Clinical trial NCT03815396: Phase 1 Study to Assess the Safety, PK and PD of INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency
Official title: An Open-Label, Multicenter, Phase 1 Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Intravenous Doses of Inhibrx rhAAT-Fc (INBRX-101) in Adults With Alpha-1 Antitrypsin Deficiency (AATD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alpha-1 Antitrypsin Deficiency
AATD
Keywords: Alpha-1 antitrypsin deficiency
AATD
alpha-1 disease
AAT
Lead sponsor: Inhibrx Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2019-01-24
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is an open-label, 2-part, dose-escalating, Phase 1 study of INBRX-101 (rhAAT-Fc). Part 1 will consist of single ascending dose (SAD) administration of INBRX-101 and Part 2 will consist of multiple ascending dose (MAD) administrations of INBRX-101. The planned dosing schedule is IV every 3 to 4 weeks.


Eligibility criteria: Inclusion Criteria:

* Documented alpha-1 antitrypsin (AAT) serum concentration \<11 μM.
* Diagnosis of alpha-1 antitrypsin deficiency (AATD) with any allelic combination with exception of the null/null genotype.
* For subjects in Part 2 80 and 120 mg/kg cohorts ONLY: post-bronchodilator FEV1 of at least 40% of predicted normal value.
* For subjects in Part 2 80 and 120 mg/kg cohorts ONLY: subjects eligible for bronchoscopy per judgment of investigator.
* Nonsmoker for at least 6 months prior to study and must remain nonsmoking for the entire study duration.
* Adequate hepatic and renal function as defined per protocol.
* Willing to undergo current augmentation therapy washout (if applicable) and refrain from initiating augmentation therapy, other investigational drug trials for AATD, therapy with IV immunoglobulins or monoclonal antibodies during the entire study, including follow-up.

Exclusion Criteria:

* Known or suspected allergy to components of INBRX-101 (AAT or human IgG) or pdAAT.
* Participation in any investigational drug trial within 30 days prior to this trial, or subjects receiving IV immunoglobulins or monoclonal antibodies within 30 days prior to this trial.
* History of and/or on the waiting list for lung or liver transplant, lobectomy, or lung volume reduction surgery.
* Acute respiratory tract infection or COPD exacerbation that required antibiotic treatment and/or increase in systemic steroid dosage within the 4 weeks prior to screening. Subjects are permitted to continue to receive steroids if the investigator judges the subject to have a history of stable dosing.
* Subjects with ongoing or history of unstable cor pulmonale.
* Infection with hepatitis A, B, or C or human immunodeficiency virus (HIV).
* Active autoimmune disease or documented history of autoimmune disease that 1) required systemic steroids or immune-suppressive medications and 2) tested positive for auto-antibodies. Exception: Endocrinopathies managed with hormone replacement therapy (HRT).
* Current substance and/or alcohol abuse with protocol defined exceptions.
* Current narcotics abuse with protocol defined exceptions.

Primary outcomes:
measure: Frequency of adverse events of INBRX-101
timeFrame: Up to 7 months
measure: Severity of adverse events of INBRX-101
timeFrame: Up to 7 months
Secondary outcomes:
measure: Area under the serum concentration time curve (AUC) of INBRX-101
timeFrame: Up to 7 months
measure: Maximum observed serum concentration (Cmax) of INBRX-101
timeFrame: Up to 7 months
measure: Trough observed serum concentration (Ctrough) of INBRX-101
timeFrame: Up to 7 months
measure: Time to Cmax (Tmax) of INBRX-101
timeFrame: Up to 7 months
measure: Half-life (T1/2) of INBRX-101
timeFrame: Up to 7 months
measure: Immunogenicity of INBRX-101
timeFrame: Up to 7 months
measure: Distribution of INBRX-101 in Bronchoalveolar Lavage Fluid (BALF)
timeFrame: Up to 7 months
measure: Functional concentration of INBRX-101 in serum and BALF
timeFrame: Up to 7 months
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis School of Medicine
state: California
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Hannibal
country: United States
facility: Hannibal Clinic
state: Missouri
city: Auckland
country: New Zealand
facility: The New Zealand Respiratory and Sleep Institute
city: Christchurch
country: New Zealand
facility: Christchurch Clinical Studies Trust Ltd
city: Hamilton
country: New Zealand
facility: Waikato Respiratory and Gastro Research Unit
city: Cambridge
country: United Kingdom
facility: University of Cambridge
state: East Of England
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham NHS Foundation Trust
state: West Midlands
Study officials:
affiliation: Inhibrx Biosciences, Inc
name: Vasily Andrianov, MD
role: STUDY_DIRECTOR
References: