A Phase 1 Study of Givosiran (ALN-AS1) in Patients With Acute Intermittent Porphyria (AIP)
Primary Purpose
Acute Intermittent Porphyria
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
givosiran (ALN-AS1)
Sterile Normal Saline (0.9% NaCl)
Sponsored by
About this trial
This is an interventional treatment trial for Acute Intermittent Porphyria focused on measuring RNAi therapeutic, Porphyria, AIP
Eligibility 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
Sites / Locations
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
givosiran (ALN-AS1)
Sterile Normal Saline (0.9% NaCl)
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Profile of Pharmacokinetics (PK) of givosiran
Cmax
Profile of Pharmacokinetics (PK) of givosiran
tmax
Profile of Pharmacokinetics (PK) of givosiran
AUC
Profile of Pharmacokinetics (PK) of givosiran
t1/2
The change in delta-aminolevulinic acid (ALA) from baseline
The change in Porphobilinogen (PBG) from baseline
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02452372
Brief Title
A Phase 1 Study of Givosiran (ALN-AS1) in Patients With Acute Intermittent Porphyria (AIP)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
May 6, 2015 (Actual)
Primary Completion Date
September 6, 2017 (Actual)
Study Completion Date
September 6, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alnylam Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Intermittent Porphyria
Keywords
RNAi therapeutic, Porphyria, AIP
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
givosiran (ALN-AS1)
Arm Type
Active Comparator
Arm Title
Sterile Normal Saline (0.9% NaCl)
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
givosiran (ALN-AS1)
Intervention Description
Single or multiple doses of ALN-AS1 by subcutaneous (sc) injection
Intervention Type
Drug
Intervention Name(s)
Sterile Normal Saline (0.9% NaCl)
Intervention Description
calculated volume to match active comparator
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Profile of Pharmacokinetics (PK) of givosiran
Description
Cmax
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
Title
Profile of Pharmacokinetics (PK) of givosiran
Description
tmax
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
Title
Profile of Pharmacokinetics (PK) of givosiran
Description
AUC
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
Title
Profile of Pharmacokinetics (PK) of givosiran
Description
t1/2
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
Title
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
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy Simon, MD
Organizational Affiliation
Alnylam Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Trial Site
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
Clinical Trial Site
City
San Francisco
State/Province
California
Country
United States
Facility Name
Clinical Trial Site
City
New York
State/Province
New York
Country
United States
Facility Name
Clinical Trial Site
City
Galveston
State/Province
Texas
Country
United States
Facility Name
Clinical Trial Site
City
Stockholm
Country
Sweden
Facility Name
Clinical Trial Site
City
London
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
30726693
Citation
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.
Results Reference
derived
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A Phase 1 Study of Givosiran (ALN-AS1) in Patients With Acute Intermittent Porphyria (AIP)
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