Lumasiran for Primary Hyperoxaluria

(ILLUMINATE-C Trial)

No longer recruiting at 16 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Alnylam Pharmaceuticals

Must not be taking: Immunosuppressants

Disqualifiers: Liver transplant, Kidney transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new treatment, lumasiran, for individuals with Primary Hyperoxaluria Type 1 (PH1), a rare condition that affects the kidneys. The study aims to determine if lumasiran is safe and effective in managing PH1. All participants will receive the treatment to assess its impact on the body. Ideal candidates for this trial are those diagnosed with PH1 who have significant kidney issues, particularly if they have been on a stable dialysis or Vitamin B6 regimen. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking Vitamin B6 or are on hemodialysis, you must have been on a stable regimen for a certain period before joining the trial.

Is there any evidence suggesting that lumasiran is likely to be safe for humans?

Research has shown that lumasiran is safe for people with Primary Hyperoxaluria Type 1 (PH1). In long-term studies, patients taking lumasiran experienced significantly lower oxalate levels, a positive outcome. Oxalate can lead to kidney stones and other issues if it accumulates in the body.

One study tracked patients for 24 months and found that lumasiran maintained low oxalate levels without causing unexpected side effects. Another study confirmed that kidney function remained stable during treatment. A committee regularly reviewed safety data to ensure everything remained on track.

Overall, the treatment has been well-tolerated, with no serious or unexpected side effects reported. This suggests that lumasiran is a safe option for managing PH1. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Lumasiran is unique because it targets the root cause of primary hyperoxaluria by reducing the production of oxalate, the compound that accumulates in this condition. Unlike standard treatments, which often focus on managing symptoms or complications like kidney stones, Lumasiran works by inhibiting an enzyme called glycolate oxidase, effectively lowering oxalate levels in the body. Researchers are excited about Lumasiran because it offers a more direct approach to managing the disease, potentially improving outcomes and quality of life for patients.

What evidence suggests that lumasiran might be an effective treatment for Primary Hyperoxaluria Type 1?

In people with Primary Hyperoxaluria Type 1 (PH1), research has shown that lumasiran effectively lowers oxalate production, a substance harmful to the kidneys. Studies indicate that prolonged use of lumasiran maintains low urinary oxalate levels, crucial for managing PH1. Lumasiran blocks the production of harmful proteins that contribute to the disease. The treatment has proven effective for individuals of all ages and at all stages of chronic kidney disease. Overall, lumasiran has demonstrated promising results in reducing oxalate and managing PH1 symptoms. ^{1 2 4 5 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Alnylam Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for patients with Advanced Primary Hyperoxaluria Type 1 (PH1). Eligible participants include those on stable hemodialysis for at least 4 weeks, diagnosed with PH1, meeting specific plasma oxalate levels, and if taking Vitamin B6, must have been on a consistent dose for over 90 days. Patients should have an eGFR ≤45 mL/min/1.73 m^2 or elevated serum creatinine for their age if under 12 months.

Inclusion Criteria

I have been diagnosed with primary hyperoxaluria type 1.

I have been on a stable hemodialysis regimen for at least 4 weeks.

My kidney function is low, with an eGFR of 45 or less.

Exclusion Criteria

I have kidney problems not caused by Primary Hyperoxaluria type 1.

I have had a kidney transplant and am on immunosuppressants.

I have had a liver transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive open-label lumasiran to evaluate efficacy, safety, pharmacokinetics, and pharmacodynamics

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term Follow-up

Participants' quality of life and systemic oxalosis are assessed up to 60 months

54 months

What Are the Treatments Tested in This Trial?

Interventions

• Lumasiran

Trial Overview The study tests Lumasiran's effectiveness and safety in treating PH1. It will also examine how the body processes the drug (pharmacokinetics) and its impact on the disease (pharmacodynamics).

How Is the Trial Designed?

Group I: Lumasiran Experimental Treatment 1 Intervention

All patients will receive open-label lumasiran.

Who Is Running the Clinical Trial?

Alnylam Pharmaceuticals

Lead Sponsor

Trials

81

Recruited

16,100+

Dr. Yvonne Greenstreet

Alnylam Pharmaceuticals

Chief Executive Officer since 2021

MD from the University of Leeds, MBA from INSEAD

Dr. Pushkal Garg

Alnylam Pharmaceuticals

Chief Medical Officer since 2016

MD from Columbia University

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39081738/

Efficacy and Safety of Lumasiran in Patients With Primary ... In patients with PH1, longer-term lumasiran treatment led to sustained reduction in UOx excretion, with an acceptable safety profile and encouraging clinical ...

2. kireports.org kireports.org/article/S2468-0249(24)01683-8/fulltext

Efficacy and Safety of Lumasiran in Patients With Primary ... Data from a large European study indicate that the outcome of primary hyperoxaluria type 1 correlates with the AGXT mutation type. Kidney Int ...

3. ajkd.org ajkd.org/article/S0272-6386(25)00729-2/fulltext

24-Month Follow-up of the Phase 3 ILLUMINATE-C Trial Efficacy and Safety of Lumasiran for Advanced Primary Hyperoxaluria ... data that support these results is made available 12 months after ...

4. academic.oup.com academic.oup.com/ndt/advance-article/doi/10.1093/ndt/gfaf188/8261537

Long-term lumasiran therapy final results from a Phase 2 open ... Lumasiran is the first RNA interference therapeutic approved in all age groups and CKD stages for reducing oxalate overproduction in primary ...

5. investors.alnylam.com investors.alnylam.com/press-release?id=24376

Alnylam Pharmaceuticals Press Release | Dec 17, 2019 Alnylam reports positive topline results from ILLUMINATE-A Phase 3 study of Lumasiran for the treatment of primary hyperoxaluria type 1.

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa2021712

Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria ... An independent data and safety monitoring committee reviewed pertinent safety data. Data were collected by trial investigators and were ...