Acute Intermittent Porphyria
Conditions
Keywords
RNAi therapeutic, 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.
Interventions
DRUGgivosiran (ALN-AS1)
Single or multiple doses of ALN-AS1 by subcutaneous (sc) injection
DRUGSterile Normal Saline (0.9% NaCl)
calculated volume to match active comparator
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 | Part A (SAD phase): through day 42; Part B (MAD) phase: through Day 70; Part C (MD) phase: through Day 168 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Profile of Pharmacokinetics (PK) of givosiran | 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 |
| The change in delta-aminolevulinic acid (ALA) from baseline | 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 | 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 | — |
Countries
Sweden, United Kingdom, United States
Outcome results
None listed