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Safety and Tolerability of Patisiran (ALN-TTR02) in Transthyretin (TTR) Amyloidosis

A Phase 2, Open-Label, Multi-Dose, Dose Escalation Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous Infusions of ALN-TTR02 in Patients With TTR Amyloidosis

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01617967
Enrollment
29
Registered
2012-06-13
Start date
2012-05-31
Completion date
2014-01-31
Last updated
2024-04-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

TTR-mediated Amyloidosis

Keywords

RNAi therapeutic

Brief summary

This was a multiple dose, dose escalation study designed to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of patisiran (ALN-TTR02) in participants with transthyretin (TTR) mediated amyloidosis (ATTR).

Interventions

DRUGPatisiran

Participants received a single dose of patisiran as an intravenous (IV) infusion on Day 0 and Day 28 (Q4W). Optional cohorts received an alternative dosing regimen (once every 3 weeks \[Q3W\]: Day 0 and Day 21) and an alternative premedication regimen.

Sponsors

Alnylam Pharmaceuticals
Lead SponsorINDUSTRY

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No

Inclusion criteria

* Body mass index must be between 17 kg/m\^2 and ≤ 33 kg/m\^2; * Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must use appropriate contraception; * Males agree to use appropriate contraception; * Diagnosis of TTR amyloidosis; * Adequate blood counts, liver and renal function; * Willing to give written informed consent and are willing to comply with the study requirements.

Exclusion criteria

* Known human immunodeficiency virus (HIV) positive status or known or suspected systemic bacterial, viral, parasitic, or fungal infection; * Received an investigational agent, other than tafamidis or diflunisal, within 30 days prior to first dose study drug administration; * Prior liver transplant; * Poor cardiac function; * Considered unfit for the study by the Principal Investigator; * Employee or family member of the sponsor or the clinical study site personnel.

Design outcomes

Primary

MeasureTime frameDescription
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationUp to 56 days post first doseThe number of participants experiencing at least one adverse event (AE), at least one serious adverse event (SAE) and study drug discontinuation (due to any reason).

Secondary

MeasureTime frameDescription
Pharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing regimen (Q3W/Q4W)Pharmacokinetic profiles for patisiran (ALN-TTR02) were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
Pharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing regimen (Q3W/Q4W)Pharmacokinetic profiles for patisiran (ALN-TTR02) were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
Pharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing frequencyPharmacokinetic profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
Percentage Change From Baseline in Serum Transthyretin (TTR) ProteinBaseline to Day 21/28 and Day 42/56 depending on dosing regimen (Q3W/Q4W)Percentage change of TTR relative to pretreatment/baseline levels is reported. For arms with a dosing regimen of Q4W TTR protein samples were measured on Days 28 and 56. For the arms with a dosing regimen of Q3W TTR protein samples were measured on Days 21 and 42.
Pharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing frequencyPharmacokinetic profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
Pharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)Predose (within 1 h of planned dosing start) and post-infusion at 0-6 h (pooled) on Day 0 and Day 21/28 depending on dosing frequencyPharmacokinetic profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
Pharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing frequencyPharmacokinetic profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.

Countries

Brazil, France, Germany, Portugal, Spain, Sweden, United States

Participant flow

Recruitment details

A total of 29 subjects were enrolled

Participants by arm

ArmCount
Patisiran 0.010 mg/kg Q4W
Participants received 0.010 mg/kg of patisiran (ALN-TTR02) every four weeks (Q4W).
4
Patisiran 0.050 mg/kg Q4W
Participants received 0.050 mg/kg of patisiran (ALN-TTR02) every four weeks.
3
Patisiran 0.150 mg/kg Q4W
Participants received 0.150 mg/kg of patisiran (ALN-TTR02) every four weeks.
3
Patisiran 0.300 mg/kg Q4W
Participants received 0.300 mg/kg of patisiran (ALN-TTR02) every four weeks.
7
Patisiran 0.300 mg/kg Q3W
Participants received 0.300 mg/kg of patisiran (ALN-TTR02) every three weeks (Q3W).
3
Patisiran 0.300 mg/kg Q3W Alternative
Participants received 0.300 mg/kg of patisiran (ALN-TTR02) every three weeks with alternative premedication regimen.
9
Total29

