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