First in Human Study in Healthy Volunteers Followed With Dosing in Participants With Lung or Liver Fibrosis

Study Overview
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Brief Summary
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First in Human single ascending dose followed by multiple ascending doses in healthy volunteers.

Official Title
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A Phase Ia/Ib, Randomized, Double Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BLD-2660 in Healthy Volunteers and Patients With Lung Fibrosis or Liver Fibrosis

Conditions
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Fibrosis

Intervention / Treatment
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* Drug: BLD-2660


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide written informed consent Agree to no smoking or alcohol or illegal substance 48 hours prior to dosing Have a negative urine drug screen/alcohol breath test on admission to clinic Agree to use highly effective, double barrier contraception (both male and female partners) during the study and for 30 days following completion of dosing Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1 Normal BMI except liver fibrosis participants (BMI 18 to ≤35 kg/m2) Be in general good health Clinical laboratory values within normal range Lung fibrosis participants-a diagnosis of lung fibrosis, Liver fibrosis participants-a diagnosis of liver fibrosis; some abnormal laboratory values will be acceptable for the following; platelet count, albumin, serum creatinine and neutrophil-leukocyte ration Exclusion Criteria: Presence of any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the subject will complete the study per protocol History or presence of alcoholism or drug abuse within the 2 years prior to the first study drug administration, and unwillingness to be totally abstinent during the dosing period Blood donation or significant blood loss within 60 days prior to the first study drug administration Plasma donation within 7 days prior to the first study drug administration Administration of investigational product (IP) in another trial within 30 days prior to the first study drug administration, or five half-lives, whichever is longer Females who are pregnant or lactating Surgery within the past 3 months prior to the first study drug administration determined by the PI to be clinically relevant Failure to satisfy the PI of fitness to participate for any other reason Active infection or history of recurrent infections Active malignancy and history of malignancy in the past 5 years, with the exception of completely excised basal cell carcinoma or low grade cervical intraepithelial neoplasia Chronic obstructive pulmonary disease Antibiotic treatment within 3 months Chronic medical condition

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cohort 1a - starting dose<br>Single oral dose of BLD-2660 or placebo capsule administered to healthy volunteers | Drug: BLD-2660<br>* Randomized to active product or placebo<br>* Other names: Placebo;|
| Placebo Comparator: cohort 1b- first SAD escalation<br>Single oral dose of BLD-2660 or placebo capsule(s) administered to healthy volunteers (1st dose escalation) | Drug: BLD-2660<br>* Randomized to active product or placebo<br>* Other names: Placebo;|
| Placebo Comparator: cohort 1c-2nd SAD escalation<br>Single oral dose of BLD-2660 or placebo capsule(s) administered to healthy volunteers (2nd dose escalation) in fasting state, followed by washout period and then single oral dose of BLD-2660 or placebo administered to healthy volunteers in fed state. | Drug: BLD-2660<br>* Randomized to active product or placebo<br>* Other names: Placebo;|
| Placebo Comparator: cohort 1d-3rd SAD escalation<br>Single oral dose of BLD-2660 or placebo capsules(s) administered to healthy volunteers (3rd dose escalation) | Drug: BLD-2660<br>* Randomized to active product or placebo<br>* Other names: Placebo;|
| Placebo Comparator: cohort 1e-4th SAD escalation<br>Single oral dose of BLD-2660 or placebo capsule(s) administered to healthy volunteers (final dose escalation if assessed as safe). | Drug: BLD-2660<br>* Randomized to active product or placebo<br>* Other names: Placebo;|
| Placebo Comparator: cohort 2a-1st MAD cohort<br>Multiple oral doses of BLD-2660 or placebo capsule(s) administered to healthy volunteers | Drug: BLD-2660<br>* Randomized to active product or placebo<br>* Other names: Placebo;|
| Placebo Comparator: cohort 2b-2nd MAD escalation<br>Multiple oral doses of BLD-2660 or placebo capsule(s) administered to healthy volunteers. | Drug: BLD-2660<br>* Randomized to active product or placebo<br>* Other names: Placebo;|
| Placebo Comparator: cohort 2c-3rd MAD escalation<br>Multiple oral doses of BLD-2660 or placebo capsule(s) administered to healthy volunteers. | Drug: BLD-2660<br>* Randomized to active product or placebo<br>* Other names: Placebo;|
| Placebo Comparator: cohort 2d-4th MAD escalation<br>Multiple oral doses of BLD-2660 or placebo capsule(s) administered to healthy volunteers. | Drug: BLD-2660<br>* Randomized to active product or placebo<br>* Other names: Placebo;|
| Placebo Comparator: cohort 2e-5th MAD escalation<br>Multiple oral doses of BLD-2660 or placebo capsule(s) administered to healthy volunteers. | Drug: BLD-2660<br>* Randomized to active product or placebo<br>* Other names: Placebo;|
| Placebo Comparator: cohort 2F-6th MAD escalation<br>Multiple oral doses of BLD-2660 or placebo capsule(s) administered to healthy volunteers. | Drug: BLD-2660<br>* Randomized to active product or placebo<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) | AEs will be assessed by determining the incidence, severity, and dose relationship of adverse events | 2 weeks | 
| Any observed changes in clinical safety laboratory results | Assessed by reviewing any observed changes in CBC, serum chemistry or urinalysis from baseline by dose. Results in subjects dosed with BLD-2660 treatment will be compared to those dosed with placebo. | 2 weeks | 
| Any observed changes in physical examinations | Assessed by reviewing any observed changes in physical examinations from baseline by dose. Results in subjects dosed with BLD-2660 will be compared to those dosed with placebo. | 2 weeks | 
| Any observed changes in vital signs | Assessed by reviewing any observed changes in vital signs from baseline by dose. Results in subjects dosed with BLD-2660 will be compared to those dosed with placebo. | 2 weeks | 
| Any observed changes in ECG | Assessed by reviewing any observed changes in ECG from baseline by dose. Results in subjects dosed with BLD-2660 will be compared to those dosed with placebo. | 2 weeks |