A Safety and Tolerability Study of ILB® in Patients With Amyotrophic Lateral Sclerosis (ALS)

NCT03705390 | Terminated Phase 2 Results DMC

• 1 other identifier: RG_17-250
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II study to determine the safety and tolerability of ILB®, a type of low molecular weight dextran sulfate, in patients with Motor Neurone Disease (MND)/ Amyotrophic Lateral Sclerosis (ALS)

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Keywords

ILB; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; ALS

Outcome Measures

Primary Outcomes (14)

• Safety Assessed by SAEs and AEs - Measured by Incidence

  Measured by the number of serious adverse events (SAEs) and adverse events (AEs) using CTCAE grading v4.0.

  From informed consent up to 30 days after last administration of trial treatment

• Safety Assessed by AEs - Summarised by Grade

  Grade refers to the severity of the AE as follows: Grade 1 - Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 - Moderate; minimal, local or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related to AE.

  From informed consent up to 30 days after last administration of trial treatment

• Safety Assessed by AEs - Summarised by Relatedness

  Relatedness categories: 1 = unrelated, 2 = unlikely to be related, 3 = possibly related, 4 = probably related, 5 = definitely related

  From informed consent up to 30 days after last administration of trial treatment

• Safety Assessed by SAEs - Summarised by Admitting Event Grade

  Grade refers to the severity of the admitting event as follows: Grade 1 - Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 - Moderate; minimal, local or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related to AE.

  From informed consent up to 30 days after last administration of trial treatment

• Safety Assessed by SAEs - Summarised by Admitting Event Relatedness

  Relatedness categories: 1 = unrelated, 2 = unlikely to be related, 3 = possibly related, 4 = probably related, 5 = definitely related

  From informed consent up to 30 days after last administration of trial treatment

• Safety Assessed by SAEs - Summarised by Admitting Event Type

  Description of the main event type - primary cause of admission (body system, Adverse event term and grade)

  From informed consent up to 30 days after last administration of trial treatment

• Safety Assessed by SAEs - Summarised by Expectedness

  Serious Adverse Events only will be defined as expected or unexpected based on information provided in the Quick Reference Document

  From informed consent up to 30 days after last administration of trial treatment

• Safety Assessed by SAEs - Summarised by Sequelae

  Outcome of serious adverse events only: Resolved with sequelae or Resolved without sequelae

  From informed consent up to 30 days after last administration of trial treatment

• Tolerability Assessed by the Incidence of Intolerable Adverse Events

  An intolerable adverse event will satisfy all of the following criteria: 1. Associated with a serious adverse event or a drug discontinuation of greater than three weeks; 2. Grade 3, 4 or 5 in severity according to CTCAE version 4; 3. In the opinion of the Investigator is i) definitely related or ii) probably related or iii) possibly related to the study drug treatment. Adverse events which are considered unrelated or probably not related will not be classed as intolerable events.

  From informed consent up to 30 days after last administration of trial treatment

• Quantity of Study Drug Administered - Total Drug Administered

  Total drug administered over the study period (measured in milligrams)

  From baseline to final treatment visit

• Quantity of Study Drug Administered - Number of Administrations

  Numerical count of the number of study drug injections given whilst on the trial

  From baseline to final treatment visit

• Quantity of Study Drug Administered - Number of Interruptions

  Numerical count of the number of study drug injections missed whilst on the trial

  From baseline to final treatment visit

• Quantity of Study Drug Administered - Duration of Interruptions

  Length of interruptions in weeks between study drug injections for those participants that experienced a treatment interruption whilst on the trial

  From baseline to final treatment visit

• Quantity of Study Drug Administered - Number of Discontinuations

  numerical count of patients who have discontinued study drug treatment

  From baseline to final treatment visit

Secondary Outcomes (9)

• Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) Score Change

  From baseline to final treatment visit

• Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) Score Change

  From baseline to final treatment visit

• Urinary p75ECD Change

  From baseline to final treatment visit

• Pharmacokinetics (PK; Amount of Detectable Drug) of ILB® in Plasma Following Administration

  0.5,1,2,2.5,3,4 and 6 hours post first ILB® administration

• Pharmacokinetics (PK; Tmax) Statistics of ILB® in Plasma Following Administration

  0.5,1,2,2.5,3,4 and 6 hours post first ILB® administration

Study Arms (1)

ILB® Arm

EXPERIMENTAL

ILB® subcutaneous injection at a dose of 2mg/kg once per week for up to a maximum of 48 weeks

Drug: ILB®

Interventions

ILB® DRUG

Administration will be weekly subcutaneous injections at a dose of 2mg/kg once per week for up to a maximum of 48 weeks

Also known as: DSSS5, TM-500, TM-700, LMW-DS, IBsolvMIR

ILB® Arm

Eligibility Criteria

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

You may qualify if:

