An extension study to evaluate Safety and Pharmacodynamics of Belcesiran in patients with PiZZ Alpha-1 Antitrypsin Deficiency.
- Conditions
- PiZZAlpha-1 Antitrypsin Deficiency Associated Liver DiseaseMedDRA version: 23.1Level: LLTClassification code 10001806Term: Alpha-1 anti-trypsin deficiencySystem Organ Class: 100000004850Therapeutic area: Body processes [G] - Genetic Phenomena [G05]
- Registration Number
- EUCTR2021-005217-14-ES
- Lead Sponsor
- Dicerna Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 54
Age
1. Must be 18 to 75 years of age inclusive, at the time of signing the Informed Consent.
Type of Participant and Disease Characteristics – Cohort A
2. Documented diagnosis of PiZZ-type AATD
3. Completed the assigned 24- or 48-week treatment period in DCR-A1AT-201
a. All test results (except for liver biopsy results) from DCR-A1AT-201 must have been received prior to Day 1
b. DCR-A1AT-201 EOT liver biopsy must have been performed prior to Day 1
4. Pre- and post-bronchodilator FEV1 > 60% of predicted at EOT Visit in DCR-A1AT-201
5. Post-bronchodilator DLCO = 50% of predicted at EOT Visit in DCR-A1AT-201
6. Estimated glomerular filtration rate = 60 mL/min/1.73 m2 at EOT Visit in DCR-A1AT-201
7. No more than 56 days may have elapsed from EOT Visit in DCR-A1AT-201 to first dose (Day 1) in DCR-A1AT-202
Type of Participant and Disease Characteristics – Cohort B
8. Documented diagnosis of PiZZ-type AATD
9. Offered the opportunity to enter DCR-A1AT-202 after completing the assigned treatment period in DCR-A1AT-201 but declined to participate at that time
10. Completed 48 weeks of CFU in DCR-A1AT-201
11. Serum AAT protein concentration did not return to = 80% of baseline at EOS Visit in DCR-A1AT-201
12. No more than 28 days may have elapsed from EOS in DCR-A1AT-201 to Day 1 in DCR-A1AT-202
Sex
13. Male participants: A male participant with a partner of childbearing potential must agree to use contraception, as detailed in Section 10.4, during the treatment period (Cohort A only) and for at least 12 weeks after the last dose of study intervention and refrain from donating sperm during this period. Contraceptive use should be regulations regarding the methods of contraception for those participating in clinical studies.
Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and not a WOCBP, as defined in Section 10.4.1 of the Protocol
Informed Consent
14. Capable of giving signed informed consent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the ICF and in this Protocol. consistent with local
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 49
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5
Prior/Concomitant Therapy
1. Routine use of acetaminophen/paracetamol during the Treatment Period (Cohort A only) NOTE: Occasional use of up to 1000 mg/day is acceptable
2. Use of systemically acting steroids throughout the Treatment Period (Cohort A only). Occasional use is acceptable if needed for participant safety, e.g., in the case of an exacerbation of underlying pre-existing conditions.
3. Routine use of NSAIDs during the Treatment Period or use within 3 days of dosing (Cohort A only)
Diagnostic Assessments (Cohort A only)
Diagnostic assessments from the EOT Visit in DCR-A1AT-201 may be used for screening/determination of eligibility. Should more than 28 days elapse between the DCR-A1AT-201 EOT visit and Day 1 of DCR-A1AT-202, all diagnostic assessments must be repeated.
4. AST and ALT > 5 × ULN
5. ALP 2 × ULN
6. Serum AFP > 100 ng/mL
NOTE: If AFP at screening is above the ULN but < 100 ng/mL, the participant is still eligible if an appropriate hepatic imaging study reveals no lesions
7. HbA1c > 8%
NOTE: HbA1c is not assessed at the DCR-A1AT-201 EOT Visit. Testing is only required if more than 28 days elapse between the DCR-A1AT-201 EOT visit and Day 1 of DCR-A1AT-202.
8. Fasting triglycerides > 400 mg/dL or total cholesterol > 400 mg/dL
9. Platelets < 50,000/mm³
10. White blood cells < 2000/mm³
11. Neutrophils < 1000/mm³
12. INR > 1.6 × ULN
13. Blood pressure parameters, defined as Systolic BP > 150 mmHg and diastolic BP > 90 mmHg after 5 minutes rest in the sitting position at Screening.
NOTE: Repeat measures are allowed.
14. Positive SARS-CoV-2 virus test at Screening, via a confirmatory test, for example RT-PCR or Nucleic Acid Amplification Test (NAAT)
15. Any other safety laboratory test result considered clinically significant and unacceptable by the Investigator
Other Exclusions
16. Inability or unwillingness to comply with the specified study procedures, including lifestyle considerations
17. Any condition that, in the opinion of the Investigator, would make the participant unsuitable for enrollment or could interfere with participation in or completion of the study
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the long-term safety of belcesiran in patients with AATLD;Secondary Objective: To further characterize the PD of belcesiran in patients with AATLD;Primary end point(s): The incidence and nature of treatment-emergent adverse events (TEAEs), and the change from baseline in PFTs, 12-lead ECGs, physical examination findings, vital signs, and clinical laboratory tests;Timepoint(s) of evaluation of this end point: Throughout the study
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Changes in serum AAT protein concentrations over time;Timepoint(s) of evaluation of this end point: Throughout the study