment.
Study Start Date
August 15, 2018 (Actual)
Primary Completion Date
August 20, 2019 (Actual)
Study Completion Date
August 20, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
TikoMed AB
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This is a Phase 2a single-centre, open single-arm study in patients with Amyotrophic Lateral Sclerosis (ALS) of intermediate progression rate. Eligible subjects will be administered weekly doses of ILB. A total of 5 subcutaneous (s.c.) doses will be administered at the study clinic.
The study consists of 10 visits; One 2-part screening visit, 5 ILB administration visits, and 3 follow-up visits. Each individual patient's study participation will be 4 months, including the screening and follow-up visits. Fifteen patients are planned to be included.
The primary objective of the study is to evaluate the safety and tolerability of ILB in patients diagnosed with ALS.
ILB is a solution for subcutaneous (s.c.) injection in saline solution. The dose administered will depend on the subject's body weight at the second study visit, prior to the first ILB administration.
No formal sample size calculation has been performed for this study. The proposed sample size is considered sufficient in this early phase 2 development to provide adequate information on the patients. Categorical data will be presented as counts and percentages. Continuous data will be summarised using descriptive statistics.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ILB
Arm Type
Experimental
Arm Description
ILB treatment
Intervention Type
Drug
Intervention Name(s)
ILB
Intervention Description
The investigational medicinal product ILB will be given as single short-term s.c. injections in the abdomen, the thigh or the buttock, in that order of priority. Subjects will be observed for at least 3 hours after injection.The IMP is a sterile, colourless to pale yellow solution for subcutaneous injection.
Primary Outcome Measure Information:
Title
Frequency, seriousness and intensity of Treatment-emergent Adverse Events (TEAEs)
Description
A TEAE is any adverse event (AE) not present prior to the initiation of IMP administration or any event already present that worsens in either intensity or frequency following exposure to the IMP. AEs (including baseline events) identified using any of the following methods will be recorded:
AEs spontaneously reported by the subject
AEs observed by the Investigator or medical personnel
AEs elicited based on non-leading questions from the Investigator or medical personnel
Time Frame
up to 3 months
Title
Change in physical status
Description
A complete physical examination according to clinical praxis will be performed, including assessment of the head, eyes, ears, nose, throat (EENT), cardiac, peripheral vascular, pulmonary, musculoskeletal, neurologic, abdominal, lymphatic and dermatological functions.
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Time Frame
up to 3 months
Title
Change in vital signs - blood pressure
Description
Percent change in blood pressure (mmHg) from baseline at 3 months
Time Frame
up to 3 months
Title
Change in electrocardiogram (ECG) recordings
Description
Change in single 12-lead ECG (PQ/PR (ms), QRS (ms), QT (ms) and QTcF (ms)) from baseline at 3 months
Time Frame
up to 3 months
Title
Change in vital signs - heart rate
Description
Percent change in heart rate (bpm, beats per minute) from baseline at 3 months
Time Frame
up to 3 months
Title
Change in vital signs - body temperatue
Description
Percent change in body temperature (degrees Celsius) from baseline at 3 months
Time Frame
up to 3 months
Title
Change in safety laboratory measurements - sodium, potassium, chloride, calcium, glucose (non-fasting)
Description
According to clinical praxis, laboratory tests for sodium, potassium, chloride, calcium, glucose (non-fasting) will be analysed. Unit of measure is mmol/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Time Frame
up to 3 months
Title
Change in safety laboratory measurements - albumin
Description
According to clinical praxis, laboratory test for albumin will be analysed. Unit of measure is g/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Time Frame
up to 3 months
Title
Change in safety laboratory measurements - AST, ALT, CK, alkaline phosphatase
Description
According to clinical praxis, laboratory tests for aspartate amino-transferase (AST), alanine amino-transferase (ALT), creatine kinase (CK) and alkaline phosphatase will be analysed. Unit of measure is micro-kat/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Time Frame
up to 3 months
Title
Change in safety laboratory measurements - creatinine and total bilirubin
Description
According to clinical praxis, laboratory tests for creatinine and total bilirubin will be analysed. Unit of measure is micro-mol/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Time Frame
up to 3 months
Title
Change in safety laboratory measurements - myoglobin
Description
According to clinical praxis, laboratory test for myoglobin will be analysed. Unit of measure is micro-g/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Time Frame
up to 3 months
Title
Change in safety laboratory measurements - CRP
Description
According to clinical praxis, laboratory test for C-reactive protein (CRP) will be analysed. Unit of measure is milli-g/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Time Frame
up to 3 months
Title
Change in hematology laboratory measurements - Hemoglobin and fibrinogen
Description
According to clinical praxis, laboratory tests for hemoglobin (Hb) and fibrinogen will be analysed. Unit of measure is g/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Time Frame
up to 3 months
Title
Change in hematology laboratory measurements - Red blood cell count
Description
According to clinical praxis, laboratory test for blood cell count (RBC) will be analysed. Unit of measure is 10x12/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Time Frame
up to 3 months
Title
Change in hematology laboratory measurements - WBC, platelets, basophils, eosinophils, lymphocytes, monocytes, neutrophils
Description
According to clinical praxis, laboratory tests for white blood cell count (WBC), platelets, basophils, eosinophils, lymphocytes, monocytes and neutrophils will be analysed. Unit of measure is 10x9/L
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Time Frame
up to 3 months
Title
Change in hematology laboratory measurements - APTT
Description
According to clinical praxis, laboratory test for activated partial thromboplastin time (aPTT) will be analysed. Unit of measure is s
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Time Frame
up to 3 months
Title
Change in hematology laboratory measurements - PK-INR
Description
According to clinical praxis, laboratory test for prothrombin kinase international normalized ratio (PK-INR) will be analysed. Unitless measure
According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS)
Change from baseline at 3 months.
