The First-in-Human Study of an Investigational Drug, ALN-GO1, in Healthy Adult Subjects and Patients with Primary Hyperoxaluria Type 1 Disease

• Register: EUCTR
• Last refreshed on: 20 July 2020
• Main ID: EUCTR2015-004407-23-GB
• Date of registration: 21/12/2015
• Prospective Registration: Yes
• Primary sponsor: Alnylam Pharmaceuticals, Inc.
• Public title: The First-in-Human Study of an Investigational Drug, ALN-GO1, in Healthy Adult Subjects and Patients with Primary Hyperoxaluria Type 1 Disease
• Scientific title: A Phase 1/2, Single-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Safety, Tolerability, Pharmacokinetic and Pharmacodynamics Study of Subcutaneously Administered ALN-GO1 in Healthy Adult Subjects, and Patients with Primary Hyperoxaluria Type 1
• Date of first enrolment: 10/02/2016
• Target sample size: 52
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004407-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: yes; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Israel, Jordan, Netherlands, United Kingdom, United States

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion Criteria for Parts A and B:
1. Male and female subjects aged 18-64 years (or age of legal consent, whichever is older), inclusive (Part A) and 6-64 years, inclusive (Part B).
2. Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception.
3. Willing to provide written informed consent and to comply with study requirements.

Additional Inclusion Criteria for Part B:
4. confirmation of PH1 disease
5. 24-hour urinary oxalate excretion of >0.7 mmol/1.73m2/day.
6.Estimated GFR of >45 mL/min/1.73m2.
7. If taking Vitamin B6 (pyridoxine), must have been on stable regimen for at least 90 days
Are the trial subjects under 18? yes
Number of subjects for this age range: 16
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Exclusion Criteria for Parts A and B:
1. Any uncontrolled or serious disease, or any medical or surgical condition (with the exception of PH1 for patients in Part B) that may either interfere with participation in the clinical study, and/or put the subject at significant risk (according to the Investigator’s judgment) if he/she participates in the clinical study.
2. Mental illness, alcoholism, drug abuse, or heavy smokers and users of nicotine
3. History of multiple drug allergies or intolerance to subcutaneous injection
4. Received an investigational agent within 3 months before the first dose of study drug or are in follow-up of another clinical study
5. Known history of allergic reaction to an oligonucleotide or GalNAc
6. History of intolerance to SC injection or relevant abdominal scarring
7. Women who are pregnant or breast feeding
Part B only
8. Echocardiography (ECHO) assessment of normal left ventricular systolic function, defined as left ventricular ejection fraction <55% at screening
9. Troponin I > the upper limit of normal (ULN) at screening


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

Health Condition(s) or Problem(s) studied

Primary Hyperoxaluria Type 1 (PH1)
MedDRA version: 20.1 Level: PT Classification code 10020703 Term: Hyperoxaluria System Organ Class: 10038359 - Renal and urinary disorders

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

Intervention(s)

Product Name: ALN-GO1
Product Code: ALN-GO1
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ALN-65585
Current Sponsor code: ALN-65585
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: -To characterize the PK of ALN-GO1 in healthy adult subjects and PH1 patients

-To assess the PD effect of ALN-GO1 on plasma glycolate

Main Objective: To evaluate the safety and tolerability of single- and multiple-ascending doses of ALN-GO1, respectively, in healthy adult subjects and in patients with PH1

Primary end point(s): The safety of ALN-GO1 evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation

Timepoint(s) of evaluation of this end point: Part A (SAD phase): 1) assessed throughout to Day 57 and 2) until plasma glycolate decreases to a level that is no more than 20% above of baseline or until plasma glycolate is below the upper limit of normal

Part B (MAD phase): assessed throughout to 12 weeks (84 days) after the last dose of study drug and until either:
- enrolment into the open label extension study
- or until recovery of 24-hour urinary oxalate to >80% of baseline and recovery of plasma glycolate to <20% above baseline or = the upper limit of normal.
- or until the investigator determines that the patient can discontinue follow-up, where this is endorsed by the Safety Review Committee based upon ALN-GO1 safety data and the individual patient’s safety and pharmacodynamic data

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Part A (SAD phase): 1) assessed throughout to Day 57 and 2) until plasma glycolate decreases to a level that is no more than 20% above of baseline or until plasma glycolate is below the upper limit of normal

Part B (MAD phase): assessed throughout to 12 weeks (84 days) after the last dose of study drug and until either:
- enrolment into the open label extension study
- or until recovery of 24-hour urinary oxalate to >80% of baseline and recovery of plasma glycolate to <20% above baseline or = the upper limit of normal.
- or until the investigator determines that the patient can discontinue follow-up, where this is endorsed by the Safety Review Committee based upon ALN-GO1 safety data and the individual patient’s safety and pharmacodynamic data

Secondary end point(s): The Pharmacokinetics (PK) of ALN-GO1 (Cmax, tmax, AUC, t1/2)
The Pharmacodynamics (PD) of ALN-GO1

Secondary ID(s)

ALN-GO1-001

NCT02706886

Source(s) of Monetary Support

Alnylam Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 10/02/2016
Contact:

Results

• Results available: Yes
• Date Posted: 21/08/2019
• Date Completed: 23/01/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-004407-23/results