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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Study Description
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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.

Condition or disease Intervention/treatment Phase
Acute Intermittent Porphyria Drug: givosiran (ALN-AS1) Drug: Sterile Normal Saline (0.9% NaCl) Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : May 6, 2015
Actual Primary Completion Date : September 6, 2017
Actual Study Completion Date : September 6, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Porphyria

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: givosiran (ALN-AS1) Drug: givosiran (ALN-AS1)
Single or multiple doses of ALN-AS1 by subcutaneous (sc) injection
Placebo Comparator: Sterile Normal Saline (0.9% NaCl) Drug: Sterile Normal Saline (0.9% NaCl)
calculated volume to match active comparator


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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 ]
  6. 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 ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02452372


Locations
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United States, Alabama
Clinical Trial Site
Birmingham, Alabama, United States
United States, California
Clinical Trial Site
San Francisco, California, United States
United States, New York
Clinical Trial Site
New York, New York, United States
United States, Texas
Clinical Trial Site
Galveston, Texas, United States
Sweden
Clinical Trial Site
Stockholm, Sweden
United Kingdom
Clinical Trial Site
London, United Kingdom
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
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Study Director: Amy Simon, MD Alnylam Pharmaceuticals
More Information
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02452372    
Other Study ID Numbers: ALN-AS1-001
First Posted: May 22, 2015    Key Record Dates
Last Update Posted: June 14, 2018
Last Verified: June 2018
Keywords provided by Alnylam Pharmaceuticals:
RNAi therapeutic
Porphyria
AIP
Additional relevant MeSH terms:
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Porphyria, Acute Intermittent
Porphyria, Erythropoietic
Porphyrias
Metabolic Diseases
Skin Diseases, Genetic
 Genetic Diseases, Inborn
Skin Diseases
Porphyrias, Hepatic
Liver Diseases
Digestive System Diseases