About this trial

The goal of this clinical trial is to learn if ASCT-83 is safe and well-tolerated and measure how ASCT-83 is absorbed, distributed, and eliminated from the body over time. The study will be conducted in healthy adults.

The main questions this study will answer are:

* Is ASCT-83 safe at clinical doses? * Does ASCT-83 have side effects at clinical doses? * How is ASCT-83 absorbed, distributed, and eliminated from the body? Researchers will compare ASCT-83 to a placebo (a look-alike substance that contains no drug).

The study has two parts: participants in Part 1 will receive only one dose of ASCT-83 or placebo participants in Part 2 will receive one dose of ASCT-83 or placebo a day for 7 days. Participants will visit the clinic to take ASCT-83 or placebo, to receive health checkups and undergo health tests. Participants in Part 1 will spend 5 days/4 nights in the clinic, participants in Part 2 will spend 11 days/10 nights in the clinic. In addition, there will be up to 3 outpatient visits.

The results of this study will help determine safe dose levels and support the design of future clinical trials.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

be medically healthy based on medical history, physical exam, labs, and ECG

be 18-64 years (inclusive)

at screening, have a body mass index (BMI) > 19 to < 35 kg/m²

be willing and able to understand and voluntarily sign an informed consent

Disqualifiers

are a study site staff, Alcamena employee or immediate family member, or have participated in another clinical trial within 30 days or 5 half-lives of a prior investigational product.

have evidence of liver disease or abnormal liver tests (ALT/AST, Alk Phos, GGT, or bilirubin > ULN); positive hepatitis B or C serology (people with Gilbert syndrome may be included).

have a history of kidney disease, protein in the urine or reduced kidney function based on screening blood tests.

have a history of cancer with active disease, suspected relapse, treatment within 6 months, or ongoing therapy affecting immune, liver, or kidney function.

Trial design

Design model

Sequential

Treatments tested in this trial

ASCT-83
Drug
ASCT-83 is a 23-amino acid, macrocyclic peptide with a molecular weight of approximately 3 kilodaltons under development for the treatment of neuropathic pain (NeP). ASCT-83 25 mg/mL sterile solution for injection consists of 25 mg of ASCT-83 drug substance dissolved in 1 mL of histidine buffer. The product also contains mannitol to adjust the osmolarity of the final product. The product is stored at -20°C prior to dilution to achieve the target dose.
Placebo
Drug
Placebo solution contaninig the same histidine buffer and mannitol concentrations as ASCT-83, with polyoxyl 35 castor oil (0.1% w/v) added to match the appearance of the active solution.

Treatment groups

72 Participants

are divided into 11 treatment groups

11

Treatment groups

See each treatment group below.

Group A: SAD-PlaceboPlacebo comparator 1 intervention

Group B: SAD, ASCT-83 dose 1Experimental treatment 1 intervention

Group C: SAD, ASCT-83 dose 2Experimental treatment 1 intervention

Group D: SAD-ASCT dose 3Experimental treatment 1 intervention

Group E: SAD-ASCT dose 4Experimental treatment 1 intervention

Group F: SAD, ASCT-83 dose 5Experimental treatment 1 intervention

Group G: SAD, ASCT-83 dose 6Experimental treatment 1 intervention

Group H: MAD-PlaceboPlacebo comparator 1 intervention

Group I: MAD, ASCT-83 dose 1Experimental treatment 1 intervention

Group J: MAD, ASCT-83 dose 2Experimental treatment 1 intervention

Group K: MAD, ASCT-83 dose 3Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Incidence, severity and dose relationships of Treatment-Emergent Adverse Events (TEAEs) and non-TEAEs, Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), premature treatment and study discontinuation due to Adverse Events (AEs)

The investigator will assess and record information pertaining to the AE, which includes but is not limited to the following: date of onset, event diagnosis (when known) and/or signs and symptoms, duration, severity, seriousness (i.e. serious adverse event or not serious), expected/unexpected, and relationship to the study therapy or procedure, action(s) taken, and outcome. Severity grading: 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental ADL. 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. 4 Life-threatening consequences; urgent intervention indicated. 5 Death related to AE.

Time frame

Single dose part of the study: from enrollment to 30-32 days after the end of treatment. Multiple dose part of the study: from enrollment to 36-38 days after the end of treatment.

