ILLUMINATE C - Evaluate Lumasiran in Patients with Advanced PH1
Research type
Research Study
Full title
ILLUMINATE-C: A Single Arm Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Lumasiran in Patients with Advanced Primary Hyperoxaluria Type 1 (PH1)
IRAS ID
266892
Contact name
Shabbir Moochhala
Contact email
Sponsor organisation
Alnylam Pharmaceticals, Inc
Eudract number
2019-001346-17
Duration of Study in the UK
5 years, 6 months, 22 days
Research summary
PH1 is a rare genetic disease which effects predominantly the liver and ultimately the kidneys. It is characterised by the excessive production by the liver of a small molecule called oxalate, and is caused by a mutation in a gene. The oxalate mixes with small molecule called Calcium, which crystallise in the urinary tract, causing the formation of painful kidney stones, infections and ultimately kidney disease and failure.
Alnylam Pharmaceutical, Inc., is developing an injection called ‘Lumasiran’ (ALN-GO1). It is thought that lumasiran may reduce the production of harmful oxalate and symptoms of PH1.
This is a global phase 3 study, approximately 16 patients from 37 weeks gestational age up to an undefined age limit are expected to be enrolled across 15 clinical study centres in 10 countries. All eligible patients will be administered open-label lumasiran; no control group will be assessed.
The study consists of 3 parts:
- Screening Period (2 months)
- Primary Analysis Period (6 months)
- Long-term extension period (54 months)The study will include 2 cohorts: Cohort A and Cohort B. Cohort A will include patients who do not yet require dialysis. Cohort B will include patients who are on dialysis therapy. Dialysis therapy will be restricted to patients on haemodialysis only. Cohort A patients who experience a progression of renal impairment over time and begin to require dialysis therapy will cross-over to Cohort B.
From Screening to Day 1, patients will have 4 plasma oxalate collections to establish a robust baseline measurement for plasma oxalate.
The study medicine Lumasiran will be administered subcutaneously using weight-based dosing.
The purpose of the study is to evaluate the effect of lumasiran on plasma oxalate in patients who are not on dialysis therapy and in patients who are on dialysis therapy.
Lay summary of study results: ILLUMINATE-C (ALN-GO1-005)
Summary of Clinical Study Results
A Study of Lumasiran in Participants with Advanced Primary Hyperoxaluria Type 1Thank You
We thank the participants and caregivers for taking part in Study ALN-GO1-005, also called ILLUMINATE-C. Study participation allows Alnylam and the doctors, nurses, and staff conducting the study to evaluate how well lumasiran works and how safe it is in treating people with PH1.OVERVIEW
ILLUMINATE-C studied a new medicine called lumasiran (lu-MAH-si-ran) for participants with advanced Primary Hyperoxaluria Type 1 (PH1).
This document is a brief summary of the study and its results. This study was open to participants of all ages, including newborns who had reached full term in pregnancy. The main purpose of this study was to find out whether lumasiran lowers oxalate levels in participants with PH1.What is PH1?
PH1 is a rare disease that is inherited, meaning it is passed down from parents to children. It affects a person’s liver and makes their body produce too much of a substance called oxalate. The body cannot break down oxalate, so it builds up in the kidneys. This may cause kidney stones or other medical problems and over time may lead to kidney failure.
In severe cases, PH1 may also damage other parts of the person’s body. Some people with severe symptoms may need dialysis, a liver transplant, or a combined liver and kidney transplant.
Dialysis is a treatment that removes extra fluid and waste from the blood when the kidneys don’t work well.
A healthy person’s liver makes a small amount of oxalate that the body can use. In people with PH1, oxalate mixes with calcium to form calcium oxalate, which causes kidney stones, leading to irreparable damage and ultimately, kidney failure. When oxalate can no longer be removed through the kidneys, it moves to other organs including the eyes, bones, skin, and heart.About lumasiran
Lumasiran is a medicine that reduces the ability of liver cells to make a protein called glycolate oxidase (GO). GO plays a role in the high levels of oxalate in people with PH1.
This study and others like it show that lumasiran lowers the amount of GO and therefore lowers the levels of oxalate in people with PH1. Lowering oxalate reduces the symptoms of PH1.WHY WAS THIS RESEARCH NEEDED?
There were no approved medicines for PH1 when the study started. People may have treated symptoms of PH1 by drinking lots of fluids, taking vitamin B6 treatment, and taking medicine to lower the formation of kidney stones.
Some participants were receiving dialysis during this study. Researchers were interested in understanding how lumasiran works in people who were receiving dialysis. Therefore, the study included 2 groups with impaired kidney function. Group A included 6 participants who were not receiving dialysis, and Group B included 15 participants who were receiving dialysis.
