Alpha 1-Antitrypsin DeficiencyPhase 1NCT04174118
Study of DCR-A1AT in Healthy Adult Volunteers
A Phase 1 study testing belcesiran in people with Alpha 1-Antitrypsin Deficiency, run by Dicerna Pharmaceuticals, Inc., a Novo Nordisk company at 2 sites in 2 countries.
Trial summary
This is a research study to test an experimental study drug (belcesiran, also known as DCR-A1AT). This drug is being tested to see if it helps people with a rare condition known as Alpha-1 Antitrypsin Deficiency, or A1ATD. Prior to initiation of this study belcesiran had not yet been tested in humans. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Alpha 1-Antitrypsin Deficiency
- What is being tested?
- belcesiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 24 Oct 2019to 6 Mar 2023
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or Female aged 18 to 55 years, inclusive. Female participants must be either surgically sterile or postmenopausal. No women of childbearing potential are eligible for enrollment.
- Overtly Healthy, as determined by the investigator.
- Serum A1AT protein concentration >100 mg/dL
- Adequate forced expiratory volume in one second (FEV1) and adequate FEV1/forced vital capacity (FVC) ratio
- Non-smokers with a <2 pack-year history and smoking cessation for at least 6 months with a negative urinary cotinine test a screening
Who cannot join
- Presence of any condition or comorbidities that would interfere with study compliance or data interpretation or potentially affect participant safety
- Clinically significant abnormal laboratory tests
- Received an experimental drug within past 4 months
- Prior to use of RNAi drug or oligonucleotide-based therapy
- Known human immunodeficiency virus (HIV), hepatitis C virus (HCV), or Hepatitis B (HBV)
- Serum creatinine or estimated glomerular filtration rate (eGFR) outside normal reference ranges.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Phase 1 Single Ascending Dose, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered Belcesiran in Healthy Adult Volunteers
This is a research study to test an experimental study drug (belcesiran, also known as DCR-A1AT). This drug is being tested to see if it helps people with a rare condition known as Alpha-1 Antitrypsin Deficiency, or A1ATD. Prior to initiation of this study belcesiran had not yet been tested in humans. All study participants will be randomly assigned to either receive the study drug or a placebo. This will allow for the sponsor to compare the effects of the study drug with that of the placebo. A placebo looks like the study drug but does not contain any of the study drug.
The main purpose of the first part of the study is to evaluate the safety profile of the study drug in people who do not have A1ATD. This part of the study will also help find the dose of the study drug that has an acceptable safety profile for testing.
Read the detailed description
A1ATD- associated liver disease is a progressive Alpha-1 Antitrypsin-Deficiency Associated Liver Disease condition resulting in liver fibrosis, cirrhosis, and hepatocellular carcinoma. The lack of functional A1AT in individuals with PiZZ genotype, in conjunction with other precipitating factors, can lead to unchecked activity in neutrophil elastases in the alveoli; causing emphysema and chronic obstructive pulmonary disease (COPD). This loss-of-function mechanism can be addressed with intravenous augmentation therapy, which aims to substitute the missing A1AT by infusing alpha1 proteinase inhibitor (A1PI), purified from pooled human plasma.
While augmentation therapy can address the loss of A1AT in the lungs, no treatment exists for the associated liver disease.
Given the severity of the disease, with approximately 10% of affected patients developing liver cirrhosis and a subgroup of those patients in need of liver transplantation, and lack of an effective treatment that addresses the toxic hepatic "gain-of-function" mechanism, there is an urgent unmet medical need to develop a therapy that can help in this particular patient population.
- Conditions
- Alpha 1-Antitrypsin Deficiency
- Being tested
- belcesiran, Placebo
- 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.
belcesiranDrug
belcesiran will be administered subcutaneously (SC) at dose levels planned.
PlaceboDrug
Sterile normal saline (0.9% NaCL) matching volume of belcesiran doses will be administered subcutaneously (SC).
| Study group | Role | What they receive |
|---|---|---|
| belcesiran | Experimental | Healthy volunteers will be administered a single dose of belcesiran. Receives: Drug: belcesiran |
| Placebo | Placebo comparator | Healthy volunteers will be administered a single dose of matching placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
The incidence of adverse events (AE), serious adverse events (SAE), DLT, and AE leading to study drug discontinuation
Measured: approximately up to 2 months
Evaluating safety and tolerability through physical exams
The incidence of clinically significant physical examination (PE) findings
Measured: approximately up to 2 months
Changes in 12-lead electrocardiograms (ECG)
Absolute QTc > 500 msec and/or QTc change of > 60 msec from baseline will be evaluated
Measured: approximately up to 2 months
Secondary outcomes (11)
Urine pharmacokinetics (PK) of belcesiran
Maximum observed concentration (Cmax)
Measured: up to Day 3
Plasma pharmacokinetics (PK) of belcesiran
Maximum observed concentration (Cmax)
Measured: up to 57 days
Plasma pharmacokinetics (PK) of belcesiran
Area under the curve (AUC)
Measured: up to 57 days
Urine pharmacokinetics (PK) of belcesiran
Area under the curve (AUC)
Measured: up to Day 3
Urine pharmacokinetics (PK) of belcesiran
Minimum observed concentration (Cmin)
Measured: up to Day 3
Plasma pharmacokinetics (PK) of belcesiran
Minimum observed concentration (Cmin)
Measured: up to 57 days
Plasma pharmacokinetics (PK) of belcesiran
Time to maximum concentration (Tmax)
Measured: up to 57 days
Urine pharmacokinetics (PK) of belcesiran
Time to maximum concentration (Tmax)
Measured: up to Day 3
Urine pharmacokinetics (PK) of belcesiran
Terminal elimination half-life (t1/2)
Measured: up to Day 3
Plama pharmacokinetics (PK) of belcesiran
Terminal elimination half-life (t1/2)
Measured: up to 57 days
Change in protein concentration
Changes in A1AT protein concentrations
Measured: up to day 57
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2019
- Study start24 Oct 2019
- Primary completion6 Jul 2021
- Study completion6 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Thomas Bowman, MD, Study director, Dicerna Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04174118
- Sponsor's protocol ID
- DCR-A1AT-101
- Status last verified
- Sep 2024
- First submitted
- 6 Nov 2019
- Last updated
- 6 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Remih K, Amzou S, Strnad P. Alpha1-antitrypsin deficiency: New therapies on the horizon. Curr Opin Pharmacol. 2021 Aug;59:149-156. doi: 10.1016/j.coph.2021.06.001. Epub 2021 Jul 10.
PubMed 34256305
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Single Ascending Dose, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered Belcesiran in Healthy Adult Volunteers
- ClinicalTrials.gov ID
- NCT04174118
- Acronym / sponsor ID
- DCR-A1AT-101
- Conditions
- Alpha 1-Antitrypsin Deficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Dicerna Pharmaceuticals, Inc., a Novo Nordisk companyIndustry (pharma, biotech, devices)
- Study start
- 24 Oct 2019 (actual)
- Primary completion
- 6 Jul 2021 (actual)
- Study completion
- 6 Mar 2023 (actual)
- First posted
- 22 Nov 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 a research study to test an experimental study drug (belcesiran, also known as DCR-A1AT). This drug is being tested to see if it helps people with a rare condition known as Alpha-1 Antitrypsin Deficiency, or A1ATD. Prior to initiation of this study belcesiran had not yet been tested in humans. All study participants will be randomly assigned to either receive the study drug or a placebo. This will allow for the sponsor to compare the effects of the study drug with that of the placebo. A placebo looks like the study drug but does not contain any of the study drug.
The main purpose of the first part of the study is to evaluate the safety profile of the study drug in people who do not have A1ATD. This part of the study will also help find the dose of the study drug that has an acceptable safety profile for testing.
Detailed description
A1ATD- associated liver disease is a progressive Alpha-1 Antitrypsin-Deficiency Associated Liver Disease condition resulting in liver fibrosis, cirrhosis, and hepatocellular carcinoma. The lack of functional A1AT in individuals with PiZZ genotype, in conjunction with other precipitating factors, can lead to unchecked activity in neutrophil elastases in the alveoli; causing emphysema and chronic obstructive pulmonary disease (COPD). This loss-of-function mechanism can be addressed with intravenous augmentation therapy, which aims to substitute the missing A1AT by infusing alpha1 proteinase inhibitor (A1PI), purified from pooled human plasma.
