Clinical trial NCT03652805: A Study of IPL344 in the Treatment of ALS Patients
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)
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: Immunity Pharma Ltd.
Sponsor class: INDUSTRY
First posted: 2018-08-29
Enrollment: 15
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 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female participants ages ≥18 to 80 years
2. Consenting participants fulfilling the El Escorial criteria for probable and definite ALS (sporadic and familial)
3. Participant has ALSFRS-R score \>20, the latest ALSFRS-R test should be no more than 6 weeks before screening visit, AND:

   1. 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
   2. a decline of at least 3 points in ALSFRS-R score within the last 4 months prior to the latest ALSFRS-R test
4. Previous data of Force Vital Capacity (FVC) of ≥60% at least 3 months before screening and not more than 12 months.
5. Written informed consent consistent with ICH-GCP and local laws, signed prior to any study procedures being performed.
6. BMI 18.5 to 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg.
7. 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.
8. Medically able to undergo the study procedures, and to adhere to the visit schedule at the time of study entry.
9. Medically is able and willing to undergo placement and maintain a central venous catheter as determined by the investigator.
10. Participant has a competent caregiver or qualified individual who can and will be responsible for the administration of study drug and reporting home activities.
11. Geographic accessibility to the study site
12. Females must not be lactating or pregnant at Screening, as documented by a negative beta-human chorionic gonadotropin \[ß-hCG\] (or human chorionic gonadotropin \[hCG\].
13. 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:

1. Concurrent therapy that, in the PI's opinion, would interfere with the evaluation of the safety or efficacy of the study medication.
2. Co-existing psychiatric disorder excluding a depression disorder occurred after ALS diagnosis.
3. Participant is a respiratory dependent.
4. Subjects with a significant pulmonary disorder not attributed to ALS.
5. Slow Vital Capacity (SVC) \<60.
6. 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.
7. History of HIV, positive HBV or HCV serology.
8. Participants suffering from significant cardiac, or any other disease that may endanger the participant or interfere with the ability to interpret the results.
9. A participant with active infections.
10. Documented active cancer.
11. 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.

Primary outcomes:
measure: Adverse Events (AEs) and serious adverse events (SAEs) Reporting
timeFrame: (up-to Day 56)
measure: Maximum Tolerated Dose (MTD)
timeFrame: Study treatment duration (Day 1 -28 days)
Secondary outcomes:
measure: Pharmacokinetic (PK) profile - Maximum Plasma Concentration (Cmax)
timeFrame: Pre-Dose and 5, 10, 20, 30, 45, 60 and 120 minutes after dosing
measure: Pharmacokinetic (PK) profile - Area Under the Curve (AUC)
timeFrame: Pre-Dose and 5, 10, 20, 30, 45, 60 and 120 minutes after dosing
measure: Pharmacokinetic (PK) profile - time to reach maximum plasma concentration (Tmax)
timeFrame: Pre-Dose and 5, 10, 20, 30, 45, 60 and 120 minutes after dosing
measure: Pharmacokinetic (PK) profile - apparent terminal exponential half-life (T1/2)
timeFrame: Pre-Dose and 5, 10, 20, 30, 45, 60 and 120 minutes after dosing
Other outcomes:
measure: Exploratory: Biomarker testing
timeFrame: up-to Day 56
measure: Exploratory: Anti-Drug Antibody (ADA) testing
timeFrame: up-to Day 56
measure: Exploratory: identify a marker based on the mechanism of action (MOA)
timeFrame: up-to Day 56
measure: Changes from baseline in ALS disease progression
timeFrame: up-to day 56
measure: Changes from baseline in Pulmonary Function
timeFrame: up-to day 56
measure: Changes from baseline in Muscle strength
timeFrame: up-to day 56
measure: Changes from baseline in Anti-Depression effect
timeFrame: up-to day 56
measure: Changes from baseline in Anti-Depression effect
timeFrame: up-to day 56
Locations:
city: Jerusalem
country: Israel
facility: Hadassah Medical Center -Motor Neuron Disease Clinic
Study officials:
References: