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

Acute Intermittent Porphyria Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02452372
• Other study ID #: ALN-AS1-001
• Status: Completed
• Phase: Phase 1
• Start date: May 6, 2015
• Est. completion date: September 6, 2017

Study information

• Verified date: June 2018
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 6, 2017
• Est. primary completion date: September 6, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Intermittent Porphyria
• Porphyria, Acute Intermittent
• Porphyria, Erythropoietic
• Porphyrias

Intervention

Drug:
• givosiran (ALN-AS1)
Single or multiple doses of ALN-AS1 by subcutaneous (sc) injection
• Sterile Normal Saline (0.9% NaCl)
calculated volume to match active comparator

Locations

Country	Name	City	State
Sweden	Clinical Trial Site	Stockholm
United Kingdom	Clinical Trial Site	London
United States	Clinical Trial Site	Birmingham	Alabama
United States	Clinical Trial Site	Galveston	Texas
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

United States,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Profile of Pharmacokinetics (PK) of givosiran	Cmax	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
Secondary	Profile of Pharmacokinetics (PK) of givosiran	tmax	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
Secondary	Profile of Pharmacokinetics (PK) of givosiran	AUC	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
Secondary	Profile of Pharmacokinetics (PK) of givosiran	t1/2	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
Secondary	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
Secondary	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