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

Overview

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).

Full Title of Study: “A Multicenter, Open-label Extension Study to Evaluate the Long-term Safety and Clinical Activity of Subcutaneously Administered ALN-AS1 in Patients With Acute Intermittent Porphyria Who Have Completed a Previous Clinical Study With ALN-AS1”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 5, 2021

Interventions

  • Drug: Givosiran
    • Givosiran by subcutaneous (SC) injection.

Arms, Groups and Cohorts

  • Experimental: Givosiran
    • At 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.

Clinical Trial Outcome Measures

Primary Measures

  • Percentage of Participants With Adverse Events (AEs)
    • Time Frame: 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 Measures

  • The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) as Measured by Percent Decrease From Baseline
    • Time Frame: Baseline; Month 48
    • The PD effect of givosiran was evaluated by spot urine ALA levels normalized to spot urine creatinine levels.
  • The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) as Measured by Percent Decrease From Baseline
    • Time Frame: Baseline; Month 48
    • The PD effect of givosiran was evaluated by spot urine PBG levels normalized to spot urine creatinine levels.
  • Annualized Rate of Composite Porphyria Attacks
    • Time Frame: Through 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.
  • Annualized Rate of Hemin Administration
    • Time Frame: Through 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.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Alnylam Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Director, Study Director, Alnylam Pharmaceuticals

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