Phase 1 Study to Assess the Safety, PK and PD of INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency

• Register: ClinicalTrials.gov
• Last refreshed on: 19 September 2022
• Main ID: NCT03815396
• Date of registration: 21/01/2019
• Prospective Registration: Yes
• Primary sponsor: Inhibrx, Inc.
• Public title: Phase 1 Study to Assess the Safety, PK and PD of INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency rhAAT-Fc
• Scientific 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)
• Date of first enrolment: July 19, 2019
• Target sample size: 31
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03815396
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

New Zealand, United Kingdom, United States

Contacts

• Name: Vasily Andrianov, MD
• Affiliation: Inhibrx, Inc.

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

AATD

Alpha-1 Antitrypsin Deficiency

Intervention(s)

Drug: INBRX-101/rhAAT-Fc

Primary Outcome(s)

Frequency of adverse events of INBRX-101 [Time Frame: Up to 7 months]

Severity of adverse events of INBRX-101 [Time Frame: Up to 7 months]

Secondary Outcome(s)

Immunogenicity of INBRX-101 [Time Frame: Up to 7 months]

Time to Cmax (Tmax) of INBRX-101 [Time Frame: Up to 7 months]

Half-life (T1/2) of INBRX-101 [Time Frame: Up to 7 months]

Trough observed serum concentration (Ctrough) of INBRX-101 [Time Frame: Up to 7 months]

Maximum observed serum concentration (Cmax) of INBRX-101 [Time Frame: Up to 7 months]

Distribution of INBRX-101 in Bronchoalveolar Lavage Fluid (BALF) [Time Frame: Up to 7 months]

Functional concentration of INBRX-101 in serum and BALF [Time Frame: Up to 7 months]

Area under the serum concentration time curve (AUC) of INBRX-101 [Time Frame: Up to 7 months]

Secondary ID(s)

Ph1 INBRX-101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors