First-In-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALT-100

NCT05426746 | Completed Phase 1 FDA Drug

• 1 other identifier: ALT-100-001
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

ALT-100 is a monoclonal antibody developed by Aqualung Therapeutics Corp. as a treatment for Acute Respiratory Distress Syndrome (ARDS). ARDS can occur as a serious complication in patients with respiratory infections such as COVID-19 and Influenza or have acquired trauma to their lungs. 32 healthy male or female participants between the ages of 18 and 55 years will be enrolled into 4 cohorts of single ascending doses. The doses being investigated are 0.1mg/kg, 0.4mg/kg, 1mg/kg and 4mg/kg administered by intravenous infusion. Participants will be screened within 28 days of study treatment, be admitted to the clinical research unit for 3 nights and attend 7 outpatient visits on study days 8, 15, 22, 29, 60, 90 and 120 respectively. This study will collect data to evaluate safety and tolerability, Pharmacokinetics of ALT-100, Pharmacodynamics of ALT-100 and determine if Anti-drug Antibodies are produced in the participants.

Conditions

ARDS, Human

Keywords

Respiratory Distress Syndrome

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability will be assessed by the incidence, frequency and dose-relationship of all adverse events

  up to 120 days post ALT-100 infusion

Secondary Outcomes (12)

• Plasma PK Parameter: Area under concentration-time curve from time 0 (pre-dose) to the last quantifiable data point (AUC0-t)

  at 10, 20, 30, 45 minutes, and 1, 2, 4, 8, hours post start of ALT-100 infusion and on Days 2, 3, 8. 15, 22, 29, 60, 90 and 120.

• Plasma PK Parameter: Area under concentration-time curve from time 0 (pre-dose) extrapolated to infinity point (AUC0-infinity)

  at 10, 20, 30, 45 minutes, and 1, 2, 4, 8, hours post start of ALT-100 infusion and on Days 2, 3, 8. 15, 22, 29, 60, 90 and 120.

• Plasma PK Parameter:: Maximum measured drug concentration (Cmax)

  at 10, 20, 30, 45 minutes, and 1, 2, 4, 8, hours post start of ALT-100 infusion and on Days 2, 3, 8. 15, 22, 29, 60, 90 and 120.

• Plasma PK Parameter: Dose normalised Cmax (determined by Cmax/dose [D]) and dose normalised AUC determined by AUC/D)

  at 10, 20, 30, 45 minutes, and 1, 2, 4, 8, hours post start of ALT-100 infusion and on Days 2, 3, 8. 15, 22, 29, 60, 90 and 120.

• Plasma PK Parameter: The percent of the AUC from time 0 (pre-dose) extrapolated to infinity determined by AUC/D) (%AUCextrap)

  at 10, 20, 30, 45 minutes, and 1, 2, 4, 8, hours post start of ALT-100 infusion and on Days 2, 3, 8. 15, 22, 29, 60, 90 and 120.

Other Outcomes (4)

• Changes from baseline in cellular response with ALT-100 compared to placebo, as assessed by peripheral circulating neutrophil counts in whole blood

  at 6, 24, and 48 hours, and 7, 14 and 28 days following ALT-100 treatment

• Changes from baseline in cellular response with ALT-100 compared to placebo, as assessed by peripheral circulating monocyte counts in whole blood

  at 6, 24, and 48 hours, and 7, 14 and 28 days following ALT-100 treatment

• Changes from baseline in cellular response with ALT-100 compared to placebo, as assessed by peripheral circulating lymphocyte counts in whole blood

  at 6, 24, and 48 hours, and 7, 14 and 28 days following ALT-100 treatment

Study Arms (2)

ALT-100

EXPERIMENTAL

one of 4 ascending dose levels of ALT-100 administered as a single intravenous infusion with a staggered dose for sentinels followed by the rest of the cohort. cohort 1: 0.1 mg/kg cohort 2: 0.4 mg/kg cohort 3: 1.0 mg/kg cohort 4: 4.0 mg/kg

Drug: ALT-100

Saline

PLACEBO COMPARATOR

normal sterile saline (0.9% sodium chloride) administered as a single intravenous infusion at a constant infusion rate in a total volume and appearance matched to the active comparator, with a staggered dose for sentinels followed by the rest of the cohort

Other: Normal Saline

Interventions

ALT-100 DRUG

intravenous infusion of drug substance diluted in 0.9% normal sterile saline

ALT-100

Normal Saline OTHER

intravenous infusion of placebo (0.9% normal sterile saline)

