A Study to Evaluate the Safety, Tolerability and Efficacy of ILB in Patients With Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03613571
• Other study ID #: 1.5, 2019-06-25
• Secondary ID: 2017-005065-47
• Status: Terminated
• Phase: Phase 2
• Start date: August 15, 2018
• Est. completion date: August 20, 2019

Study information

• Verified date: June 2023
• Source: TikoMed AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: August 20, 2019
• Est. primary completion date: August 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Willing and able to give written informed consent for participation in the study.

2. Clinical diagnosis of Amyotrophic Lateral Sclerosis (ALS).

3. Male or female patients between 18 to 80 years (inclusive).

4. Forced Vital Capacity (FVC) 65% of predicted value for gender, height and age at screening.

5. Evaluated with ALSFRS-R and Norris clinical rating scales for at least the past 4 weeks before study drug administration.

Exclusion criteria

1. Unable to understand information about the study or are expected not to collaborate with the study team.

2. Concurrent serious disease, other than ALS, at the discretion of the nvestigator.

3. Pregnancy.

4. 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.

5. Addiction to drugs or alcohol.

6. Confirmed HIV, hepatitis B or hepatitis C.

7. Known bleeding disorders or abnormal bleeding events.

8. Treatment with anticoagulant drugs warfarin and novel oral anticoagulants (NOAC) within the last 14 days prior to screening.

9. Treatment with Riluzole or Lamotrigine within the last 28 days prior to study drug administration.

10. Hypersensitivity to dextran sulfate.

11. Poor venous access.

12. Patients with clinically significant abnormal PK-INR, fibrinogen, von Willebrand factor and activated partial thromboplastin time (APTT) at screening.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• ILB
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.

Locations

Country	Name	City	State
Sweden	Sahlgrenska University Hospital	Gothenburg

Sponsors (1)

Lead Sponsor	Collaborator
TikoMed AB

Country where clinical trial is conducted

Sweden, 

References & Publications (2)

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 M — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	up to 3 months
Primary	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.	up to 3 months
Primary	Change in vital signs - blood pressure	Percent change in blood pressure (mmHg) from baseline at 3 months	up to 3 months
Primary	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	up to 3 months
Primary	Change in vital signs - heart rate	Percent change in heart rate (bpm, beats per minute) from baseline at 3 months	up to 3 months
Primary	Change in vital signs - body temperatue	Percent change in body temperature (degrees Celsius) from baseline at 3 months	up to 3 months
Primary	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.	up to 3 months
Primary	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.	up to 3 months
Primary	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.	up to 3 months
Primary	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.	up to 3 months
Primary	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.	up to 3 months
Primary	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.	up to 3 months
Primary	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.	up to 3 months
Primary	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.	up to 3 months
Primary	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.	up to 3 months
Primary	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.	up to 3 months
Primary	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.	up to 3 months
Secondary	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	up to 3 months
Secondary	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	up to 3 months
Secondary	Change in pulmonary function (FVC) from baseline		up to 3 months
Secondary	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	up to 1.5 months
Secondary	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	up to 3 months
Secondary	Change in maximum plasma concentration (Cmax) of ILB		up to 1 month
Secondary	Change in exposure (Area Under the Curve, AUC) of ILB		up to 1 month
Secondary	Changes in APTT (effect APTT) from day of dosing (day 1)		up to 1 month
Secondary	Change in plasma concentration of hepatocyte growth factor (HGF)		up to 1 month