ILLUMINATE-C: A Single Arm Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Lumasiran in Patients with Advanced Primary Hyperoxaluria Type 1 (PH1)

Cohorts A and B
1. Have reached at least 37 weeks estimated gestational age (full-term infant)
at consent (or assent).
2. Documentation or confirmation of PH1 as determined by genetic analysis prior
to initial dosing.
3. Patients with eGFR <=45 mL/min/1.73 m2 as calculated by the MDRD formula if
>=18 years or Schwartz Bedside Formula if >=12 months to <18 years, or
patients <12 months of age with serum creatinine that is considered elevated
for age at consent.
4. The mean of the three most recent plasma oxalatesamples collected prior to
Day 1 is >=20 µmol/L. In Cohort B, these 3 collections may include the first
pre-dialysis sample from each plasma oxalate profile.
5. If taking therapeutic vitamin B6 (pyridoxine), must have been on stable
regimen for at least 90 days before consent, and is able and willing to remain
on this stable regimen until at least the Month 6 visit.
Dose adjustments for interval weight gain are acceptable.
6. Patient is willing and able to comply with the study requirements and to
provide written informed consent. In the case of patients under the age of
legal consent, the legal guardian(s) must provide informed consent and the
patient should provide assent per local and national requirements.

Cohort B Only
1. On a stable hemodialysis regimen for at least 4 weeks prior to Screening
plasma oxalate assessment; able and willing to maintain this regimen through
Month 6 visit, with changes to dialysis regimen permitted only when medically
indicated.

1. Has any of the following laboratory parameter assessments at Screening:
a. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2× ULN
for
age
b. Total bilirubin >1.5×ULN. Patients with elevated total bilirubin that is
secondary to
documented Gilbert*s syndrome are eligible if the total bilirubin is <2× ULN
c. International normalized ratio (INR) >1.5 for patients not on
anticoagulants. Patients
on oral anticoagulants (eg, warfarin) with an INR <3.5 will be allowed.
d. Hemoglobin <8.0 mg/dL
2. Has known active human immunodeficiency virus (HIV) infection; or evidence
of current
or chronic hepatitis C virus (HCV) or hepatitis B (HBV) infection.
3. Received an investigational agent within the last 30 days or 5 half-lives,
whichever is
longer, prior to the first dose of study drug, or are in follow-up of another
clinical study
during Screening. Consultation with the Medical Monitor is required if treated
with
unapproved products prior to consent regardless of the time interval prior to
the first dose
of study drug.
4. Known history of allergic reaction to an oligonucleotide or GalNAc.
5. Diagnosis of conditions other than PH1 contributing to renal insufficiency
such as glomerulonephritis, nephrotic syndrome, or lupus nephritis.
6. Any condition or comorbidity, which in the opinion of the Investigator,
would make the
patient unsuitable for dosing or would interfere with study compliance, data
interpretation, patient safety, and/or patient participation in the study. This
includes
significant active and poorly controlled (unstable) cardiovascular, neurologic,
gastrointestinal, endocrine, renal or psychiatric disorders unrelated to PH1
identified by
key laboratory abnormalities or medical history.
7. Unwilling or unable to limit alcohol consumption throughout the course of
the study.
Alcohol intake of >2 units/day is excluded during the study (unit: 1 glass of
wine
[approximately 125 mL] = 1 measure of spirits [approximately 1 fluid ounce] = *
pint of
beer [approximately 284 mL].
8. History of alcohol abuse, within the last 12 months before screening, in the
opinion of the
investigator.
9. Patients with a previous liver transplant or for whom a liver transplant is
anticipated in
the next 6 months.
10. Patients with a previous kidney transplant who are currently receiving
immunosuppression to prevent transplant rejection.
11. Patients maintained on a peritoneal dialysis regimen.
12. Patients who in the opinion of the Investigator plan to start dialysis
replacement therapy
in the next 6 months.
13. Any comorbidity or condition that, in the opinion of the Investigator, is
anticipated to
prevent participation in at least 12 months of the study.
14. Is not willing to comply with the contraceptive requirements during the
study period, as
described in Section 5.5.1.
15. Female patient is pregnant, planning a pregnancy, or breast feeding.