Saline

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female between 18 and 55 years of age, inclusive.
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, safety laboratory tests and cardiac monitoring at screening and admission. Potential participants with a history of childhood asthma (resolved), depression (non-hospitalised, but potentially medicated in the past) and migraine may be considered for study participation. A potential participant with a clinical abnormality or laboratory parameters outside the normal reference range for the population being studied may be rescreened once, at the Investigator's discretion, and may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. The Investigator may discuss with the local MM and Sponsor medical representative as required.
• Normal vital signs after greater than or equal to 5 minutes resting in a supine or semi-supine position:
• greater than 90 mmHg and less than 160 mmHg systolic blood pressure (SBP)
• greater than 50 mmHg and less than 95 mmHg diastolic blood pressure (DBP)
• greater than 45 bpm and less than 100 bpm heart rate (HR)
• Body temperature greater than or equal to 35.5°C to less than or equal to 37.7°C
• Standard 12-lead ECG parameters after greater than or equal to 5 minutes resting in a supine or semi-supine position with PR greater than 120 msec and less than 220 msec, QRS less than 120 msec, QT Interval with Fridericia's Correction (QTcF) less than or equal to450 msec for males and less than or equal to 470 msec for females, and otherwise normal ECG.
• Normal creatinine clearance values (\>60 mL/min) at screening (calculated from serum creatinine by a predicting equation using Cockcroft-Gault formula), normal serum creatinine value as defined by the local reference laboratory, normal urine microscopy and no significant proteinuria on dipstick testing.
• Body weight greater than or equal to 50 kg and BMI in the range 18 kg/m2 - 32 kg/m2 (inclusive).
• Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or use highly effective contraceptive method (oral contraceptive pills \[OCPs\], long-acting implantable hormones, injectable hormones, a vaginal ring or an intrauterine device \[IUD\]) from screening until study completion, including the follow up period for at least 30 days after the last dose of study drug, or be post-menopausal for greater than or equal to 12 months. Post-menopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) levels (greater than or equal to 40 IU/L) at screening for amenorrheic female participants. Female participants who's only partner has had a vasectomy, and female participants who are abstinent from heterosexual intercourse as part of their usual lifestyle will also be eligible for participation.
• Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and admission and be willing to have additional pregnancy tests as required throughout the study.
• Males must be surgically sterile (greater than 30 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a WOCBP, the male participant and his partner must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) and/ or using an acceptable, highly effective contraceptive method from screening until study completion, including the follow up period, for at least 90 days after the last dose of study drug. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner (WOCBP) that includes: OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring or an IUD. Male participants whose female partner is post-menopausal, and participants who are abstinent from heterosexual intercourse as part of their usual lifestyle will also be eligible.
• Male participants must agree to refrain from donating sperm from screening until study completion, including the follow up period, for at least 90 days after the last dose of study drug.
• Provides written informed consent and is willing and able to undergo all study procedures and attend the scheduled follow up visit/s per protocol

You may not qualify if:

• A positive reverse transcriptase polymerase chain reaction (RT-PCR) test or rapid antigen test (RAT), as applicable, for influenza A/B or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) at screening or at time of admission to the CRU.
• Note: A nose and/or throat swab or saliva sample may be collected and analysed for COVID-19 at screening, and at one or multiple timepoints during the study as per local, state and national guidelines and per the standard practice at the CRU.
• A history of Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV) infection and/or a positive pre-study HIV, Hepatitis B surface antigen (HbsAg), total Hepatitis B core antibody (HBcAb), or positive Hepatitis C virus (HCV) antibody result within 3 months of screening
• Impaired hepatic function as indicated by screening aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than or equal to 2 or total bilirubin greater than or equal to 1.5 x upper limit of normal (ULN), which remains above these limits if retested (i.e., due to a slightly elevated initial result or abnormalities in synthetic liver function tests that are judged by the Investigator to be clinically significant)
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of known Gilbert's syndrome or asymptomatic gallstones).
• Any other serious medical condition or abnormality that, in the Investigator's judgement, precludes the participant's safe participation in and completion of the study.
• A positive pre-study drug or alcohol screen. A positive drug or alcohol screen test result may be verified by re-testing (up to 1 false positive result permitted) and may be followed up at the discretion of the Investigator.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of greater than 21 units for males or greater than 14 units for females. One unit is equivalent to 10 g of alcohol and the following can be used as a guide: a half-pint (\~240 ml) of beer, 1 glass (125 mL) of wine or 1 (30 mL) measure of spirits.
• The participant is unwilling to abstain from alcohol consumption from 24 hours prior to dosing until discharge from the CRU, and for 24 hours prior to all other outpatient visits to the CRU.
• The participant is unwilling to abstain from smoking while domiciled at the CRU.
• Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human or humanised antibodies, fusion proteins, ALT-100 excipients, or a history of drug or other allergy including severe allergic reaction that in the opinion of the Investigator, local MM or Sponsor medical representative, contraindicates their participation.
• Participants receiving more than 2 weeks' treatment with immunosuppressive agents, excluding topical steroids, in the previous 3 months.
• Participation in a clinical trial within 30 days before randomisation; use of any experimental therapy within 30 days or 5 half-lives prior to randomisation, whichever is greater; or use of any biologic therapy within 12 weeks or 5 half-lives prior to randomisation, whichever is greater.
• Participants having received any type of vaccination within 2 weeks of the anticipated dosing event or are expected to be vaccinated within 2 weeks post-dosing.
• Use of prescription or non-prescription drugs (except simple analgesics and topical steroids), including vitamins, herbal and dietary supplements (including St John's Wort) within 2 weeks or 5 half-lives (whichever is longer) prior to the first dose of study drug, unless in the opinion of the Investigator, local MM and Sponsor medical representative the medication will not interfere with the study procedures or compromise participant safety.

Sponsors & Collaborators

• Aqualung Therapeutics Corp.: lead

Study Sites (1)

CMAX Clinical Research Pty Ltd

Adelaide, South Australia, 5000, Australia

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Joe GN Garcia, MD

  Aqualung Therapeutics

  STUDY DIRECTOR

• Thomas M Polasek, MBBS

  CMAX Clinical Research Pty Ltd

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Site, Clinical Research Organization and Sponsor personnel are are blinded except for unblinded pharmacist staff, unblinded Project Manager, unblinded Monitor and unblinded statistician
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: First in human, randomized, double-blind, placebo-controlled, multi-cohort healthy volunteer trial

Study Record Dates

• First Submitted: June 13, 2022
• First Posted: June 22, 2022
• Study Start: July 5, 2022
• Primary Completion: May 18, 2023
• Study Completion: May 18, 2023
• Last Updated: September 14, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)