Long-term Safety and Clinical Activity of ALN-AS1 in Patients with Acute Intermittent Porphyria (AIP), a rare metabolic disorder.

• Register: EUCTR
• Last refreshed on: 17 January 2022
• Main ID: EUCTR2016-002638-54-SE
• Date of registration: 09/08/2016
• Prospective Registration: Yes
• Primary sponsor: Alnylam Pharmaceuticals, Inc.
• Public title: Long-term Safety and Clinical Activity of ALN-AS1 in Patients with Acute Intermittent Porphyria (AIP), a rare metabolic disorder.
• Scientific title: A Multicenter, Open-label Extension Study to Evaluate the Long-term Safety and Clinical Activity of Subcutaneously Administered ALN-AS1 in Patients with Acute Intermittent Porphyria who have Completed a Previous Clinical Study with ALN-AS1
• Date of first enrolment: 20/12/2017
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002638-54
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Sweden, United Kingdom, United States

Contacts

• Name: Clinical Trials Hotline
• Affiliation: Alnylam Pharmaceuticals Inc

• Name: Clinical Trials Hotline
• Affiliation: Alnylam Pharmaceuticals Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Completed and, in the opinion of the Investigator, tolerated study drug dosing in Part C of study ALN-AS1-001
2. Not on a scheduled regimen of hemin to prevent porphyria attacks at Screening
3.Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test, cannot be breast feeding, and must be willing to use acceptable methods of contraception 14 days before first dose, throughout study participation, and for 90 days after last dose administration.
4. Willing and able to comply with the study requirements and to provide written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 23
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
1. Alanine transaminase =2.0×ULN or total bilirubin =2 mg/dL (unless bilirubin elevation is due to Gilbert’s syndrome)
2. Estimated glomerular filtration rate =30 mL/min/1.73 m2 (using the Modification of Diet in Renal Disease formula)
3. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or to N-acetyl galactosamine ligand
4. Received an investigational agent, other than ALN-AS1, or who are in follow-up of another clinical study of an investigational agent within 90 days before study drug administration
5. Other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Acute Intermittent Porphyria (AIP)
MedDRA version: 20.0 Level: LLT Classification code 10000818 Term: Acute intermittent porphyria System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Name: Givosiran
Product Code: ALN-AS1
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ALN-60519
CAS Number: 1639325-44-2
Current Sponsor code: ALN-60519
Other descriptive name: CAS # in D.3.9.1 for Sodium Salt. CAS number 1639325-43-1 (Parent Acid)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 189-

Primary Outcome(s)

Secondary Objective: • Assess the PD effect of ALN-AS1 over time
• Assess the clinical activity of ALN-AS1 over time

Main Objective: To evaluate the long-term safety and tolerability of ALN-AS1 in patients with AIP.

Primary end point(s): • Patient incidence of adverse events

Timepoint(s) of evaluation of this end point: The duration of treatment is up to 48 months. The estimated total time on study, inclusive of Screening/Baseline, for each patient is up to 56 months

Secondary Outcome(s)

Secondary end point(s): • Change in urine ALA and PBG levels
• Frequency and characteristics of porphyria attacks
• Change in hemin administration.

Timepoint(s) of evaluation of this end point: The duration of treatment is up to 48 months. The estimated total time on study, inclusive of Screening/Baseline, for each patient is up to 56 months

Secondary ID(s)

ALN-AS1-002

Source(s) of Monetary Support

Alnylam Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 20/12/2017
Contact: