Trial record 2 of 3 for:
ARO-AAT Injection | AAT liver disease
Safety, Tolerability and Pharmacodynamic Effect of ARO-AAT (SEQUOIA)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03945292 |
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Recruitment Status :
Active, not recruiting
First Posted : May 10, 2019
Last Update Posted : March 7, 2022
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Sponsor:
Arrowhead Pharmaceuticals
Information provided by (Responsible Party):
Arrowhead Pharmaceuticals
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Brief Summary:
The purpose of AROAAT2001 (SEQUOIA) is to evaluate the safety, efficacy and tolerability of multiple doses of the investigational product, ARO-AAT, administered subcutaneously to participants with alpha-1 antitrypsin deficiency (AATD).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Alpha 1-Antitrypsin Deficiency | Drug: ARO-AAT Injection Other: Placebo | Phase 2 |
Participants will be enrolled to receive multiple subcutaneous injections of ARO-AAT or placebo. Eligible participants will require a pre-dose biopsy completed as part of the study within the screening window. However, any participant with a biopsy result within 1 year of screening showing no fibrosis does not require a pre-dose biopsy. Only participants who have liver fibrosis will undergo a post-dose biopsy and may continue treatment in an open-label extension.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 40 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Placebo-Controlled, Multi-dose, Phase 2 Study to Determine the Safety, Tolerability and Pharmacodynamic Effect of ARO-AAT in Patients With Alpha-1 Antitrypsin Deficiency (AATD) [SEQUOIA] |
| Actual Study Start Date : | August 7, 2019 |
| Estimated Primary Completion Date : | July 13, 2022 |
| Estimated Study Completion Date : | July 13, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Alpha-1 antitrypsin deficiency
MedlinePlus related topics:
Alpha-1 Antitrypsin Deficiency
| Arm | Intervention/treatment |
|---|---|
|
Experimental: ARO-AAT
Participants with no fibrosis: Administered on Day 1 and Week 4 Participants with fibrosis: Administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 15 total doses. |
Drug: ARO-AAT Injection
solution for subcutaneous (sc) injection |
|
Placebo Comparator: Placebo
Participants with no fibrosis: Administered on Day 1 and Week 4 Participants with fibrosis: Administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 15 total doses. |
Other: Placebo
sterile normal saline (0.9% NaCl), calculated to match active comparator, for sc injection |
Primary Outcome Measures :
- Percentage Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) [ Time Frame: Baseline, Week 16 (+/- 2 weeks) ]
Secondary Outcome Measures :
- Absolute Change from Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants with Fibrosis [ Time Frame: Baseline, Week 48 (+/- 2 Weeks), or Week 72 (+/- 4 Weeks), or Week 96 (+/- 4 Weeks) ]
- Percent Change from Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants with Fibrosis [ Time Frame: Baseline, Week 48 (+/- 2 Weeks), or Week 72 (+/- 4 Weeks), or Week 96 (+/- 4 Weeks) ]
- Absolute Change from Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants with Fibrosis [ Time Frame: Baseline, Week 48 (+/- 2 Weeks), or Week 72 (+/- 4 Weeks), or Week 96 (+/- 4 Weeks) ]
- Percent Change from Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants with Fibrosis [ Time Frame: Baseline, Week 48 (+/- 2 Weeks), or Week 72 (+/- 4 Weeks), or Week 96 (+/- 4 Weeks) ]
- Absolute Change from Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants with Fibrosis [ Time Frame: Baseline, Week 48 (+/- 2 Weeks), or Week 72 (+/- 4 Weeks), or Week 96 (+/- 4 Weeks) ]
- Percent Change from Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants with Fibrosis [ Time Frame: Baseline, Week 48 (+/- 2 Weeks), or Week 72 (+/- 4 Weeks), or Week 96 (+/- 4 Weeks) ]
- Number of Participants With Adverse Events (AEs) at Week 16 and over time through End of Study (EOS) [ Time Frame: Week 16 (+/- 2 weeks) through Week 64 (+/- 2 weeks) (participants without fibrosis) or Week 16 (+/- 2 weeks) through Week 172 (participants with fibrosis) ]
- Absolute Change from Baseline in Liver Function Tests: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Gamma-Glutamyl Transferase (GGT) at Week 16 and over time through EOS [ Time Frame: Baseline, Week 16 (+/- 2 Weeks), Participants Without Fibrosis: through Week 64 (+/- 2 Weeks), Participants With Fibrosis: through Week 172 ]
- Percent Change from Baseline in Liver Function Tests: ALT, AST, ALP, GGT at Week 16 and over time through EOS [ Time Frame: Baseline, Week 16 (+/- 2 Weeks), Participants Without Fibrosis: through Week 64 (+/- 2 Weeks), Participants With Fibrosis: through Week 172 ]
