NCT02452372

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started May 2015

Typical duration for phase_1

Geographic Reach
3 countries

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 6, 2015

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

May 19, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 22, 2015

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 6, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 6, 2017

Completed
Last Updated

June 14, 2018

Status Verified

June 1, 2018

Enrollment Period

2.3 years

First QC Date

May 19, 2015

Last Update Submit

June 13, 2018

Conditions

Acute Intermittent Porphyria

Keywords

RNAi therapeuticPorphyriaAIP

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (6)

  • 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

  • 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

  • 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

  • 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

  • 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

  • +1 more secondary outcomes

Study Arms (2)

givosiran (ALN-AS1)

ACTIVE COMPARATOR
Drug: givosiran (ALN-AS1)

Sterile Normal Saline (0.9% NaCl)

PLACEBO COMPARATOR
Drug: Sterile Normal Saline (0.9% NaCl)

Interventions

givosiran (ALN-AS1)DRUG

Single or multiple doses of ALN-AS1 by subcutaneous (sc) injection

givosiran (ALN-AS1)
Sterile Normal Saline (0.9% NaCl)DRUG

calculated volume to match active comparator

Sterile Normal Saline (0.9% NaCl)

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • 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.
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Clinical Trial Site

Birmingham, Alabama, United States

Location

Clinical Trial Site

San Francisco, California, United States

Location

Clinical Trial Site

New York, New York, United States

Location

Clinical Trial Site

Galveston, Texas, United States

Location

Clinical Trial Site

Stockholm, Sweden

Location

Clinical Trial Site

London, United Kingdom

Location

Related Publications (2)

  • Sardh E, Balwani M, Rees DC, Anderson KE, Jia G, Sweetser MT, Wang B. Long-term follow-up of givosiran treatment in patients with acute intermittent porphyria from a phase 1/2, 48-month open-label extension study. Orphanet J Rare Dis. 2024 Oct 3;19(1):365. doi: 10.1186/s13023-024-03284-w.

    PMID: 39363243DERIVED

  • 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.

    PMID: 30726693DERIVED

MeSH Terms

Conditions

Porphyria, Acute IntermittentPorphyrias

Interventions

givosiran

Condition Hierarchy (Ancestors)

Porphyrias, HepaticLiver DiseasesDigestive System DiseasesSkin Diseases, GeneticGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesSkin DiseasesSkin and Connective Tissue DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • Amy Simon, MD

    Alnylam Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 19, 2015

First Posted

May 22, 2015

Study Start

May 6, 2015

Primary Completion

September 6, 2017

Study Completion

September 6, 2017

Last Updated

June 14, 2018

Record last verified: 2018-06

Locations

SE(1)US(4)GB(1)