- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03652805
A Study of IPL344 in the Treatment of ALS Patients (ALS)
Phase 1/2a, Multi-center, Open-Label, Dose-escalating Study to Assess Safety, Tolerability, and Pharmacokinetics of Intravenously Administered IPL344 for The Treatment of Amyotrophic Lateral Sclerosis (ALS)
Study Overview
Detailed Description
The study is designed to determine the tolerability, safety and PK of IPL344 administered I.V. once a day for 28 days and to identify the maximum tolerated dose.
All patients enrolled will have a documented history of ALS disease prior to study enrollment.
Treatment will start with 1.7mg/kg with dose escalation by 0.5 mg/kg every 3-4 days and will increase to the maximum dose of 3.2mg/kg. Day 1 to Day 28 patients will be on active treatment.
After completion of 28 treatment days, participants who will choose to continue treatment (at the investigator's discretion), will be enrolled in a follow-up study. Participants that discontinue treatment after Day 28 will be followed up by a nurse phone call and return to the clinic for a final visit on Day 56 from the first dose.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Marc Gotkine, M.D.
- Phone Number: +972 2 6778899
- Email: marc@gotkine.com
Study Locations
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-
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Jerusalem, Israel
- Hadassah Medical Center -Motor Neuron Disease Clinic
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male or female participants ages ≥18 to 80 years
- Consenting participants fulfilling the El Escorial criteria for probable and definite ALS (sporadic and familial)
Participant has ALSFRS-R score >20, the latest ALSFRS-R test should be no more than 6 weeks before screening visit, AND:
- a disease progression rate greater than 0.55 ALSFRS-R point per month on average, over at least 4 months, prior to the latest ALSFRS-R test OR
- a decline of at least 3 points in ALSFRS-R score within the last 4 months prior to the latest ALSFRS-R test
- Previous data of Force Vital Capacity (FVC) of ≥60% at least 3 months before screening and not more than 12 months.
- Written informed consent consistent with ICH-GCP and local laws, signed prior to any study procedures being performed.
- BMI 18.5 to 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg.
- If taking riluzole or edaravone, the participant must be on a stable dose for ≥30 days prior to Day 1 and expected to remain at that dose until the final study visit.
- Medically able to undergo the study procedures, and to adhere to the visit schedule at the time of study entry.
- Medically is able and willing to undergo placement and maintain a central venous catheter as determined by the investigator.
- Participant has a competent caregiver or qualified individual who can and will be responsible for the administration of study drug and reporting home activities.
- Geographic accessibility to the study site
- Females must not be lactating or pregnant at Screening, as documented by a negative beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG].
- Women of child-bearing potential or males whose partners are women of child-bearing potential use an effective method of contraception throughout the trial.
Exclusion Criteria:
- Concurrent therapy that, in the PI's opinion, would interfere with the evaluation of the safety or efficacy of the study medication.
- Co-existing psychiatric disorder excluding a depression disorder occurred after ALS diagnosis.
- Participant is a respiratory dependent.
- Subjects with a significant pulmonary disorder not attributed to ALS.
- Slow Vital Capacity (SVC) <60.
- Presence of any other condition or circumstance that, in the judgment of the Investigator, might contraindicate or increase the risk to the participant or decrease the chance of obtaining satisfactory data to achieve the objectives of the study.
- History of HIV, positive HBV or HCV serology.
- Participants suffering from significant cardiac, or any other disease that may endanger the participant or interfere with the ability to interpret the results.
- A participant with active infections.
- Documented active cancer.
- Treatment with another investigational drug, biological agent, or device within 2 months of the first dose, or investigational cell therapy within 6 months of the first dose.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: IPL344
IPL344 will be administered Intravenously on a daily basis.