- Absolute Change from Baseline in Liver Function Tests: Total Bilirubin, Direct Bilirubin at Week 16 and over time through EOS [ Time Frame: Baseline, Week 16 (+/- 2 Weeks), Participants Without Fibrosis: through Week 64 (+/- 2 Weeks), Participants With Fibrosis: through Week 172 ]
- Percent Change from Baseline in Liver Function Tests: Total Bilirubin, Direct Bilirubin at Week 16 and over time through EOS [ Time Frame: Baseline, Week 16 (+/- 2 Weeks), Participants Without Fibrosis: through Week 64 (+/- 2 Weeks), Participants With Fibrosis: through Week 172 ]
- Absolute Change from Baseline in Liver Function Tests: International Normalized Ratio (INR) at Week 16 and over time through EOS [ Time Frame: Baseline, Week 16 (+/- 2 Weeks), Participants Without Fibrosis: through Week 64 (+/- 2 Weeks), Participants With Fibrosis: through Week 172 ]
- Percent Change from Baseline in Liver Function Tests: INR at Week 16 and over time through EOS [ Time Frame: Baseline, Week 16 (+/- 2 Weeks), Participants Without Fibrosis: through Week 64 (+/- 2 Weeks), Participants With Fibrosis: through Week 172 ]
- Absolute Change in Serum Z-AAT Over Time through EOS [ Time Frame: Baseline, Participants Without Fibrosis: through Week 64 (+/- 2 Weeks), Participants With Fibrosis: through Week 172 ]
- Percent Change in Serum Z-AAT Over Time through EOS [ Time Frame: Baseline, Participants Without Fibrosis: through Week 64 (+/- 2 Weeks), Participants With Fibrosis: through Week 172 ]
- Pharmacokinetics (PK) of ARO-AAT: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Participants Without Fibrosis: Pre-dose, 1 hour, 2 hour & 24 or 48 hours post-dose on Day 1 (+/- 1 Day); Participants with Fibrosis: Pre-dose, 1 hour, 2 hours & 24 or 48 hours post-dose on Days 1 and 113 (+/- 1 Day) ]
- PK of ARO-AAT: Time to Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Participants Without Fibrosis: Pre-dose, 1 hour, 2 hour & 24 or 48 hours post-dose on Day 1 (+/- 1 Day); Participants with Fibrosis: Pre-dose, 1 hour, 2 hours & 24 or 48 hours post-dose on Days 1 and 113 (+/- 1 Day) ]
- PK of ARO-AAT: Terminal Elimination Half-Life (t1/2) [ Time Frame: Participants Without Fibrosis: Pre-dose, 1 hour, 2 hours & 24 or 48 hours post-dose on Day 1 (+/- 1 Day); Participants with Fibrosis: Pre-dose, 1 hour, 2 hours & 24 or 48 hours post-dose on Days 1 and 113 (+/- 1 Day) ]
- PK of ARO-AAT: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Time Point with a Quantifiable Concentration (AUC0-t) [ Time Frame: Participants Without Fibrosis: Pre-dose, 1 hour, 2 hour & 24 or 48 hours post-dose on Day 1 (+/- 1 Day); Participants with Fibrosis: Pre-dose, 1 hour, 2 hours & 24 or 48 hours post-dose on Days 1 and 113 (+/- 1 Day) ]
- PK of ARO-AAT: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUCinf) [ Time Frame: Participants Without Fibrosis: Pre-dose, 1 hour, 2 hour & 24 or 48 hours post-dose on Day 1 (+/- 1 Day); Participants with Fibrosis: Pre-dose, 1 hour, 2 hours & 24 or 48 hours post-dose on Days 1 and 113 (+/- 1 Day) ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Diagnosis of AATD
- Liver biopsy at Screening indicating liver fibrosis (score less than F4); a patient with no fibrosis may participate based on a previous biopsy conducted within one year
- Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception
- Willing to provide written informed consent and to comply with study requirements
- Non-smoker for at least 1 year
- No abnormal finding of clinical relevance at Screening
Exclusion Criteria:
- Clinically significant health concerns other than AATD
- Previous diagnosis or diagnosis at Screening of definitive liver cirrhosis
- Previous lung or liver transplant due to AATD
- Regular use of alcohol within one month prior to Screening
- Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study involving therapeutic intervention
- Use of illicit drugs within 1 year prior to Screening
NOTE: additional inclusion/exclusion criteria may apply, per protocol
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03945292
Locations
Show 22 study locations
Sponsors and Collaborators
Arrowhead Pharmaceuticals
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Arrowhead Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT03945292 |
| Other Study ID Numbers: |
AROAAT2001 2018-003385-14 ( EudraCT Number ) |
| First Posted: | May 10, 2019 Key Record Dates |
| Last Update Posted: | March 7, 2022 |
| Last Verified: | March 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
Additional relevant MeSH terms:
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Alpha 1-Antitrypsin Deficiency Liver Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases |
Genetic Diseases, Inborn Subcutaneous Emphysema Emphysema Pathologic Processes |