Alpha-1 Antitrypsin DeficiencyPhase 1rhAAT-FcNCT03815396
Phase 1 Study to Assess the Safety, PK and PD of INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency
A Phase 1 study testing INBRX-101/rhAAT-Fc in people with Alpha-1 Antitrypsin Deficiency and AATD, run by Inhibrx Biosciences, Inc at 10 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Alpha-1 Antitrypsin Deficiency, AATD
- What is being tested?
- INBRX-101/rhAAT-Fc
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 19 Jul 2019to 18 Aug 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 9Show fewer
- 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.
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
United States5 sites
University of Florida College of Medicine
Gainesville, Florida, 32611
Hannibal Clinic
Hannibal, Missouri, 63401
Indiana University
Indianapolis, Indiana, 46202
University of Miami
Miami, Florida, 33125
UC Davis School of Medicine
Sacramento, California, 95817
New Zealand3 sites
The New Zealand Respiratory and Sleep Institute
Auckland
Christchurch Clinical Studies Trust Ltd
Christchurch
Waikato Respiratory and Gastro Research Unit
Hamilton
United Kingdom2 sites
University Hospital Birmingham NHS Foundation Trust
Birmingham, West Midlands, B15 2GW
University of Cambridge
Cambridge, East of England, CB2 0QQ
About this study
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)
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.
- Conditions
- Alpha-1 Antitrypsin Deficiency, AATD
- Being tested
- INBRX-101/rhAAT-Fc
- Keywords
- Alpha-1 antitrypsin deficiency, AATD, alpha-1 disease, AAT
- Medical subject headings
- alpha 1-Antitrypsin Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INBRX-101/rhAAT-FcDrug
INBRX-101 is a recombinant human alpha-1 antitrypsin (AAT) Fc fusion protein (rhAAT-Fc).
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Single Ascending Dose | Experimental | INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD). Receives: Drug: INBRX-101/rhAAT-Fc |
| Part 2 Multiple Ascending Dose | Experimental | INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD). Receives: Drug: INBRX-101/rhAAT-Fc |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of adverse events of INBRX-101
Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
Measured: Up to 7 months
Severity of adverse events of INBRX-101
Severity of adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
Measured: Up to 7 months
Secondary outcomes (8)
Area under the serum concentration time curve (AUC) of INBRX-101
Area under the serum concentration time curve (AUC) of INBRX-101 will be determined.
Measured: Up to 7 months
Maximum observed serum concentration (Cmax) of INBRX-101
Maximum observed serum concentration (Cmax) of INBRX-101 will be determined.
Measured: Up to 7 months
Trough observed serum concentration (Ctrough) of INBRX-101
Trough observed serum concentration (Cmax) of INBRX-101 will be determined.
Measured: Up to 7 months
Time to Cmax (Tmax) of INBRX-101
Time to Cmax (Tmax) of INBRX-101 will be determined.
Measured: Up to 7 months
Half-life (T1/2) of INBRX-101
Half-life of INBRX-101 will be determined.
Measured: Up to 7 months
Immunogenicity of INBRX-101
Frequency and consequences of anti-drug antibodies (ADA) against INBRX-101 will be determined.
Measured: Up to 7 months
Distribution of INBRX-101 in Bronchoalveolar Lavage Fluid (BALF)
The concentration of INBRX-101 in bronchoalveolar lavage fluid (BALF) be determined.
Measured: Up to 7 months
Functional concentration of INBRX-101 in serum and BALF
The functional concentration of INBRX-101 in serum and BALF will be determined.
Measured: Up to 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2019
- Study start19 Jul 2019
- Primary completion18 Aug 2022
- Study completion18 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alpha-1 Antitrypsin DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inhibrx Biosciences, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Vasily Andrianov, MD, Study director, Inhibrx Biosciences, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03815396
- Sponsor's protocol ID
- Ph1 INBRX-101
- Acronym
- rhAAT-Fc
- Status last verified
- Sep 2022
- First submitted
- 21 Jan 2019
- Last updated
- 13 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03815396
- Acronym / sponsor ID
- rhAAT-Fc / Ph1 INBRX-101
- Conditions
- Alpha-1 Antitrypsin Deficiency, AATD
- Keywords
- Alpha-1 antitrypsin deficiency, AATD, alpha-1 disease, AAT
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Inhibrx Biosciences, IncIndustry (pharma, biotech, devices)
- Study start
- 19 Jul 2019 (actual)
- Primary completion
- 18 Aug 2022 (actual)
- Study completion
- 18 Aug 2022 (actual)
- First posted
- 24 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 Single Ascending Dose | Experimental | Drug: INBRX-101/rhAAT-FcINBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD). |
| Part 2 Multiple Ascending Dose | Experimental | Drug: INBRX-101/rhAAT-FcINBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INBRX-101/rhAAT-FcINBRX-101 is a recombinant human alpha-1 antitrypsin (AAT) Fc fusion protein (rhAAT-Fc). | Drug | Part 1 Single Ascending Dose, Part 2 Multiple Ascending Dose |
Primary outcome
Frequency of adverse events of INBRX-101
Time frame: Up to 7 months
Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
Severity of adverse events of INBRX-101
Time frame: Up to 7 months
Severity of adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
8 secondary outcomes
Area under the serum concentration time curve (AUC) of INBRX-101
Time frame: Up to 7 months
Maximum observed serum concentration (Cmax) of INBRX-101
Time frame: Up to 7 months
Trough observed serum concentration (Ctrough) 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
Immunogenicity 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vasily Andrianov, MD study director
Inhibrx Biosciences, Inc
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing INBRX-101/rhAAT-Fc in people with Alpha-1 Antitrypsin Deficiency and AATD, run by Inhibrx Biosciences, Inc at 10 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, New Zealand, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of adverse events of INBRX-101 (time frame: Up to 7 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2022.