2

Incidence and severity of changes in clinical safety parameters, including vital signs (including body weight), laboratory (including markers of inflammation), ECG results, and skin assessments (including injection site reactions).

Time frame

Single dose part of the study: from enrollment to 30-32 days after the end of treatment. Multiple dose part of the study: from enrollment to 36-38 days after the end of treatment.

3

Incidence of suicidality

Suicide risk will be assessed through a questionnaire (Columbia-Suicide Severity Rating Scale (C-SSRS)). A score ≥4 is considered suicidal ideation.

Time frame

Single dose part of the study: from enrollment to 30-32 days after the end of treatment. Multiple dose part of the study: from enrollment to 36-38 days after the end of treatment.

4

Incidence and type of abnormal skin assessments, including injection-site reactions.

The FDA Toxicity Grading Scale (TGS) for injection/vaccine sites will be used: Mild/Grade 1, Moderate/Grade 2, Severe/Grade 3, Life-threatening/Grade 4.

Time frame

Single dose part of the study: from enrollment to 30-32 days after the end of treatment. Multiple dose part of the study: from enrollment to 36-38 days after the end of treatment.

Secondary outcomes

1

Area under the concentration-time curve from time zero to infinity (AUC0-inf) of ASCT-83

Plasma concentration of ASCT-83 will be measured following a single dose of ASCT-83 (SAD part of the study) or multiple doses of ASCT-83 (MAD part of the study) to characterize the total exposure to ASCT-83.

Time frame

SAD: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours post-dose. MAD: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1; pre-dose on Days 3 to 7; 24, 36, 48, and 72 hours after the final dose on Day 7

2

Area under the concentration-time curve from time zero to 24 h (AUC0-24h) of ASCT-83

Plasma concentration of ASCT-83 will be measured following a single dose of ASCT-83 (SAD part of the study) or multiple doses of ASCT-83 (MAD part of the study) to characterize exposure to ASCT-83 over the last 24 h dosing interval.

Time frame

SAD: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours post-dose. MAD: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1; pre-dose on Days 3 to 7; 24, 36, 48, and 72 hours after the final dose on Day 7

3

Peak plasma concentration (Cmax) of ASCT-83

Plasma concentration of ASCT-83 will be measured to characterize the peak concentration of ASCT-83 in the blood following either a single dose (SAD part of the study) or multiple doses (MAD part of the study) of ASCT-83.

Time frame

SAD: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours post-dose. MAD: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1; pre-dose on Days 3 to 7; 24, 36, 48, and 72 hours after the final dose on Day 7

4

Time to reach maximum plasma concentration (Tmax) of ASCT-83

Plasma concentrations of ASCT-83 will be measured to determine the time at which the highest concentration of ASCT-83 is reached after either a single dose (SAD part of the study) or multiple doses of ASCT-83 (MAD part of the study).

Time frame

SAD: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours post-dose. MAD: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1; pre-dose on Days 3 to 7; 24, 36, 48, and 72 hours after the final dose on Day 7

Other outcomes

1

Quantification of Pharmacodynamic (PD) Biomarkers of Target Engagement: SMAD1/5/8

Single dose part of the study (SAD): Phospho-SMAD1/5/8 levels will be measured in Peripheral Blood Mononuclear Cells (PBMCs) following ex vivo BMP4 stimulation. Multiple dose part of the study (MAD): total SMAD1/5/8 depletion will be measured in unstimulated PBMC lysates.

Time frame

SAD: pre-dose on Day 1 and 24 hours after dosing (Day 2). MAD: pre-dose on Day 1 and 4 hours after the third and last dosing.

2

Quantification of Pharmacodynamic (PD) Biomarkers of Target Engagement: BDNF

The change from baseline levels in the amount of Brain-Derived Neurotrophic Factor (BDNF) circulating in the blood will be measured in plasma after a single dose of ASCT-83.

Time frame

SAD: pre-dose on Day 1 and 24 hours after dosing (Day 2). MAD: pre-dose on Day 1 and 4 hours after the third and last dosing.

Safety, Tolerability, and Pharmacokinetics of ASCT-83 in Healthy Adults

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

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