Trial Outcomes & Findings for Patisiran in Patients With Hereditary Transthyretin-mediated Amyloidosis (hATTR Amyloidosis) Disease Progression Post-Liver Transplant (NCT NCT03862807)
NCT ID: NCT03862807
Last Updated: 2024-04-22
Results Overview
Serum TTR was assessed using enzyme linked immunosorbent assay (ELISA). The average of the percentage reduction in serum TTR observed at Month 6 and at Month 12 is first calculated for each patient and then the median (95% CI) of these averaged values is summarized for the Safety Analysis Set.
COMPLETED
PHASE3
24 participants
Baseline, Months 6 and 12
2024-04-22
Participant Flow
Participants with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) with disease progression post-orthotopic liver transplant were enrolled at nine sites in France, Germany, Italy, Portugal, Spain, Sweden and the United Kingdom.
Participant milestones
| Measure |
Patisiran
Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.
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|---|---|
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Overall Study
STARTED
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24
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Overall Study
Treated
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23
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Overall Study
Completed Treatment
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22
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Overall Study
COMPLETED
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23
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Overall Study
NOT COMPLETED
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1
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Reasons for withdrawal
| Measure |
Patisiran
Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.
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|---|---|
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Overall Study
Not Treated Due to Eligibility Criteria Failure
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1
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Baseline Characteristics
Patisiran in Patients With Hereditary Transthyretin-mediated Amyloidosis (hATTR Amyloidosis) Disease Progression Post-Liver Transplant
Baseline characteristics by cohort
| Measure |
Patisiran
n=23 Participants
Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.
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|---|---|
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Age, Continuous
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58.1 years
STANDARD_DEVIATION 9.9 • n=39 Participants
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Sex: Female, Male
Female
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10 Participants
n=39 Participants
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Sex: Female, Male
Male
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13 Participants
n=39 Participants
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Race/Ethnicity, Customized
White
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22 Participants
n=39 Participants
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Race/Ethnicity, Customized
Asian
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1 Participants
n=39 Participants
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Race/Ethnicity, Customized
Not Hispanic or Latino
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23 Participants
n=39 Participants
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Serum Transthyretin (TTR)
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192.140 mg/L
n=39 Participants
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PRIMARY outcome
Timeframe: Baseline, Months 6 and 12Population: Safety Analysis Set: All participants who received any amount of patisiran.
Serum TTR was assessed using enzyme linked immunosorbent assay (ELISA). The average of the percentage reduction in serum TTR observed at Month 6 and at Month 12 is first calculated for each patient and then the median (95% CI) of these averaged values is summarized for the Safety Analysis Set.
Outcome measures
| Measure |
Patisiran
n=22 Participants
Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.
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|---|---|
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Average of Month 6 and Month 12 Percentage Reduction From Baseline in Serum Transthyretin (TTR)
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91.0 percent reduction
Interval 86.1 to 92.3
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SECONDARY outcome
Timeframe: Baseline, Month 12Population: Participants from the Per Protocol (PP) Analysis Set, all participants in the Safety Analysis Set who missed ≤2 doses of patisiran due to the COVID-19 pandemic during the study, with NIS data available at Month 12.
The NIS is a composite neurologic impairment score that assesses motor weakness (NIS-W), sensation (NIS-S) and reflexes (NIS-R) by physical exam. The minimum and maximum values are 0 and 244, respectively. A higher score indicates a worse outcome.
Outcome measures
| Measure |
Patisiran
n=20 Participants
Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.
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|---|---|
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Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 12
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-3.7 score on a scale
Standard Error 2.7
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SECONDARY outcome
Timeframe: Baseline, Month 12Population: Per Protocol (PP) Analysis Set: All participants in the Safety Analysis Set who missed ≤2 doses of patisiran due to the COVID-19 pandemic during the study.
The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The minimum and maximum values are -4 and 136, respectively. A higher score indicates a worse outcome.
Outcome measures
| Measure |
Patisiran
n=21 Participants
Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.
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|---|---|
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Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Score at Month 12
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-6.5 score on a scale
Standard Error 4.9
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SECONDARY outcome
Timeframe: Baseline, Month 12Population: Per Protocol (PP) Analysis Set: All participants in the Safety Analysis Set who missed ≤2 doses of patisiran due to the COVID-19 pandemic during the study.
The R-ODS is comprised of a 24-item linearly weighted scale that specifically captures activity and social participation limitations. The minimum and maximum values are 0 and 48, respectively. A higher score indicates a better outcome.
Outcome measures
| Measure |
Patisiran
n=21 Participants
Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.