• Patients ≥18 years and who have provided written informed consent to participate in the study
• Prior to trial entry patients will have a definite diagnosis of ALS according to El Escorial Criteria. All patients will demonstrate either:
• presence of Upper Motor Neuron (UMN) (increased tone, brisk reflexes) as well as Lower Motor Neuron (LMN) (weakness,
• wasting and fasciculation) signs in the bulbar region and at least two of the other spinal regions (cervical, thoracic or lumbosacral) or
• presence of UMN and LMN signs in all three spinal regions (cervical, thoracic or lumbosacral)
• Electrophysiological tests (Electromyography (EMG) / Nerve Conduction Study (NCS)) that supports the diagnosis of Motor Neurone Disease (MND) and to exclude mimic disorders
• Forced Vital Capacity (FVC) ≥50% of predicted value for gender, height and age at screening and a mean Sniff Nasal Inspiratory Pressure (SNIP) ≥50% of predicted value for age
• Adequate haematological function (Hb≥10g/dl absolute neutrophil count ≥1.5x109/L and a platelet count ≥60 x109/L
• International Normalised Ratio (INR) ≤ 1.5, Activated Partial Thromboplastin Time (aPTT) 30 - 40 seconds, Prothrombin Time (PT) 11-13.5 seconds
• Patient willing and able to comply with schedule visits, treatment plan and other study procedures.
• Patients taking Riluzole must have discontinued treatment ≥28 days prior to study entry (and following consent to take part in the study)
• Women Of Child Bearing Potential (WOCBP) who agree to use highly effective means of contraception (as defined in the Heads of Medicines Agencies\_Clinical Trials Facilitation Group (HMA\_CTFG) guideline (see Appendix 8) and in combination with a barrier contraception method (condom, diaphragm or cap) for the entirety of the study

You may not qualify if:

• Patients classified as either probable or possible ALS according to El Escorial Criteria.
• Subjects in whom other causes of neuromuscular weakness have not been excluded
• Assisted ventilation of any type within 3 months before the screening visit or at screening
• Patients requiring Radiologically Inserted Gastrostomy (RIG) or Percutaneous Endoscopic Gastroscopy (PEG) feeding
• Involvement in any other interventional study involving use of another Investigational Medicinal Product (IMP) or biological product, within 3 months of screening
• Any use of antioxidants, edaravone, tirasemtiv or CK-2127107 within 1 month before the screening visit
• Any botulinum toxin use within 3 months before the screening visit.
• Any form of stem cell or gene therapy for the treatment of amyotrophic lateral sclerosis (ALS)
• Neuroimaging of brain and cervical spine with Magnetic Resonance imaging (MRI) indicating compressive myelopathy as an alternate diagnosis
• Laboratory examinations including Acetylcholine receptor (AChR) antibodies and Muscle Specific Kinase (MuSK) antibodies to exclude Bulbar onset Myasthenia gravis from Bulbar onset Motor neuron disease as an alternate diagnosis and Antinuclear Antibodies (ANA), Anti-neutrophil cytoplasmic antibodies (ANCA), Extractable Nuclear Antigen (ENA) antibodies, Creatine Kinase (CK), electrophoresis and immunoglobulin indicating an alternate diagnosis for muscle disease like Myositis
• Abnormal liver function defined as Aspartate Transaminase (AST) and/or Alanine Transaminase (ALT) \>3 times upper limit of normal
• Any head trauma, intracranial or spinal surgery within 3 months of trial entry
• Patients who have had recurrent falls will be excluded to reduce the risk of intracerebral haemorrhage with this IMP
• Current use of an anticoagulant e.g Warfarin, Aspirin, Clopidogrel, any novel anticoagulants (NOAC)s or low molecular weight subcutaneous heparin
• Uncontrolled severe hypertension defined as systolic blood pressure (SBP) ≥ 220 mmHg or diastolic blood pressure (DBP) ≥120 mmHg

Sponsors & Collaborators

• University of Birmingham: lead
• TikoMed AB: collaborator
• University Hospital Birmingham: collaborator
• Neuregenix Ltd: collaborator

Study Sites (1)

University Hospitals Birmingham NHS Foundation Trust

Birmingham, West Midlands, B15 2TH, United Kingdom

Location

Related Publications (1)

• Srinivasan V, Homer V, Barton D, Clutterbuck-James A, Jenkins S, Potter C, Brock K, Logan A, Smith D, Bruce L, Nagy Z, Bach SP. A low molecular weight dextran sulphate, ILB(R), for the treatment of amyotrophic lateral sclerosis (ALS): An open-label, single-arm, single-centre, phase II trial. PLoS One. 2024 Jul 11;19(7):e0291285. doi: 10.1371/journal.pone.0291285. eCollection 2024.

  PMID: 38990927 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

Early termination due to the COVID-19 pandemic, the high-risk status of trial patients, and the frequent hospital based visits, meant that both recruitment to the trial and further treatment was suspended after 11 patients had been recruited. As a result, patients were treated with interrupted and varying numbers of weekly ILB® treatments. The pharmacokinetic evaluation was limited due to rejection of some poor quality blood samples.

Results Point of Contact

• Title: D3B Trial Mangement Team Leader
• Organization: CRCTU, University of Birmingham

ALS@trials.bham.ac.uk

+44 (0) 121 371 8027

Study Officials

• Venkataramanan Srinivasan, MRCP, MRCP

  University of Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2018
• First Posted: October 15, 2018
• Study Start: March 29, 2019
• Primary Completion: July 28, 2021
• Study Completion: July 28, 2021
• Last Updated: June 26, 2025
• Results First Posted: June 26, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)