Blood is made of 2 parts: cells and liquid. The liquid part of blood is called plasma.
The main goals of the ILLUMINATE-C study were to answer the following questions:
• Does lumasiran lower the amount of oxalate in plasma for Group A participants not receiving dialysis during the first 6 months of the study?
• Does lumasiran lower the amount of oxalate in plasma for Group B participants receiving dialysis during the first 6 months of the study?
• Does lumasiran cause medical problems?WHO TOOK PART IN THE STUDY?
There were 21 participants in the study. 12 were male (57%) and 9 were female (43%) . When the study began, the youngest participant was 4 months old and the oldest participant was 59 years old.
There were 13 study sites in Australia, Belgium, France, Israel, Jordan, Lebanon, Netherlands, Turkey, United Arab Emirates, and United States. This study started in January 2020 and ended in June 2025.
Age of Participants: Less than 2 years (19%), 2 to less than 6 years (14%), 6 to less than 18 years (38%), 18 years and older (29%)
Race of Participants: Asian (19%), White (76%), Other (5%)
Weight of participants: Less than 10Kg (29%), Between 10 and 20 Kg (19%), 20 Kg or more (52%)
WHAT HAPPENED DURING THE STUDY?
Study doctors checked participants to make sure they could join the study. The doctors collected blood samples from each person to measure the amount of oxalate that was in the plasma before taking the study medicine. People with oxalate above a certain level could be part of the study.
The study had 2 parts, called the Primary Treatment Period and the Extension Period. The amount of lumasiran given to each participant was based on their weight. The screening period lasted 120 days and 21 participants were enrolled in the study. After completing the 6-month Primary Treatment Period, all 21 participants continued to receive study medicine in the Extension Period for up to 4 and a half years (54 months).
Study doctors checked participants’ overall health and asked them how they were feeling throughout the study. Participants or their caregivers answered questions in interviews and completed questionnaires so the doctors could check whether their symptoms changed. The doctors also regularly checked participants’ health and took note of any important medical problems, called adverse events.During the Extension Period, 7 participants left the study: 5 had a combined liver and kidney transplant and 2 participants left for other reasons. A total of 14 participants completed the study.
How was lumasiran given?
All participants received lumasiran as an injection under the skin in the stomach area. The doctor may have also used the upper arms or thighs.
Participants were divided into 3 groups based on their weight and given doses of 3 mg/kg or 6 mg/kg lumasiran. Study medicine was given to each weight group using 2 dosing schedules, a Starting Dose and an Ongoing Dose.
• Weight group Less than 10 Kg: starting dose (6mg/kg once a month for 3 months) – Ongoing Dose (3mg/kg monthly)
• Weight group Between 10 and 20 Kg: starting dose (6mg/kg once a month for 3 months) – Ongoing Dose (6mg/kg once every 3 months)
• Weight group More than 20 Kg: starting dose (6mg/kg once a month for 3 months) – Ongoing Dose (6mg/kg once every 3 months)WHAT WERE THE RESULTS OF THE STUDY?
Did lumasiran lower the amount of oxalate in plasma?
Lumasiran lowered plasma oxalate levels in both Group A and Group B. Average oxalate levels went down each month during the Primary Treatment Period compared to the start of the study (called baseline). Overall, plasma oxalate levels went down by 33% in Group A and 42% in Group B after 6 months.
Participants in Group B had more severe symptoms of PH1 and were receiving dialysis when the study began. Their plasma oxalate levels were higher at baseline compared to participants in Group A, who were not receiving dialysis. As a result, lumasiran had a greater effect on oxalate levels for participants in Group B.What adverse events did participants have during the study?
An adverse event is any medical problem that a participant has during a study. Study doctors record all adverse events. Adverse events may be caused by the health condition, by a medicine, by chance, or by an unknown cause. Study doctors decide if adverse events may be related to the study medicine.
An adverse event is considered serious when it:
• Is life-threatening or causes death
• Causes lasting problems
• Requires a hospital stayHow many participants had adverse events?
All 21 participants in the study had adverse events. Of these, 7 participants had adverse events that were thought to be related to lumasiran.
• Most of the adverse events that were related to lumasiran included skin reactions at or near the injection site.
• These were mild and did not last long (transient).
The total number of adverse events for each group of participants during all periods of the study (up to 5 years) is described below:
• Group A: 6 out of 6 participants reported a total of 94 adverse events. Of these, 3 adverse events were thought to be related to lumasiran.
• Group B: 15 out of 15 participants reported a total of 302 adverse events. Of these, 15 adverse events were thought to be related to lumasiran.What were the most common adverse events during the study?