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|---|---|
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Change From Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 12
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-0.1 score on a scale
Standard Error 1.1
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SECONDARY outcome
Timeframe: Baseline, Month 12Population: Participants from the Per Protocol (PP) Analysis Set, all participants in the Safety Analysis Set who missed ≤2 doses of patisiran due to the COVID-19 pandemic during the study, with COMPASS-31 data available at Month 12.
The COMPASS-31 questionnaire is a measure of autonomic neuropathy symptoms. The questions evaluate 6 autonomic domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor). The minimum and maximum values are 0 and 100, respectively. A higher score indicates a worse outcome.
Outcome measures
| Measure |
Patisiran
n=20 Participants
Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.
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|---|---|
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Change From Baseline in the Composite Autonomic Symptom Score (COMPASS-31) at Month 12
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-5.0 score on a scale
Standard Error 2.6
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SECONDARY outcome
Timeframe: Baseline, Month 12Population: Per Protocol (PP) Analysis Set: All participants in the Safety Analysis Set who missed ≤2 doses of patisiran due to the COVID-19 pandemic during the study.
Nutritional status of participants was evaluated using the mBMI, calculated as BMI (kg/m\^2) multiplied by albumin (g/L). An increase from baseline in mBMI suggests improvement, and a decrease from baseline suggests worsening.
Outcome measures
| Measure |
Patisiran
n=21 Participants
Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.
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|---|---|
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Change From Baseline in the Modified Body Mass Index (mBMI) at Month 12
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4.4 (kg/m^2)*(g/L)
Standard Error 21.8
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SECONDARY outcome
Timeframe: From baseline to end of study at Month 13Population: Safety Analysis Set: All participants who received any amount of patisiran.
An AE is any untoward medical occurrence in a participant or clinical investigational patient administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Outcome measures
| Measure |
Patisiran
n=23 Participants
Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.
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Percentage of Participants With Adverse Events
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100 percentage of participants
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Adverse Events
Patisiran
Serious adverse events
| Measure |
Patisiran
n=23 participants at risk
Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.
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Cardiac disorders
Atrial thrombosis
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4.3%
1/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Cardiac disorders
Cardiac failure
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13.0%
3/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Hepatobiliary disorders
Cholangitis
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4.3%
1/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Immune system disorders
Infusion related reaction
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4.3%
1/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Infections and infestations
Pneumonia
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4.3%
1/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Infections and infestations
Urinary tract infection
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4.3%
1/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Injury, poisoning and procedural complications
Hip fracture
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4.3%
1/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Nervous system disorders
Syncope
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4.3%
1/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Renal and urinary disorders
Haematuria
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4.3%
1/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Renal and urinary disorders
Urinary retention
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4.3%
1/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Respiratory, thoracic and mediastinal disorders
Atelectasis
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4.3%
1/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Other adverse events
| Measure |
Patisiran
n=23 participants at risk
Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.
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|---|---|
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Ear and labyrinth disorders
Vertigo
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8.7%
2/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Gastrointestinal disorders
Abdominal pain
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8.7%
2/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Gastrointestinal disorders
Bile acid malabsorption
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8.7%
2/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Gastrointestinal disorders
Diarrhoea
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34.8%
8/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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General disorders
Asthenia
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8.7%
2/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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General disorders
Chest pain
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8.7%
2/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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General disorders
Fatigue
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13.0%
3/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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General disorders
Oedema peripheral
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21.7%
5/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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General disorders
Pyrexia
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13.0%
3/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Immune system disorders
Infusion related reaction
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26.1%
6/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Infections and infestations
Bronchitis
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8.7%
2/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Infections and infestations
Cystitis
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8.7%
2/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Infections and infestations
Urinary tract infection
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8.7%
2/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Injury, poisoning and procedural complications
Fall
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13.0%
3/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Injury, poisoning and procedural complications
Skin laceration
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8.7%
2/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Musculoskeletal and connective tissue disorders
Back pain
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21.7%
5/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Nervous system disorders
Headache
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13.0%
3/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Renal and urinary disorders
Oliguria
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8.7%
2/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Vascular disorders
Poor venous access
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8.7%
2/23 • From baseline to end of study at Month 13.
Safety Analysis Set: All participants who received any amount of patisiran.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee It is intended that after completion of the study, the data are to be submitted for publication in a scientific journal and/or for reporting at a scientific meeting. A separate publication by Institution or PI may not be submitted for publication until after this primary manuscript is published or following 12 months after completion of the study. A copy of any proposed publication based on this study, must be provided and confirmed received at the Sponsor at least 30 days before its submission.
- Publication restrictions are in place
Restriction type: OTHER