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005
Overall StudyDosing Suspended by Sponsor100000
Overall StudyProtocol Violation000100
Overall StudyWithdrawal by Subject000001

Baseline characteristics

CharacteristicPatisiran 0.010 mg/kg Q4WTotalPatisiran 0.300 mg/kg Q3W AlternativePatisiran 0.300 mg/kg Q3WPatisiran 0.300 mg/kg Q4WPatisiran 0.150 mg/kg Q4WPatisiran 0.050 mg/kg Q4W
Age, Continuous65.8 years
STANDARD_DEVIATION 8.96
55.6 years
STANDARD_DEVIATION 15.61
54.7 years
STANDARD_DEVIATION 16.34
51.0 years
STANDARD_DEVIATION 16.09
58.7 years
STANDARD_DEVIATION 16.07
41.7 years
STANDARD_DEVIATION 2.52
55.7 years
STANDARD_DEVIATION 24.83
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
4 Participants29 Participants9 Participants3 Participants7 Participants3 Participants3 Participants
Sex: Female, Male
Female
1 Participants9 Participants2 Participants1 Participants4 Participants1 Participants0 Participants
Sex: Female, Male
Male
3 Participants20 Participants7 Participants2 Participants3 Participants2 Participants3 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
deaths
Total, all-cause mortality
0 / 40 / 30 / 30 / 70 / 30 / 9
other
Total, other adverse events
1 / 43 / 32 / 37 / 73 / 37 / 9
serious
Total, serious adverse events
0 / 40 / 30 / 31 / 70 / 31 / 9

Outcome results

Primary

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation

The number of participants experiencing at least one adverse event (AE), at least one serious adverse event (SAE) and study drug discontinuation (due to any reason).

Time frame: Up to 56 days post first dose

Population: Intent-to-treat (ITT) population included all participants, who received at least 1 dose of study drug.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Patisiran 0.010 mg/kg Q4WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationAt Least 1 SAE0 Participants
Patisiran 0.010 mg/kg Q4WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationAt Least 1 AE1 Participants
Patisiran 0.010 mg/kg Q4WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationStudy Drug Discontinuation For Any Reason1 Participants
Patisiran 0.050 mg/kg Q4WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationAt Least 1 SAE0 Participants
Patisiran 0.050 mg/kg Q4WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationAt Least 1 AE3 Participants
Patisiran 0.050 mg/kg Q4WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationStudy Drug Discontinuation For Any Reason0 Participants
Patisiran 0.150 mg/kg Q4WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationAt Least 1 SAE0 Participants
Patisiran 0.150 mg/kg Q4WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationAt Least 1 AE2 Participants
Patisiran 0.150 mg/kg Q4WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationStudy Drug Discontinuation For Any Reason0 Participants
Patisiran 0.300 mg/kg Q4WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationAt Least 1 SAE1 Participants
Patisiran 0.300 mg/kg Q4WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationAt Least 1 AE7 Participants
Patisiran 0.300 mg/kg Q4WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationStudy Drug Discontinuation For Any Reason0 Participants
Patisiran 0.300 mg/kg Q3WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationAt Least 1 SAE0 Participants
Patisiran 0.300 mg/kg Q3WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationAt Least 1 AE3 Participants
Patisiran 0.300 mg/kg Q3WNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationStudy Drug Discontinuation For Any Reason0 Participants
Patisiran 0.300 mg/kg Q3W AlternativeNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationAt Least 1 AE7 Participants
Patisiran 0.300 mg/kg Q3W AlternativeNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationStudy Drug Discontinuation For Any Reason1 Participants
Patisiran 0.300 mg/kg Q3W AlternativeNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug DiscontinuationAt Least 1 SAE1 Participants
Secondary

Percentage Change From Baseline in Serum Transthyretin (TTR) Protein

Percentage change of TTR relative to pretreatment/baseline levels is reported. For arms with a dosing regimen of Q4W TTR protein samples were measured on Days 28 and 56. For the arms with a dosing regimen of Q3W TTR protein samples were measured on Days 21 and 42.