While augmentation therapy can address the loss of A1AT in the lungs, no treatment exists for the associated liver disease.
Given the severity of the disease, with approximately 10% of affected patients developing liver cirrhosis and a subgroup of those patients in need of liver transplantation, and lack of an effective treatment that addresses the toxic hepatic "gain-of-function" mechanism, there is an urgent unmet medical need to develop a therapy that can help in this particular patient population.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| belcesiran | Experimental | Drug: belcesiranHealthy volunteers will be administered a single dose of belcesiran. |
| Placebo | Placebo comparator | Drug: PlaceboHealthy volunteers will be administered a single dose of matching placebo. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Male or Female aged 18 to 55 years, inclusive. Female participants must be either surgically sterile or postmenopausal. No women of childbearing potential are eligible for enrollment.
- Overtly Healthy, as determined by the investigator.
- Serum A1AT protein concentration >100 mg/dL
- Adequate forced expiratory volume in one second (FEV1) and adequate FEV1/forced vital capacity (FVC) ratio
- Non-smokers with a <2 pack-year history and smoking cessation for at least 6 months with a negative urinary cotinine test a screening
Key exclusion criteria (6 listed)
- Presence of any condition or comorbidities that would interfere with study compliance or data interpretation or potentially affect participant safety
- Clinically significant abnormal laboratory tests
- Received an experimental drug within past 4 months
- Prior to use of RNAi drug or oligonucleotide-based therapy
- Known human immunodeficiency virus (HIV), hepatitis C virus (HCV), or Hepatitis B (HBV)
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 |
|---|---|---|
| belcesiranbelcesiran will be administered subcutaneously (SC) at dose levels planned. | Drug | belcesiran |
| PlaceboSterile normal saline (0.9% NaCL) matching volume of belcesiran doses will be administered subcutaneously (SC). | Drug | Placebo |
Primary outcome
Safety and tolerability
Time frame: approximately up to 2 months
The incidence of adverse events (AE), serious adverse events (SAE), DLT, and AE leading to study drug discontinuation
Evaluating safety and tolerability through physical exams
Time frame: approximately up to 2 months
The incidence of clinically significant physical examination (PE) findings
Changes in 12-lead electrocardiograms (ECG)
Time frame: approximately up to 2 months
Absolute QTc > 500 msec and/or QTc change of > 60 msec from baseline will be evaluated
11 secondary outcomes
Urine pharmacokinetics (PK) of belcesiran
Time frame: up to Day 3
Plasma pharmacokinetics (PK) of belcesiran
Time frame: up to 57 days
Plasma pharmacokinetics (PK) of belcesiran
Time frame: up to 57 days
Urine pharmacokinetics (PK) of belcesiran
Time frame: up to Day 3
Urine pharmacokinetics (PK) of belcesiran
Time frame: up to Day 3
Plasma pharmacokinetics (PK) of belcesiran
Time frame: up to 57 days
Plasma pharmacokinetics (PK) of belcesiran
Time frame: up to 57 days
Urine pharmacokinetics (PK) of belcesiran
Time frame: up to Day 3
Urine pharmacokinetics (PK) of belcesiran
Time frame: up to Day 3
Plama pharmacokinetics (PK) of belcesiran
Time frame: up to 57 days
Change in protein concentration
Time frame: up to day 57
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 6 Nov 2024.
- Derived from this study: PubMed 34256305Remih K, Amzou S, Strnad P. Alpha1-antitrypsin deficiency: New therapies on the horizon. Curr Opin Pharmacol. 2021 Aug;59:149-156. doi: 10.1016/j.coph.2021.06.001. Epub 2021 Jul 10.
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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.
Thomas Bowman, MD study director
Dicerna Pharmaceuticals
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing belcesiran in people with Alpha 1-Antitrypsin Deficiency, run by Dicerna Pharmaceuticals, Inc., a Novo Nordisk company at 2 sites in 2 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 5 inclusion and 6 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 6 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in New Zealand, Sweden. 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. Some participants in this study may receive a placebo. 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?
Safety and tolerability (time frame: approximately up to 2 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04174118, which also lists 1 linked publication.
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 6 Nov 2024.