The dose range of IPL344 is 1.7-3.2
mg/kg
|
The study is designed to determine the tolerability, safety and PK of IPL344 administered I.V. once a day for 28 days and to identify the maximum tolerated dose. All patients enrolled will have a documented history of ALS disease prior to study enrollment. Treatment will start with 1.7mg/kg with dose escalation by 0.5 mg/kg every 3-4 days and will increase to the maximum dose of 3.2mg/kg. Day 1 to Day 28 patients will be on active treatment. After completion of 28 treatment days, participants who will choose to continue treatment (at the investigator's discretion), will be enrolled in a follow-up study. Participants that discontinue treatment after Day 28 will be followed up by a nurse phone call and return to the clinic for a final visit on Day 56 from the first dose. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse Events (AEs) and serious adverse events (SAEs) Reporting
Time Frame: (up-to Day 56)
|
All AEs will be recorded, whether considered minor or serious, drug-related or not
|
(up-to Day 56)
|
Maximum Tolerated Dose (MTD)
Time Frame: Study treatment duration (Day 1 -28 days)
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Dose defined as the highest dose with no Dose Limiting Toxicity (DLT).
DLT will be defined as a Grade ≥ 3 toxicity per participant according to Common Terminology Criteria for Adverse Events (CTCAE v5.0).
|
Study treatment duration (Day 1 -28 days)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetic (PK) profile - Maximum Plasma Concentration (Cmax)
Time Frame: Pre-Dose and 5, 10, 20, 30, 45, 60 and 120 minutes after dosing
|
Blood will be collected for PK testing on Day 1 prior to and after first dose and on each dose-escalation administration day and on Day 28
|
Pre-Dose and 5, 10, 20, 30, 45, 60 and 120 minutes after dosing
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Pharmacokinetic (PK) profile - Area Under the Curve (AUC)
Time Frame: Pre-Dose and 5, 10, 20, 30, 45, 60 and 120 minutes after dosing
|
Blood will be collected for PK testing on Day 1 prior to and after first dose and on each dose-escalation administration day and on Day 28
|
Pre-Dose and 5, 10, 20, 30, 45, 60 and 120 minutes after dosing
|
Pharmacokinetic (PK) profile - time to reach maximum plasma concentration (Tmax)
Time Frame: Pre-Dose and 5, 10, 20, 30, 45, 60 and 120 minutes after dosing
|
Blood will be collected for PK testing on Day 1 prior to and after first dose and on each dose-escalation administration day and on Day 28
|
Pre-Dose and 5, 10, 20, 30, 45, 60 and 120 minutes after dosing
|
Pharmacokinetic (PK) profile - apparent terminal exponential half-life (T1/2)
Time Frame: Pre-Dose and 5, 10, 20, 30, 45, 60 and 120 minutes after dosing
|
Blood will be collected for PK testing on Day 1 prior to and after first dose and on each dose-escalation administration day and on Day 28
|
Pre-Dose and 5, 10, 20, 30, 45, 60 and 120 minutes after dosing
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exploratory: Biomarker testing
Time Frame: up-to Day 56
|
Blood samples for exploratory Biomarkers (Biobanking)
|
up-to Day 56
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Exploratory: Anti-Drug Antibody (ADA) testing
Time Frame: up-to Day 56
|
Blood samples for Anti-Drug Antibody (Biobanking)
|
up-to Day 56
|
Exploratory: identify a marker based on the mechanism of action (MOA)
Time Frame: up-to Day 56
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Blood samples for future PD (Biobanking)
|
up-to Day 56
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Changes from baseline in ALS disease progression
Time Frame: up-to day 56
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ALS functional rating scale-Revised (ALSFRS-R) - Questionnaire
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up-to day 56
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Changes from baseline in Pulmonary Function
Time Frame: up-to day 56
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Measured by Vital Capacity (VC)
|
up-to day 56
|
Changes from baseline in Muscle strength
Time Frame: up-to day 56
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Assessed by using a quantitative strength testing tool, Hand Held Dynamometry (HHD)
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up-to day 56
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Changes from baseline in Anti-Depression effect
Time Frame: up-to day 56
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Evaluated by ALS Depression Inventory (ADI-12) - questionnaire
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up-to day 56
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Changes from baseline in Anti-Depression effect
Time Frame: up-to day 56
|
the Hospital Anxiety and Depression Scale (HADS) - questionnaire
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up-to day 56
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 101/ 2
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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