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A Phase 1 Study of Givosiran (ALN-AS1) in Patients With Acute Intermittent Porphyria (AIP)

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ClinicalTrials.gov Identifier: NCT02452372
Recruitment Status : Completed
First Posted : May 22, 2015
Last Update Posted : June 14, 2018
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE May 19, 2015
First Posted Date  ICMJE May 22, 2015
Last Update Posted Date June 14, 2018
Actual Study Start Date  ICMJE May 6, 2015
Actual Primary Completion Date September 6, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2018)
The safety of givosiran evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation [ Time Frame: Part A (SAD phase): through day 42; Part B (MAD) phase: through Day 70; Part C (MD) phase: through Day 168 ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 20, 2015)
The safety of ALN-AS1 evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation [ Time Frame: Part A (SAD phase): through day 42; Part B (MAD) phase: through Day 70; Part C (MD) phase: through Day 126 ]
Change History Complete list of historical versions of study NCT02452372 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2018)
  • Profile of Pharmacokinetics (PK) of givosiran [ Time Frame: Part A (SAD) phase: predose - 42 days post-dose; Part B (MAD) phase: predose - 70 days post-dose; Part C (MD) phase: predose - 168 days post-dose ]
    Cmax
  • Profile of Pharmacokinetics (PK) of givosiran [ Time Frame: Part A (SAD) phase: predose - 42 days post-dose; Part B (MAD) phase: predose - 70 days post-dose; Part C (MD) phase: predose - 168 days post-dose ]
    tmax
  • Profile of Pharmacokinetics (PK) of givosiran [ Time Frame: Part A (SAD) phase: predose - 42 days post-dose; Part B (MAD) phase: predose - 70 days post-dose; Part C (MD) phase: predose - 168 days post-dose ]
    AUC
  • Profile of Pharmacokinetics (PK) of givosiran [ Time Frame: Part A (SAD) phase: predose - 42 days post-dose; Part B (MAD) phase: predose - 70 days post-dose; Part C (MD) phase: predose - 168 days post-dose ]
    t1/2
  • The change in delta-aminolevulinic acid (ALA) from baseline [ Time Frame: Part A (SAD) phase: screening - 42 days post-dose; Part B (MAD) phase: screening - 70 days post-dose; Part C (MD) phase: screening - 168 days post-dose ]
  • The change in Porphobilinogen (PBG) from baseline [ Time Frame: Part A (SAD) phase: screening - 42 days post-dose; Part B (MAD) phase: screening - 70 days post-dose; Part C (MD) phase: screening - 168 days post-dose ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2015)
  • Profile of Pharmacokinetics (PK) of ALN-AS1 [ Time Frame: Part A (SAD) phase: predose - 42 days post-dose; Part B (MAD) phase: predose - 70 days post-dose; Part C (MD) phase: predose - 126 days post-dose ]
    Cmax, tmax, AUC, t1/2
  • The change in delta-aminolevulinic acid (ALA) and Porphobilinogen (PBG) from baseline [ Time Frame: Part A (SAD) phase: screening - 42 days post-dose; Part B (MAD) phase: screening - 70 days post-dose; Part C (MD) phase: screening - 126 days post-dose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1 Study of Givosiran (ALN-AS1) in Patients With Acute Intermittent Porphyria (AIP)
Official Title  ICMJE A Phase 1, Single-ascending Dose, Multiple-ascending Dose, and Multi-dose Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN AS1 in Patients With Acute Intermittent Porphyria (AIP)
Brief Summary The purpose of this study is to evaluate the safety and tolerability of givosiran (ALN-AS1) in AIP patients as well as to characterize pharmacokinetics (PK) and pharmacodynamics (PD) of ALN-AS1 in AIP patients.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Acute Intermittent Porphyria
Intervention  ICMJE
  • Drug: givosiran (ALN-AS1)
    Single or multiple doses of ALN-AS1 by subcutaneous (sc) injection
  • Drug: Sterile Normal Saline (0.9% NaCl)
    calculated volume to match active comparator
Study Arms  ICMJE
  • Active Comparator: givosiran (ALN-AS1)
    Intervention: Drug: givosiran (ALN-AS1)
  • Placebo Comparator: Sterile Normal Saline (0.9% NaCl)
    Intervention: Drug: Sterile Normal Saline (0.9% NaCl)
Publications * Sardh E, Harper P, Balwani M, Stein P, Rees D, Bissell DM, Desnick R, Parker C, Phillips J, Bonkovsky HL, Vassiliou D, Penz C, Chan-Daniels A, He Q, Querbes W, Fitzgerald K, Kim JB, Garg P, Vaishnaw A, Simon AR, Anderson KE. Phase 1 Trial of an RNA Interference Therapy for Acute Intermittent Porphyria. N Engl J Med. 2019 Feb 7;380(6):549-558. doi: 10.1056/NEJMoa1807838.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 7, 2017)
40
Original Estimated Enrollment  ICMJE
 (submitted: May 20, 2015)
48
Actual Study Completion Date  ICMJE September 6, 2017
Actual Primary Completion Date September 6, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Parts A and B

Inclusion Criteria:

  • Diagnosis of AIP
  • Urine PBG at Screening indicating patient is a high excreter
  • No clinically significant health concerns
  • Women of child bearing potential must have a negative pregnancy test, not be nursing, and use effective contraception
  • Willing to provide written informed consent and willing to comply with study requirements.

Exclusion Criteria:

  • Porphyria attack within 6 months of screening
  • Started a new prescription medication within 3 months of screening
  • Clinically significant abnormal laboratory results
  • Received an investigational agent 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

Part C

Inclusion Criteria:

  • Diagnosis of AIP
  • Patient experienced a porphyria attack or was taking medication to prevent attacks recently
  • No clinically significant health concerns
  • Women of child bearing potential must have a negative pregnancy test, not be nursing, and use effective contraception
  • Willing to provide written informed consent and willing to comply with study requirements.

Exclusion Criteria:

  • Stared a new prescription medication within 3 months of screening
  • Clinically significant abnormal laboratory results
  • Received an investigational agent 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02452372
Other Study ID Numbers  ICMJE ALN-AS1-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alnylam Pharmaceuticals
Study Sponsor  ICMJE Alnylam Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Amy Simon, MD Alnylam Pharmaceuticals
PRS Account Alnylam Pharmaceuticals
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP