Amyotrophic Lateral Sclerosis, Parkinson Disease
Conditions
Keywords
Parkinsons, ALS
Brief summary
The purpose of this research study is to assess safety and tolerability of a single intravenous (given through a vein) dose of the investigational retinal tracer AMDX-2011P in patients with neurodegenerative diseases (Parkinson's disease and ALS).
Detailed description
The primary objective of this study is to evaluate the safety and tolerability of three different doses of AMDX-2011P (25mg, 50mg, or 100mg) given as a single intravenous dose in patients with neurodegenerative diseases (Parkinson's disease and ALS). The first cohort of participants taking part in the study will receive the lowest dose of AMDX-2011P (25mg). If no major side effects occur, the dose will be increased for the next group of participants to 50mg and then to 100mg. Secondary objective of this study is to characterize the pharmacokinetic (PK) profile of AMDX-2011P and AMDX-2011. Exploratory evaluations of the biological activity of AMDX-2011P in the retina will be performed by imaging.
Interventions
DRUGAMDX2011P
AMDX2011P single bolus injection intravenous for diagnostic review
Sponsors
Amydis Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Dose escalating via Cohorts total 1-3 cohorts
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For Subjects with Parkinson's Disease 1. Clinically established Parkinson's disease based on Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson's disease (Table 8) and a modified Hoehn & Yahr scale of 1-3 (Table 9). 2. No suspected atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis, or degenerative diseases. For Subjects with ALS 3. Confirmed diagnosis of ALS with both upper and lower motor neuron involvement. For All Subjects 4. Ability to undergo retinal imaging. 5. Subject or legally authorized representative must provide signed informed consent (or signed assent form) prior to study entry and have the ability and willingness to attend and comply with the necessary study procedures and visits at the study site. For subjects unable to physically sign the informed consent, a guardian or trusted care giver can sign on their behalf in presence of an independent witness. 6. Contraception use by study subjects of childbearing potential (male and female) and female partners of childrearing potential male subjects should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Exclusion criteria
1. Presence of any underlying physical or psychological medical condition that would make it unlikely that the subject will complete the study per protocol. 2. Clinically significant laboratory abnormalities assessed by the investigator. 3. Active malignancy and/or history of malignancy in the past 5 years, with the exception of completely excised non-melanoma skin cancer or low-grade cervical intraepithelial neoplasia. 4. Prolonged QTcF (\>450 ms for males and \>470 ms for females), cardiac arrhythmia, or any clinically significant abnormality in the resting ECG, as judged by the investigator. 5. Presence of any ocular condition that would significantly hinder the ability to detect and quantify hyper-fluorescent puncta (e.g., eyes with significant hyper-autofluorescence that would mask the ability to detect, quantify, and discern post-injection hyper-fluorescent signal from pre-injection hyper-autofluorescence signal). 6. Use of any new prescription therapies or vaccines within 7 days prior to the study drug administration. 7. Drugs with potential phototoxicity per Package Insert are prohibited within 48 hours or 5 half-lives, whichever is longer, prior to first study drug until End-of-study (EOS) visit, except for those required for treatment of underlying disease. 8. Administration of investigational product in another study within 30 days prior to the first study drug administration, or five half-lives, whichever is longer. 9. Females who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AMDX-2011P Adverse Events Profile | 1 week | Incidence of Treatment Emergent Adverse Events (TEAEs) at for each cohort (dose level). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Analysis of AMDX-2011P | 8 hours | Area under the plasma concentration versus time curve (AUC) |
| Concentration of AMDX-2011P | 8 hours | Peak Plasma Concentration (Cmax) |
Countries
United States
Participant flow
Recruitment details
13 subjects: 3 in Cohort 1 (25mg dose) 4 in Cohort 2 (50mg dose) 6 in Cohort 3 (100mg dose)
Participants by arm
| Arm | Count |
|---|---|
| AMDX2011P 25mg 25mg (1ml) single bolus injection intravenous for diagnostic review | 3 |
| AMDX2011P 50mg AMDX2011P 50mg (2ml) single bolus injection intravenous for diagnostic review | 4 |
| AMDX2011P 100mg AMDX2011P 100mg (4ml) single bolus injection intravenous for diagnostic review | 6 |
| Total | 13 |
Baseline characteristics
| Characteristic | AMDX2011P 25mg | AMDX2011P 50mg | AMDX2011P 100mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 6 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 4 | 0 / 6 |
| other Total, other adverse events | 0 / 3 | 1 / 4 | 3 / 6 |
| serious Total, serious adverse events | 0 / 3 | 0 / 4 | 0 / 6 |
Outcome results
Primary
AMDX-2011P Adverse Events Profile
Incidence of Treatment Emergent Adverse Events (TEAEs) at for each cohort (dose level).
Time frame: 1 week
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AMDX2011P 25mg | AMDX-2011P Adverse Events Profile | 0 Treatment Emergent Adverse Events TEAEs |
| AMDX2011P 50mg | AMDX-2011P Adverse Events Profile | 1 Treatment Emergent Adverse Events TEAEs |
| AMDX2011P 100mg | AMDX-2011P Adverse Events Profile | 3 Treatment Emergent Adverse Events TEAEs |
Secondary
Concentration of AMDX-2011P
Peak Plasma Concentration (Cmax)
Time frame: 8 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AMDX2011P 25mg | Concentration of AMDX-2011P | 4400 ng/mL | Standard Deviation 572 |
| AMDX2011P 50mg | Concentration of AMDX-2011P | 16600 ng/mL | Standard Deviation 15800 |
| AMDX2011P 100mg | Concentration of AMDX-2011P | 14600 ng/mL | Standard Deviation 3890 |
Secondary
Pharmacokinetic Analysis of AMDX-2011P
Area under the plasma concentration versus time curve (AUC)
Time frame: 8 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AMDX2011P 25mg | Pharmacokinetic Analysis of AMDX-2011P | 706 h*ng/mL | Standard Deviation 110 |
| AMDX2011P 50mg | Pharmacokinetic Analysis of AMDX-2011P | 3170 h*ng/mL | Standard Deviation 3290 |
| AMDX2011P 100mg | Pharmacokinetic Analysis of AMDX-2011P | 2330 h*ng/mL | Standard Deviation 637 |