Time frame: Baseline to Day 21/28 and Day 42/56 depending on dosing regimen (Q3W/Q4W)

Population: ITT population included all participants, who received at least 1 dose of study drug.

ArmMeasureGroupValue (MEAN)Dispersion
Patisiran 0.010 mg/kg Q4WPercentage Change From Baseline in Serum Transthyretin (TTR) ProteinDay 42 or 56-20.3 PercentageStandard Deviation 20.27
Patisiran 0.010 mg/kg Q4WPercentage Change From Baseline in Serum Transthyretin (TTR) ProteinDay 21 or 28-8.9 PercentageStandard Deviation 9.91
Patisiran 0.050 mg/kg Q4WPercentage Change From Baseline in Serum Transthyretin (TTR) ProteinDay 42 or 56-14.6 PercentageStandard Deviation 15.8
Patisiran 0.050 mg/kg Q4WPercentage Change From Baseline in Serum Transthyretin (TTR) ProteinDay 21 or 28-21.7 PercentageStandard Deviation 1.69
Patisiran 0.150 mg/kg Q4WPercentage Change From Baseline in Serum Transthyretin (TTR) ProteinDay 42 or 56-44.7 PercentageStandard Deviation 12.11
Patisiran 0.150 mg/kg Q4WPercentage Change From Baseline in Serum Transthyretin (TTR) ProteinDay 21 or 28-51.6 PercentageStandard Deviation 22.84
Patisiran 0.300 mg/kg Q4WPercentage Change From Baseline in Serum Transthyretin (TTR) ProteinDay 21 or 28-73.9 PercentageStandard Deviation 8.41
Patisiran 0.300 mg/kg Q4WPercentage Change From Baseline in Serum Transthyretin (TTR) ProteinDay 42 or 56-62.8 PercentageStandard Deviation 25.11
Patisiran 0.300 mg/kg Q3WPercentage Change From Baseline in Serum Transthyretin (TTR) ProteinDay 42 or 56-78.7 PercentageStandard Deviation 9.77
Patisiran 0.300 mg/kg Q3WPercentage Change From Baseline in Serum Transthyretin (TTR) ProteinDay 21 or 28-78.0 PercentageStandard Deviation 7.55
Patisiran 0.300 mg/kg Q3W AlternativePercentage Change From Baseline in Serum Transthyretin (TTR) ProteinDay 21 or 28-80.7 PercentageStandard Deviation 10.14
Patisiran 0.300 mg/kg Q3W AlternativePercentage Change From Baseline in Serum Transthyretin (TTR) ProteinDay 42 or 56-73.3 PercentageStandard Deviation 19.55
Secondary

Pharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)

Pharmacokinetic profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.

Time frame: Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing frequency

Population: The pharmacokinetic (PK) population included all participants, who received at least one dose of patisiran and had adequate data to determine a full pharmacokinetic profile. For PK outcome measures the two arms for patisiran 0.300 mg/kg at a dosing frequency of Q3W were combined and reported irrespective of premedication regimen.

ArmMeasureGroupValue (MEAN)Dispersion
Patisiran 0.010 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)Day 00.169 L/kgStandard Deviation 0.092
Patisiran 0.010 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)Day 21 or 280.264 L/kg—
Patisiran 0.050 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)Day 00.279 L/kgStandard Deviation 0.0896
Patisiran 0.050 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)Day 21 or 280.397 L/kg—
Patisiran 0.150 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)Day 00.428 L/kg—
Patisiran 0.150 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)Day 21 or 280.305 L/kgStandard Deviation 0.163
Patisiran 0.300 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)Day 21 or 280.587 L/kgStandard Deviation 0.251
Patisiran 0.300 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)Day 00.360 L/kgStandard Deviation 0.197
Patisiran 0.300 mg/kg Q3WPharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)Day 00.588 L/kgStandard Deviation 0.305
Patisiran 0.300 mg/kg Q3WPharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)Day 21 or 280.881 L/kgStandard Deviation 0.539
Secondary

Pharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)

Pharmacokinetic profiles for patisiran (ALN-TTR02) were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.

