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A Study to Evaluate Long-term Safety and Clinical Activity of Givosiran (ALN-AS1) in Patient With Acute Intermittent Porphyria (AIP)

Phase 1
Completed
Conditions
Acute Intermittent Porphyria
Interventions
Registration Number
NCT02949830
Lead Sponsor
Alnylam Pharmaceuticals
Brief Summary

The purpose of this study is to determine the long-term safety, tolerability and pharmacokinetics of givosiran (ALN-AS1) in AIP patients who completed study ALN-AS1-001 (NCT02452372).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
16
Inclusion Criteria
  • Completed participation in Part C of study ALN-AS1-001 (NCT02452372)
  • Not on a scheduled regimen of hemin
  • Women of child bearing potential must have a negative serum pregnancy test, not be nursing, and use acceptable contraception
  • Willing and able to comply with the study requirements and to provide written informed consent
Exclusion Criteria
  • Clinically significant abnormal laboratory results
  • Received an investigational agent (other than ALN-AS1) within 90 days before the first dose of study drug or are in follow-up of another clinical study
  • History of multiple drug allergies or intolerance to subcutaneous injection

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
GivosiranGivosiranAt the beginning of this study, participants received either givosiran 2.5 mg/kg subcutaneous (SC) injection once monthly(QM), givosiran 5.0 mg/kg SC injection QM, or givosiran 5.0 mg/kg SC injection once every 3 months (Q3M). Within a year, all participants were transitioned to givosiran 2.5 mg/kg SC injection QM.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Adverse Events (AEs)Through Month 49

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.

Secondary Outcome Measures
NameTimeMethod
The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) as Measured by Percent Decrease From BaselineBaseline; Month 48

The PD effect of givosiran was evaluated by spot urine ALA levels normalized to spot urine creatinine levels.

Annualized Rate of Hemin AdministrationThrough Month 49

The annualized rate of hemin administration was evaluated by annualized days of hemin use, which is calculated as the number of doses of hemin administered/total person-years.

Annualized Rate of Composite Porphyria AttacksThrough Month 48

Porphyria attacks were defined as meeting all of the following criteria: an acute episode of neurovisceral pain in the abdomen, back, chest, extremities and/or limbs, no other medically determined cause, and required treatment with intravenous (IV) dextrose or hemin, carbohydrates, or analgesics, or other medications such as antiemetics at a dose or frequency beyond the participant's usual daily porphyria management. Composite porphyria attacks included porphyria attacks that required hospitalization, urgent healthcare visit, or intravenous (IV) hemin administration at home. The annualized attack rate (AAR) was calculated as the number of composite porphyria attacks/total person-years.

The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) as Measured by Percent Decrease From BaselineBaseline; Month 48

The PD effect of givosiran was evaluated by spot urine PBG levels normalized to spot urine creatinine levels.

Trial Locations

Locations (1)

Clinical Trial Site

🇬🇧

London, United Kingdom

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