None listed
Conditions
Brief summary
This study is a FIH, open label, SAD and MAD study to determine the safety and PK characteristics of mEphA4-Fc in HVs and patients with ALS. Measurements of clinical endpoints associated with ALS will also be assessed. All potential subjects will be required to provide written informed consent prior to any study specific Screening procedures being performed. Subjects eligible to participate in the study will be assigned to receive their first IMP administration no later than 28 days after Screening. Part 1 (SAD): Total of 20 healthy volunteers (HVs) in five cohorts Part 2 (MAD): Total of 8 ALS patients in two cohorts Part 3 (Extended Access Study): Total of 8 ALS patients in two cohorts. The study patients will receive 5 cycles of 4 weekly infusions.
Interventions
This study is a First in Human, open label, SAD and MAD study to determine the safety and PK characteristics of mEphA4-Fc in HVs and patients with ALS. Measurements of clinical and lung function endpoints associated with ALS will also be assessed.
There will be two parts:
Part 1 (SAD) of the study will be conducted in five cohorts of 4 subjects each.
The MAD part of the study will be conducted in two cohorts of 4 ALS patients each.
Investigational Product (IP): mEphA4-Fc
Presentation: Liquid in
This study is a First in Human, open label, SAD and MAD study to determine the safety and PK characteristics of mEphA4-Fc in HVs and patients with ALS. Measurements of clinical and lung function endpoints associated with ALS will also be assessed. There will be two parts: Part 1 (SAD) of the study will be conducted in five cohorts of 4 subjects each. The MAD part of the study will be conducted in two cohorts of 4 ALS patients each. Investigational Product (IP): mEphA4-Fc Presentation: Liquid in a Glass vial: 10 mL at 10 mg/mL Mode of administration: Intravenous (IV) infusion mEphA4-Fc will be administered as an IV infusion in a 0.9% sodium chloride solution (normal saline). Each infusion of mEphA4-Fc administration should be completed within 75-90 minutes. Part 1 (SAD) in Healthy Volunteers: Each cohort will be comprised of 4 HVs each to receive mEphA4-Fc. mEphA4-Fc will be given in sequential, escalating doses; Incremental doses starting from a dose selected according to the NOAEL strategy for FIH studies will be administered and the planned increments will not exceed 3 fold. The minimum and maximum doses for each cohort are limited by body weight. The actual dose level for a cohort will be ultimately decided by the Safety Review Committee based on a review of data from the proceeding cohort/s. Part 2 (MAD) in ALS Patients: The first multiple dose cohort may be initiated prior to the completion of the fifth SAD cohort and after completion of the fourth SAD cohort. The multiple ascending dose will be comprised of two cohorts of 4 ALS patients each to receive mEphA4-Fc. The frequency of administration, dose increments and number of cohorts will be reviewed based on review of all data by the Safety Review Committee. Each cohort will be comprised of 4 subjects each to receive 4 doses of mEphA4-Fc, over 28 days. The proposed time duration between each dose will be 7 days, but will be reviewed by the Safety Review Committee. To monitor adherence to the intervention for all SAD/MAD cohorts: Clinical trial management system, laboratory tests, and pharmacy records. Part 1: 1mg/kg, 3mg/kg, 10mg/kg, 20 mg/kg, 30 mg/kg Part 2: 15mg/kg, 30mg/kg Part 3(Extended Access Study) in ALS Patients. Total of 8 ALS patients in 2 cohorts. The study patients will receive 5 cycles of 4 weekly infusions. Part 3 will involve 4 infusions of 15 / 20 or 30 mg/kg weekly, in a 4-week cycle, for up to 6 months. Each dose of mEphA4-Fc will be given as an IV infusion over 90 to 120 minutes. The 4 infusions will take place 7 days apart, at Day 1, 8,15, 22, or until intolerable toxicity, progression of disease, or withdrawal of consent. Therefore, all subjects will have been dosed for 6 cycles for up to 6 months when they complete the Phase 1b study. All MAD subjects who want to continue receiving mEphA4-Fc treatment will be directly moved to Part 3. So, the cohorts in Part 2 will be unique cohorts in Part 3. The first dose of Part 3 would be 7 days post the last dose of the MAD part 2. Part 3 addition was anticipated prior to enrolment commencement for Part 2, but has been implemented post enrolment given the same subjects are involved in Parts 2 and 3.
Sponsors
NuNerve Pty. Ltd.
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy Volunteers: 1. Healthy male or female volunteers aged 18 to 55 years of age (inclusive at the time of informed consent). 2. Subjects must be in good general health, with no significant medical history, have no clinically significant abnormalities on physical examination at Screening and/or before administration of the initial dose of study drug. 3. Subjects must have a minimum body weight of 50 kg and a Body Mass Index (BMI) between greater than or equal to 18.0 and lesser than or equal to 32.0 kg/m2 at Screening. 4. Subjects must have clinical laboratory values within normal range as specified by the testing laboratory, unless deemed not clinically significant by the Investigator or delegate. 5. Subjects who smoke no more than 2 cigarettes or equivalent per week can be included in the study but must be willing to abstain from smoking during the confinement period. ALS Patients; 1. Males and females aged 18 to 70 years of age (inclusive at the time of informed consent). 2. Must have a minimum body weight of 50 kg and a BMI between greater than or equal to 18.0 and less than or equal to 32.0 kg/m2 at Screening. 3. Patients who smoke no more than 2 cigarettes or equivalent per week can be included in the study but must be willing to abstain from smoking during the confinement period. 4. Patients with diagnosis of familial or sporadic ALS, defined as meeting the possible, laboratory-supported probable, probable, or definite diagnosis of ALS according to modified El Escorial criteria. 5. Onset of muscle weakness within 60 months of study entry.
Exclusion criteria
Healthy Volunteers: 1. Females of childbearing potential, pregnant (confirmed by serum or urine beta human chorionic gonadotropin (ßhCG) test at Screening and prior to dosing) or lactating or planning to become pregnant (self or partner) at any time during the study, including the follow-up period. 2. Prior or ongoing medical conditions, medical history, physical findings, or laboratory abnormality that, in the Investigator’s (or delegate’s) opinion, could adversely affect the safety of the subject. 3. Presence of any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the subject will comply with the protocol or complete the study per protocol. 4. A history of substance abuse or dependency or history of recreational IV drug use over the last 5 years (by self-declaration). 5. Blood donation or significant blood loss within 60 days prior to the first study drug administration. ALS Patients: 1. Patients with other neuromuscular disorders (in addition to their ALS diagnosis), unless the Investigator determines that such additional disorder will not affect safety or other measures in this study. 2. Patients with frontotemporal dementia (FTD). 3. Patients with evidence of psychiatric illness or impaired cognitive function which, in the Investigator’s opinion, is likely to prevent them from a full understanding of and/or compliance with the study requirements and procedures. 4. Patients with abnormalities detected during the Screening evaluations which, in the Investigator’s medical judgement, are sufficiently significant to exclude them from participation in the study. 5. Patients with Type I or poorly controlled Type II Diabetes Mellitus (HbA1c greater than 8%).
Outcome results
None listed