Time frame: Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing regimen (Q3W/Q4W)

Population: The pharmacokinetic (PK) population included all participants, who received at least one dose of patisiran and had adequate data to determine a full pharmacokinetic profile. For PK outcome measures the two arms for patisiran 0.300 mg/kg at a dosing frequency of Q3W were combined and reported irrespective of premedication regimen.

ArmMeasureGroupValue (MEAN)Dispersion
Patisiran 0.010 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)Day 02738 ng*h/mLStandard Deviation 3159
Patisiran 0.010 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)Day 21 or Day 282799 ng*h/mLStandard Deviation 2645
Patisiran 0.050 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)Day 09604 ng*h/mLStandard Deviation 10588
Patisiran 0.050 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)Day 21 or Day 284884 ng*h/mLStandard Deviation 4652
Patisiran 0.150 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)Day 21 or Day 2827748 ng*h/mLStandard Deviation 17081
Patisiran 0.150 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)Day 018998 ng*h/mLStandard Deviation 5066
Patisiran 0.300 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)Day 21 or Day 2830013 ng*h/mLStandard Deviation 15935
Patisiran 0.300 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)Day 053724 ng*h/mLStandard Deviation 35814
Patisiran 0.300 mg/kg Q3WPharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)Day 039741 ng*h/mLStandard Deviation 33373
Patisiran 0.300 mg/kg Q3WPharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)Day 21 or Day 2825958 ng*h/mLStandard Deviation 28460
Secondary

Pharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)

Pharmacokinetic profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.

Time frame: Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing frequency

Population: The pharmacokinetic (PK) population included all participants, who received at least one dose of patisiran and had adequate data to determine a full pharmacokinetic profile. For PK outcome measures the two arms for patisiran 0.300 mg/kg at a dosing frequency of Q3W were combined and reported irrespective of premedication regimen.

ArmMeasureGroupValue (MEAN)Dispersion
Patisiran 0.010 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)Day 059.5 hour (h)Standard Deviation 59.3
Patisiran 0.010 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)Day 21 or 2888.1 hour (h)—
Patisiran 0.050 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)Day 039.6 hour (h)Standard Deviation 34.8
Patisiran 0.050 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)Day 21 or 2839.4 hour (h)Standard Deviation 34.8
Patisiran 0.150 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)Day 052.2 hour (h)—
Patisiran 0.150 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)Day 21 or 2846.9 hour (h)Standard Deviation 6.05
Patisiran 0.300 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)Day 21 or 2850.2 hour (h)Standard Deviation 32.7
Patisiran 0.300 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)Day 048 hour (h)Standard Deviation 23.7
Patisiran 0.300 mg/kg Q3WPharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)Day 059.3 hour (h)Standard Deviation 17.2
Patisiran 0.300 mg/kg Q3WPharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)Day 21 or 2853.8 hour (h)Standard Deviation 15.2
Secondary

Pharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)

Pharmacokinetic profiles for patisiran (ALN-TTR02) were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.

Time frame: Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing regimen (Q3W/Q4W)

Population: The pharmacokinetic (PK) population included all participants, who received at least one dose of patisiran and had adequate data to determine a full pharmacokinetic profile. For PK outcome measures the two arms for patisiran 0.300 mg/kg at a dosing frequency of Q3W were combined and reported irrespective of premedication regimen.

