Clinical trial NCT03613571: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: TikoMed AB
Sponsor class: INDUSTRY
First posted: 2018-08-03
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Frequency, seriousness and intensity of Treatment-emergent Adverse Events (TEAEs)
timeFrame: up to 3 months
measure: Change in physical status
timeFrame: up to 3 months
measure: Change in vital signs - blood pressure
timeFrame: up to 3 months
measure: Change in electrocardiogram (ECG) recordings
timeFrame: up to 3 months
measure: Change in vital signs - heart rate
timeFrame: up to 3 months
measure: Change in vital signs - body temperatue
timeFrame: up to 3 months
measure: Change in safety laboratory measurements - sodium, potassium, chloride, calcium, glucose (non-fasting)
timeFrame: up to 3 months
measure: Change in safety laboratory measurements - albumin
timeFrame: up to 3 months
measure: Change in safety laboratory measurements - AST, ALT, CK, alkaline phosphatase
timeFrame: up to 3 months
measure: Change in safety laboratory measurements - creatinine and total bilirubin
timeFrame: up to 3 months
measure: Change in safety laboratory measurements - myoglobin
timeFrame: up to 3 months
measure: Change in safety laboratory measurements - CRP
timeFrame: up to 3 months
measure: Change in hematology laboratory measurements - Hemoglobin and fibrinogen
timeFrame: up to 3 months
measure: Change in hematology laboratory measurements - Red blood cell count
timeFrame: up to 3 months
measure: Change in hematology laboratory measurements - WBC, platelets, basophils, eosinophils, lymphocytes, monocytes, neutrophils
timeFrame: up to 3 months
measure: Change in hematology laboratory measurements - APTT
timeFrame: up to 3 months
measure: Change in hematology laboratory measurements - PK-INR
timeFrame: up to 3 months
Secondary outcomes:
measure: Change in functional rating with Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R)
timeFrame: up to 3 months
measure: Change in functional rating with Norris rating scale
timeFrame: up to 3 months
measure: Change in pulmonary function (FVC) from baseline
timeFrame: up to 3 months
measure: Change in Quality of Life (QoL) assessed by visual analogue scale (VAS)
timeFrame: up to 1.5 months
measure: Change in functional rating of autonomous and sensory symptoms
timeFrame: up to 3 months
measure: Change in maximum plasma concentration (Cmax) of ILB
timeFrame: up to 1 month
measure: Change in exposure (Area Under the Curve, AUC) of ILB
timeFrame: up to 1 month
measure: Changes in APTT (effect APTT) from day of dosing (day 1)
timeFrame: up to 1 month
measure: Change in plasma concentration of hepatocyte growth factor (HGF)
timeFrame: up to 1 month
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
Study officials:
References:
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.
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.