The adverse events reported by at least 15% of all participants during all periods of the study (up to 5 years) is described below. The percentage for Group A refers to the Number (%) of Participants out of 6 Participants and for Group B to the Number (%) of Participants out of 15 Participants:
Fever: Group A: 1 (17%) – Group B: 8 (53%)
Diarrhea: Group A: 1 (17%) – Group B: 6 (40%)
Stomach flu: Group A: 2 (33%) – Group B: 5 (33%)
Kidney transplant: Group A: 1 (17%) – Group B: 6 (40%)
Infection in the nose, throat and airways: Group A: 3 (50%) – Group B: 3 (20%)
Vomiting: Group A: 2 (33%) – Group B: 4 (27%)
Low level of red blood cells: Group A: 2 (33%) – Group B: 3 (20%)
Skin reactions at or near the injection site: Group A: 1 (17%) – Group B: 4 (27%)
COVID-19: Group A: 1 (17%) – Group B: 3 (20%)
Eye infection: Group A: 0 – Group B: 4 (27%)
Ear infection: Group A: 0 – Group B: 4 (27%)
Infection in the urinary tract: Group A: 1 (17%) – Group B: 3 (20%)How Many Participants Had a Serious Adverse Event?
The most common serious adverse events overall included fever, kidney transplant, and combined liver and kidney transplant. 3 participants stopped taking lumasiran because of a serious adverse event (combined liver and kidney transplant due to PH1). The study doctor reviewed all serious adverse events.
- Group A: 5 out of 6 participants reported a total of 15 serious adverse events; none were thought to be related to lumasiran
- Group B: 14 out of 15 participants reported a total of 84 serious adverse events; none were thought to be related to lumasiranWhat were the Most Common Adverse Events during the Study?
Two participants died during the study.
• 1 participant had a sudden stop of the heart (called cardiac arrest) during the Screening Period.
• 1 participant died when their heart and lungs stopped working; this happened after the participant had left the study.
The study doctor confirmed that these serious events were not related to lumasiran.HOW HAS THIS STUDY HELPED PATIENTS AND RESEARCHERS?
ILLUMINATE-C was a study that helped researchers learn about using lumasiran in people with PH1 who have impaired kidney function, including those receiving dialysis. The results of ILLUMINATE-C showed that lumasiran reduced the amount of oxalate in plasma and did not cause any unexpected adverse events when taken for up to about 5 years.
It is important to remember that this summary shows results from one study and may not represent all the information known about how lumasiran works. Other studies may have different results.WHERE CAN I LEARN MORE ABOUT THE ILLUMINATE-C STUDY?
For more details on this study please speak with a doctor, or visit:
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C02%7Clondonbridge.rec%40hra.nhs.uk%7C69ebe5e6539d4f4cd64d08de4c61cb4b%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639032180065355562%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=%2BSCxgwVeMmeSABb76%2Fct92aiJpF5DmTSaFLY7zGok58%3D&reserved=0
Use the study identifier NCT04152200
https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Feuclinicaltrials.eu%252Fsearch-for-clinical-trials%2FNBTI%2FooTCAQ%2FAQ%2Fde3898b2-7cd0-41b4-b6c0-e2769597b678%2F3%2F_6Gnusqh74&data=05%7C02%7Clondonbridge.rec%40hra.nhs.uk%7C69ebe5e6539d4f4cd64d08de4c61cb4b%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639032180065372212%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=OU3Xvt0YcX%2Br1HqD3xQ90RYzW%2B51R9ozTd1zTdc7q0k%3D&reserved=0
Use the study identifier 2023-503382-29-00FULL TITLE: ILLUMINATE-C: A Single Arm Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Lumasiran in Patients with Advanced Primary Hyperoxaluria Type 1 (PH1)
Alnylam Pharmaceuticals 675 W Kendall Street Cambridge, MA 02142 United States clinicaltrials@alnylam.com
1-877-256-9526We appreciate our patients’ participation in the ILLUMINATE-C program!
Has the registry been updated to include summary results?: Yes
If yes - please enter the URL to summary results: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT04152200%253Fterm%253DLumasiran%252520in%252520Patients%252520with%252520Advanced%252520Primary%252520Hyperoxaluria%252520Type%2525201%252520&data=05%7C02%7Clondonbridge.rec%40hra.nhs.uk%7C69ebe5e6539d4f4cd64d08de4c61cb4b%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639032180065388313%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=8zeAwF1Ek5S0DBvzu%2BFCXq2yT2DGmfvhETjMd713uSE%3D&reserved=0(PH1)%26rank%3D1%26tab%3Dresults/NBTI/ooTCAQ/AQ/de3898b2-7cd0-41b4-b6c0-e2769597b678/4/D8NWxyuVqIREC name
London - London Bridge Research Ethics Committee
REC reference
19/LO/1903
Date of REC Opinion
22 Jan 2020
REC opinion
Further Information Favourable Opinion