First-In-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALT-100
Condition: ARDS, Human
MeSH terms: Respiratory Distress Syndrome
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      Inflammation is a key feature in the pathogenesis of sepsis and ARDS. The investigational
      product (IP), ALT-100, is a humanised murine mAb that binds specifically to eNAMPT, a novel
      therapeutic target for ARDS and ARDS associated ventilator-induced lung injury (VILI).
      ALT-100 is proposed for development as a potential treatment for patients with ARDS and VILI.

      This is a first-in-human (FIH), Phase 1, randomised, double-blind, placebo-controlled study
      to investigate the safety, tolerability, and PK profile of single ascending doses of IV
      infused ALT-100 administered in healthy participants. The PD effects of ALT-100 will also be
      explored.

      The Single ascending dose escalation study will be conducted in approximately 32 evaluable
      participants who will be sequentially enrolled and randomised in a 3:1 ratio (active:
      placebo) to one of 4 planned single ascending dose (SAD) cohorts:

        -  Cohort 1: 0.1 (mg/kg) ALT-100 (6 participants)/ Placebo (2 participants)

        -  Cohort 2: 0.4 (mg/kg) ALT-100 (6 participants)/ Placebo (2 participants)

        -  Cohort 3: 1.0 (mg/kg) ALT-100 (6 participants)/ Placebo (2 participants)

        -  Cohort 4: 4.0 (mg/kg) ALT-100 (6 participants)/ Placebo (2 participants)

      A sentinel dosing strategy will be utilised for the first 2 participants (n=1 active; n=1
      placebo) in each dosing cohort. Sentinel participants will receive study drug at least 14
      days before the remainder of participants in the cohort. In the absence of clinically
      significant safety signals in sentinel participants over the 14-day post-treatment
      observation period (up to and including the Day 15 visit, as determined by the Investigator,
      in consultation with the local medical monitor (MM) and Sponsor if required), the remainder
      of participants in the cohort may proceed to be admitted, randomised and dosed, at the
      Investigator's discretion, with a sufficient minimum interval between all subsequent
      participants to allow monitoring of any acute post-dose safety events.

      Screening (Day -29 to Day -2) and Admission (Day -1): Screening for the study will occur
      within 28 days prior to enrolment and admission on Day -1 to the clinical research unit
      (CRU). Informed consent must be documented before any study-specific procedure, including for
      screening, is performed. Consenting participants who meet all the eligibility criteria at
      screening will be enrolled upon confirmation of their eligibility at the time of admission to
      the CRU on Day -1. Participants will be randomised on the morning of Day 1 to receive ALT-100
      or placebo by IV infusion. All participants will undergo baseline assessments prior to
      administration of study treatment on Day 1. Screening and baseline assessments are outlined
      in the Schedule of Assessments (SOA).

      Treatment (Day 1): Randomised study participants will be administered a single IV infusion of
      study drug per their assigned treatment on Day 1. Following study drug administration on Day
      1, all participants will remain confined at the CRU and will undergo safety, PK, PD and other
      assessments, per the Schedule of Assessments.

      In the absence of clinically significant safety signals, and at the Investigator's
      discretion, participants will be discharged from the CRU on Day 3 following completion of all
      specified assessments.

      Participants will return to the CRU on an outpatient basis on Day 8 (±1 day), Day 15 (±1
      day), Day 22 (±2 days), Day 29 (±3 days), Day 60 (±7 days), Day 90 (±7 days) and at Day 120
      (±7 days) for safety and other assessments.

      Additional unscheduled visits may occur at the Investigator's discretion, i.e., if considered
      necessary for clinical safety reasons

      The Day 120 visit will constitute the end of study participation. A participant will be
      considered to have completed the study following completion of all assessments at the Day 120
      visit.

      Early termination: In the case of premature discontinuation from the study, participants will
      return to the CRU and complete an early termination (ET) visit. For participants who withdraw
      prior to Day 29, assessments conducted at the ET visit will be as described for the onsite
      visit on Day 29 (±3 days). For participants who withdraw after Day 29, assessments conducted
      at the ET visit will be as described for the onsite visit on Day 120 (±7 days). All
      participants who withdraw from the study early will be followed up for at least 28 days (±3
      days) after administration of the study drug unless participant consent is withdrawn.

      Safety Oversight :The study will be subject to oversight by an SMC comprised of the Principal
      Investigator (PI), local MM, and Sponsor medical representative as core members.

      The SMC will convene for each SAD dosing cohort to determine if dose escalation may proceed
      based on review of cumulative data. This will include, at a minimum, review of 28 days of
      post-treatment safety data (i.e., safety data up to and including the Day 29 visit) and all
      available PK data from the ongoing cohort as well as the accumulated data from all previous
      cohorts (where applicable). Where a participant is withdrawn from the study before Day 29,
      all available safety and PK data up to the time of withdrawal will be reviewed by the SMC.
      Data from participants receiving placebo and active treatment will be considered in the dose
      escalation discussion. The dose escalation decision will be based upon the nature, severity
      and frequency of any safety and/or tolerability observations, and the safety data will
      include any AEs or SAEs, ECG and vital sign and safety laboratory changes, and physical
      findings.

      Dose escalation: The SMC may recommend escalation to the next dose, escalation to an
      intermediate dose (a dose lower than the next planned dose), continuation or delay in dosing,
      repetition or expansion of a cohort, de-escalation to a lower dose, or termination of the
      study. The SMC may also recommend additional SAD dose cohorts, or they may pause the study to
      conduct an expert review and to determine next steps. Dose escalation decisions may be
      delayed to allow collection of additional data if indicated (e.g., safety and/ or PK data).

      No intra-cohort dose escalation is permitted.
    

Intervention name(s): ALT-100; Normal Saline
Intervention type(s): Drug; Other
Intervention description(s): intravenous infusion of drug substance diluted in 0.9% normal sterile saline; intravenous infusion of placebo (0.9% normal sterile saline)
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: First in human, randomized, double-blind, placebo-controlled, multi-cohort healthy volunteer trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Respiratory Distress Syndrome