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A Study of IPL344 in the Treatment of ALS Patients (ALS)

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ClinicalTrials.gov Identifier: NCT03652805
Recruitment Status : Recruiting
First Posted : August 29, 2018
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Immunity Pharma Ltd.

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).

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: IPL344 Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : August 1, 2018
Estimated Primary Completion Date : July 15, 2019
Estimated Study Completion Date : August 15, 2019


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
Drug: IPL344

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.





Primary Outcome Measures :
  1. 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

  2. Maximum Tolerated Dose (MTD) [ Time Frame: Study treatment duration (Day 1 -28 days) ]
    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).


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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


Other Outcome Measures:
  1. Exploratory: Biomarker testing [ Time Frame: up-to Day 56 ]
    Blood samples for exploratory Biomarkers (Biobanking)

  2. Exploratory: Anti-Drug Antibody (ADA) testing [ Time Frame: up-to Day 56 ]
    Blood samples for Anti-Drug Antibody (Biobanking)

  3. Exploratory: identify a marker based on the mechanism of action (MOA) [ Time Frame: up-to Day 56 ]
    Blood samples for future PD (Biobanking)

  4. Changes from baseline in ALS disease progression [ Time Frame: up-to day 56 ]
    ALS functional rating scale-Revised (ALSFRS-R) - Questionnaire

  5. Changes from baseline in Pulmonary Function [ Time Frame: up-to day 56 ]
    Measured by Vital Capacity (VC)

  6. Changes from baseline in Muscle strength [ Time Frame: up-to day 56 ]
    Assessed by using a quantitative strength testing tool, Hand Held Dynamometry (HHD)

  7. Changes from baseline in Anti-Depression effect [ Time Frame: up-to day 56 ]
    Evaluated by ALS Depression Inventory (ADI-12) - questionnaire

  8. Changes from baseline in Anti-Depression effect [ Time Frame: up-to day 56 ]
    the Hospital Anxiety and Depression Scale (HADS) - questionnaire



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03652805


Contacts
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Contact: Marc Gotkine, M.D. +972 2 6778899 marc@gotkine.com

Locations
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Israel
Hadassah Medical Center -Motor Neuron Disease Clinic Recruiting
Jerusalem, Israel
Contact: Marc Gotkune, M.D.    +972 2 6778899    marc@gotkine.com   
Principal Investigator: Marc Kotkine, M.D.         
Sponsors and Collaborators
Immunity Pharma Ltd.

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Responsible Party: Immunity Pharma Ltd.
ClinicalTrials.gov Identifier: NCT03652805     History of Changes
Other Study ID Numbers: 101/ 2
First Posted: August 29, 2018    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases