A Study of IPL344 in the Treatment of ALS Patients

Study Overview
=================
Brief Summary
-----------------
This is a prospective, open-label, phase 1/2a study, dose escalation, to evaluate tolerability, safety, and PK of I.V. administered IPL344 in participants with Amyotrophic Lateral Sclerosis (ALS).

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.

Official Title
-----------------
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)

Conditions
-----------------
Amyotrophic Lateral Sclerosis

Intervention / Treatment
-----------------
* Drug: IPL344


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPL344<br>IPL344 will be administered Intravenously on a daily basis. The dose range of IPL344 is 1.7-3.2 mg/kg | Drug: IPL344<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AEs) and serious adverse events (SAEs) Reporting | All AEs will be recorded, whether considered minor or serious, drug-related or not | (up-to Day 56) | 
| Maximum Tolerated Dose (MTD) | 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) | 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 - Area Under the Curve (AUC) | 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) | 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) | 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 |