Time Frame
up to 3 months
Secondary Outcome Measure Information:
Title
Change in functional rating with Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R)
Description
The ALSFRS-R provides a physician-generated estimate of the patient's degree of functional impairment, which can be evaluated serially to objectively assess any response to treatment or progression of disease. The ALSFRS-R includes questions that ask the physician to rate his/her impression of the patients level of functional impairment in performing one of twelve common tasks. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 48=best
Absolute change from baseline at 3 months
Time Frame
up to 3 months
Title
Change in functional rating with Norris rating scale
Description
The Norris rating scale provides a physician-generated estimate of the patient's degree of functional impairment, which can be evaluated serially to objectively assess any response to treatment or progression of disease. The Norris rating scale includes questions that ask the physician to rate his/her impression of the patients level of functional impairment in performing one of 34 common tasks and bodily functions. Each task or function is rated on a four-point scale from 0 = can't do, to 3 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 100=best
Absolute change from baseline at 3 months
Time Frame
up to 3 months
Title
Change in pulmonary function (FVC) from baseline
Time Frame
up to 3 months
Title
Change in Quality of Life (QoL) assessed by visual analogue scale (VAS)
Description
Questionnaire with three questions for patient and next-of-kin self reporting of:
general health status
physical health status
mental health status
Each item is rated on a millimeter scale from 0 = very bad, to 100 = very good
Absolute change from baseline at 3 months
Time Frame
up to 1.5 months
Title
Change in functional rating of autonomous and sensory symptoms
Description
The autonomous and sensory rating scale provides a physician-generated estimate of the patient's degree of functional impairment, which can be evaluated serially to objectively assess any response to treatment or progression of disease. The rating scale includes questions that ask the physician to rate his/her impression of the patients level of impairment in 16 autonomous and sensory functions. Each function is rated on a four-point scale from 0 = not impaired, to 3 = very impaired.
Absolute change from baseline at 3 months
Time Frame
up to 3 months
Title
Change in maximum plasma concentration (Cmax) of ILB
Time Frame
up to 1 month
Title
Change in exposure (Area Under the Curve, AUC) of ILB
Time Frame
up to 1 month
Title
Changes in APTT (effect APTT) from day of dosing (day 1)
Time Frame
up to 1 month
Title
Change in plasma concentration of hepatocyte growth factor (HGF)
Time Frame
up to 1 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Willing and able to give written informed consent for participation in the study.
Clinical diagnosis of Amyotrophic Lateral Sclerosis (ALS).
Male or female patients between 18 to 80 years (inclusive).
Forced Vital Capacity (FVC) 65% of predicted value for gender, height and age at screening.
Evaluated with ALSFRS-R and Norris clinical rating scales for at least the past 4 weeks before study drug administration.
Exclusion criteria
Unable to understand information about the study or are expected not to collaborate with the study team.
Concurrent serious disease, other than ALS, at the discretion of the nvestigator.
Pregnancy.
Patients of childbearing potential not willing to use adequate double contraception with less than 1 percentage failure rate after the screening visit until the last visit.
Addiction to drugs or alcohol.
Confirmed HIV, hepatitis B or hepatitis C.
Known bleeding disorders or abnormal bleeding events.
Treatment with anticoagulant drugs warfarin and novel oral anticoagulants (NOAC) within the last 14 days prior to screening.
Treatment with Riluzole or Lamotrigine within the last 28 days prior to study drug administration.
Hypersensitivity to dextran sulfate.
Poor venous access.
Patients with clinically significant abnormal PK-INR, fibrinogen, von Willebrand factor and activated partial thromboplastin time (APTT) at screening.
Facility Information:
Facility Name
Sahlgrenska University Hospital
City
Gothenburg
Country
Sweden
12. IPD Sharing Statement
Citations:
PubMed Identifier
35613082
Citation
Logan A, Nagy Z, Barnes NM, Belli A, Di Pietro V, Tavazzi B, Lazzarino G, Lazzarino G, Bruce L, Persson LI. A phase II open label clinical study of the safety, tolerability and efficacy of ILB(R) for Amyotrophic Lateral Sclerosis. PLoS One. 2022 May 25;17(5):e0267183. doi: 10.1371/journal.pone.0267183. eCollection 2022.
Results Reference
result
PubMed Identifier
34442438
Citation
Lazzarino G, Mangione R, Belli A, Di Pietro V, Nagy Z, Barnes NM, Bruce L, Ropero BM, Persson LI, Manca B, Saab MW, Amorini AM, Tavazzi B, Lazzarino G, Logan A. ILB(R) Attenuates Clinical Symptoms and Serum Biomarkers of Oxidative/Nitrosative Stress and Mitochondrial Dysfunction in Patients with Amyotrophic Lateral Sclerosis. J Pers Med. 2021 Aug 14;11(8):794. doi: 10.3390/jpm11080794.
Results Reference
result
Learn more about this trial
A Study to Evaluate the Safety, Tolerability and Efficacy of ILB in Patients With Amyotrophic Lateral Sclerosis
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