Clinical trial NCT02452372: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Intermittent Porphyria
Keywords: RNAi therapeutic
Porphyria
AIP
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-05-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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
timeFrame: Part A (SAD phase): through day 42; Part B (MAD) phase: through Day 70; Part C (MD) phase: through Day 168
Secondary outcomes:
measure: Profile of Pharmacokinetics (PK) of givosiran
timeFrame: 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
measure: Profile of Pharmacokinetics (PK) of givosiran
timeFrame: 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
measure: Profile of Pharmacokinetics (PK) of givosiran
timeFrame: 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
measure: Profile of Pharmacokinetics (PK) of givosiran
timeFrame: 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
measure: The change in delta-aminolevulinic acid (ALA) from baseline
timeFrame: 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
measure: The change in Porphobilinogen (PBG) from baseline
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Trial Site
state: Alabama
city: San Francisco
country: United States
facility: Clinical Trial Site
state: California
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Galveston
country: United States
facility: Clinical Trial Site
state: Texas
city: Stockholm
country: Sweden
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Amy Simon, MD
role: STUDY_DIRECTOR
References:
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.