ArmMeasureGroupValue (MEAN)Dispersion
Patisiran 0.010 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)Day 0145 ng/mLStandard Deviation 23.4
Patisiran 0.010 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)Day 21 or 28106 ng/mLStandard Deviation 36.6
Patisiran 0.050 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)Day 21 or 28683 ng/mLStandard Deviation 391
Patisiran 0.050 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)Day 0672 ng/mLStandard Deviation 473
Patisiran 0.150 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)Day 02560 ng/mLStandard Deviation 295
Patisiran 0.150 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)Day 21 or 283243 ng/mLStandard Deviation 986
Patisiran 0.300 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)Day 06053 ng/mLStandard Deviation 1326
Patisiran 0.300 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)Day 21 or 283782 ng/mLStandard Deviation 1259
Patisiran 0.300 mg/kg Q3WPharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)Day 21 or 283314 ng/mLStandard Deviation 1253
Patisiran 0.300 mg/kg Q3WPharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)Day 04539 ng/mLStandard Deviation 1362
Secondary

Pharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)

Pharmacokinetic profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.

Time frame: Predose (within 1 h of planned dosing start) and post-infusion at 0-6 h (pooled) on Day 0 and Day 21/28 depending on dosing frequency

Population: The pharmacokinetic (PK) population included all participants, who received at least one dose of patisiran and had adequate data to determine a full pharmacokinetic profile. For PK outcome measures the two arms for patisiran 0.300 mg/kg at a dosing frequency of Q3W were combined and reported irrespective of premedication regimen.

ArmMeasureGroupValue (MEAN)Dispersion
Patisiran 0.010 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)Day 21 or 280.0320 mL/h/kgStandard Deviation 0.0555
Patisiran 0.010 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)Day 00.0153 mL/h/kgStandard Deviation 0.0307
Patisiran 0.050 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)Day 00.0268 mL/h/kgStandard Deviation 0.0465
Patisiran 0.050 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)Day 21 or 280.253 mL/h/kgStandard Deviation 0.439
Patisiran 0.150 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)Day 00.0129 mL/h/kgStandard Deviation 0.0223
Patisiran 0.150 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)Day 21 or 280.0410 mL/h/kgStandard Deviation 0.071
Patisiran 0.300 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)Day 00.0329 mL/h/kgStandard Deviation 0.05
Patisiran 0.300 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)Day 21 or 280.0652 mL/h/kgStandard Deviation 0.0893
Patisiran 0.300 mg/kg Q3WPharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)Day 00.0334 mL/h/kgStandard Deviation 0.0631
Patisiran 0.300 mg/kg Q3WPharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)Day 21 or 280.0563 mL/h/kgStandard Deviation 0.0979
Secondary

Pharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)

Pharmacokinetic profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.

Time frame: Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing frequency

Population: The pharmacokinetic (PK) population included all participants, who received at least one dose of patisiran and had adequate data to determine a full pharmacokinetic profile. For PK outcome measures the two arms for patisiran 0.300 mg/kg at a dosing frequency of Q3W were combined and reported irrespective of premedication regimen.

ArmMeasureGroupValue (MEAN)Dispersion
Patisiran 0.010 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)Day 00.0163 L/h/kgStandard Deviation 0.0248
Patisiran 0.010 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)Day 21 or 280.0211 L/h/kgStandard Deviation 0.0325
Patisiran 0.050 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)Day 00.123 L/h/kgStandard Deviation 0.205
Patisiran 0.050 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)Day 21 or 280.0844 L/h/kgStandard Deviation 0.134
Patisiran 0.150 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)Day 00.00883 L/h/kg—
Patisiran 0.150 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)Day 21 or 280.00658 L/h/kgStandard Deviation 0.00324
Patisiran 0.300 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)Day 21 or 280.0190 L/h/kgStandard Deviation 0.0233
Patisiran 0.300 mg/kg Q4WPharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)Day 00.00851 L/h/kgStandard Deviation 0.00606
Patisiran 0.300 mg/kg Q3WPharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)Day 00.0130 L/h/kgStandard Deviation 0.0105
Patisiran 0.300 mg/kg Q3WPharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)Day 21 or 280.0222 L/h/kgStandard Deviation 0.0138

Source: ClinicalTrials.gov · Data processed: Mar 15, 2026