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

Phase 1

Completed

• Conditions: Acute Intermittent Porphyria
• Interventions: Drug: givosiran (ALN-AS1); Drug: Sterile Normal Saline (0.9% NaCl)

• Registration Number: NCT02452372
• Lead Sponsor: Alnylam Pharmaceuticals

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 available

Study Timeline

• Study Start: 2015-05-06
• Study First Submitted: 2015-05-19
• Study First Submitted QC: 2015-05-20
• Study First Posted: 2015-05-22
• Primary Completion: 2017-09-06
• Study Completion: 2017-09-06
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-13
• Last Update Posted: 2018-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
givosiran (ALN-AS1)	givosiran (ALN-AS1)	-
Sterile Normal Saline (0.9% NaCl)	Sterile Normal Saline (0.9% NaCl)	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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	t1/2
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

Trial Locations

Locations (1)

Clinical Trial Site; 🇬🇧 London, United Kingdom