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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05426746




Registration number
NCT05426746
Ethics application status
Date submitted
13/06/2022
Date registered
22/06/2022

Titles & IDs
Public title
First-In-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALT-100
Scientific title
A First-in-human, Phase 1, Randomised, Placebo-controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of Intravenously Infused ALT-100 in Healthy Volunteers
Secondary ID [1] 0 0
ALT-100-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ARDS, Human 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ALT-100
Other interventions - Normal Saline

Experimental: ALT-100 - 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

Placebo comparator: Saline - 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


Treatment: Drugs: ALT-100
intravenous infusion of drug substance diluted in 0.9% normal sterile saline

Other interventions: Normal Saline
intravenous infusion of placebo (0.9% normal sterile saline)
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability will be assessed by the incidence, frequency and dose-relationship of all adverse events
Timepoint [1] 0 0
up to 120 days post ALT-100 infusion
Secondary outcome [1] 0 0
Plasma PK Parameter: Area under concentration-time curve from time 0 (pre-dose) to the last quantifiable data point (AUC0-t)
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
Plasma PK Parameter: Area under concentration-time curve from time 0 (pre-dose) extrapolated to infinity point (AUC0-infinity)
Timepoint [2] 0 0
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.
Secondary outcome [3] 0 0
Plasma PK Parameter:: Maximum measured drug concentration (Cmax)
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
Plasma PK Parameter: Dose normalised Cmax (determined by Cmax/dose [D]) and dose normalised AUC determined by AUC/D)
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Plasma PK Parameter: The percent of the AUC from time 0 (pre-dose) extrapolated to infinity determined by AUC/D) (%AUCextrap)
Timepoint [5] 0 0
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.
Secondary outcome [6] 0 0
Plasma PK Parameter: Time of maximum concentration (Tmax)
Timepoint [6] 0 0
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.
Secondary outcome [7] 0 0
Plasma PK Parameter: Terminal elimination rate constant (kel)
Timepoint [7] 0 0
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.
Secondary outcome [8] 0 0
Plasma PK Parameter: Elimination half-life (T½)
Timepoint [8] 0 0
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.
Secondary outcome [9] 0 0
Plasma PK Parameter: Total body clearance (CL)
Timepoint [9] 0 0
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.
Secondary outcome [10] 0 0
Plasma PK Parameter: Volume of distribution at the terminal phase (Vz)
Timepoint [10] 0 0
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.
Secondary outcome [11] 0 0
Plasma PK Parameter: Dose normalised Cmax (determined by Cmax/dose [D]) and dose normalised AUC (determined by AUC/D)
Timepoint [11] 0 0
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.
Secondary outcome [12] 0 0
Serum Immunogenicity: To investigate the presence of antibodies that bind to ALT-100, and if detected, to initiate characterisation of these anti-ALT-100 antibodies (anti-drug antibodies; ADA).
Timepoint [12] 0 0
Presence of ADA in serum on Days 8, 15, 29, 60, 90 and 120 days following ALT-100 treatment

Eligibility
Key inclusion criteria
1. Male or female between 18 and 55 years of age, inclusive.
2. 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.
3. Normal vital signs after greater than or equal to 5 minutes resting in a supine or semi-supine position:

1. greater than 90 mmHg and less than 160 mmHg systolic blood pressure (SBP)
2. greater than 50 mmHg and less than 95 mmHg diastolic blood pressure (DBP)
3. greater than 45 bpm and less than 100 bpm heart rate (HR)
4. Body temperature greater than or equal to 35.5°C to less than or equal to 37.7°C
4. 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.
5. 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.
6. Body weight greater than or equal to 50 kg and BMI in the range 18 kg/m2 - 32 kg/m2 (inclusive).
7. 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.
8. 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.
9. 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.
10. Provides written informed consent and is willing and able to undergo all study procedures and attend the scheduled follow up visit/s per protocol
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. 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.
2. 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
3. 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)
4. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of known Gilbert's syndrome or asymptomatic gallstones).
5. 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.
6. 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.
7. 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.
8. 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.
9. The participant is unwilling to abstain from smoking while domiciled at the CRU.
10. 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.
11. Participants receiving more than 2 weeks' treatment with immunosuppressive agents, excluding topical steroids, in the previous 3 months.
12. 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.
13. 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.
14. 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.
15. Pregnant or breastfeeding WOCBP
16. Donation within the last 3 months of whole blood (greater than 499 mL) and/ or within 2 weeks of plasma.
17. Participant unable to provide written informed consent.
18. Unwilling or unable to follow protocol requirements, including attendance at follow up visit/s.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/05/2023
Sample size
Target
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Aqualung Therapeutics Corp.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Joe GN Garcia, MD
Address 0 0
Aqualung Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05426746