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

NCT03613571 | Terminated Phase 2

• 2 other identifiers: 1.5, 2019-06-252017-005065-47
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (17)

• 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

• 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

• Change in vital signs - blood pressure

  Percent change in blood pressure (mmHg) from baseline at 3 months

  up to 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

  up to 3 months

• Change in vital signs - heart rate

  Percent change in heart rate (bpm, beats per minute) from baseline at 3 months

  up to 3 months

• Change in vital signs - body temperatue

  Percent change in body temperature (degrees Celsius) from baseline at 3 months

  up to 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.

  up to 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.

  up to 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.

  up to 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.

  up to 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.

  up to 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.

  up to 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.

  up to 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.

  up to 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.

  up to 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.

  up to 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.

  up to 3 months

Secondary Outcomes (9)

• Change in functional rating with Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R)

  up to 3 months

• Change in functional rating with Norris rating scale

  up to 3 months

• Change in pulmonary function (FVC) from baseline

  up to 3 months

• Change in Quality of Life (QoL) assessed by visual analogue scale (VAS)

  up to 1.5 months

• Change in functional rating of autonomous and sensory symptoms

  up to 3 months

Study Arms (1)

ILB

EXPERIMENTAL

ILB treatment

Drug: ILB

Interventions

ILB DRUG

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.

ILB

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• TikoMed AB: lead

Study Sites (1)

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Related Publications (2)

• 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.

  PMID: 35613082 RESULT

• 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.

  PMID: 34442438 RESULT

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

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

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: June 15, 2018
• First Posted: August 3, 2018
• Study Start: August 15, 2018
• Primary Completion: August 20, 2019
• Study Completion: August 20, 2019
• Last Updated: June 12, 2023

Record last verified: 2023-06

Locations

SE (1)