What side effects are associated with this type of intervention?

Lumasiran, an RNA interference therapy targeting the HAO1 gene to reduce oxalate production, is being studied for its efficacy and safety in treating Primary Hyperoxaluria Type 1. Common side effects of similar treatments may include injection site reactions, abdominal pain, and mild gastrointestinal symptoms. Broader treatments for Primary Hyperoxaluria can also lead to potential side effects such as kidney stones, urinary tract infections, and in severe cases, renal impairment. It is important to discuss these potential side effects with a healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

Lumasiran is an RNA interference therapeutic targeting the HAO1 gene to reduce oxalate production in patients with Primary Hyperoxaluria Type 1 (PH1). Prior to Lumasiran, the FDA approved Oxlumo (lumasiran) in November 2020 as the first treatment specifically for PH1. This approval marked a significant advancement in the management of PH1, as it directly addresses the underlying metabolic defect by reducing the production of oxalate, thereby preventing the formation of kidney stones and other complications associated with the disease.

What other types of research exist?

Promising novel alternatives to Lumasiran for Primary Hyperoxaluria patients include: 1) Nedosiran, another RNA interference therapy targeting the LDHA gene to reduce oxalate production. 2) Stiripentol, a small molecule that has shown potential in reducing oxalate levels. 3) CRISPR-Cas9 based gene editing therapies targeting genes involved in oxalate metabolism. These alternatives are in various stages of clinical trials and may offer new options for PH1 treatment in 2024.

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RNAi Therapeutics

Lumasiran for Primary Hyperoxaluria (ILLUMINATE-C Trial)

Phase 3

Waitlist Available

Research Sponsored by Alnylam Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Has documented diagnosis of primary hyperoxaluria type 1 (PH1)

Must not have

Diagnosis of conditions other than PH1 contributing to renal insufficiency

History of kidney transplant and currently receiving immunosuppressants

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to month 60

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a medication called lumasiran for patients with a severe genetic disorder called Advanced Primary Hyperoxaluria Type 1 (PH1). The medication works by lowering the amount of a harmful substance called oxalate that the liver produces, which can help protect the kidneys and other organs.

Who is the study for?

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.

What is being tested?

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).

What are the potential side effects?

While not explicitly listed here, potential side effects of Lumasiran may include reactions at the injection site, allergic responses, kidney-related issues due to changes in urine composition after treatment, and general discomforts such as headache or nausea.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with primary hyperoxaluria type 1.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have had a kidney transplant and am on immunosuppressants.

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I have had a liver transplant.

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I am on dialysis, either hemodialysis with peritoneal or just peritoneal.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to month 60

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to month 60

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to month 60 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Cohort A: Percent Change in Plasma Oxalate From Baseline to Month 6

Cohort B: Percent Change in Pre-dialysis Plasma Oxalate From Baseline to Month 6

Secondary study objectives

Absolute Change in Plasma Oxalate From Baseline to Month 6

Apparent Clearance (CL/F) of Lumasiran

Apparent Volume of Distribution (V/F) of Lumasiran

+16 more

Side effects data

From 2024 Phase 3 trial • 39 Patients • NCT03681184

35%

Injection site reaction

31%

Abdominal pain

19%

Headache

15%

Nasopharyngitis

15%

COVID-19

15%

Injection site pain

12%

Oropharyngeal pain

12%

Flank pain

12%

Urinary tract infection

12%

Renal pain

12%

Injection site erythema

12%

Upper respiratory tract infection

12%

Pyrexia

12%

Vaccination site pain

12%

Dysuria

12%

Alopecia

Nephrolithiasis

Procedural pain

Fatigue

Abdominal pain upper

Immunisation reaction

Vomiting

Cough

Rhinitis

Pneumonia

Nausea

Back pain

Constipation

Dizziness

Rhinorrhoea

Injection site discomfort

Hypersensitivity

Dacryostenosis acquired

Post-traumatic pain

Gastroenteritis

Oedema peripheral

Abdominal pain lower

Fungal skin infection

Weight gain poor

Groin pain

Vitamin D deficiency

Migraine

Erythema

Rash

Gastroenteritis viral

Blepharitis

Hepatomegaly

Milk allergy

Asymptomatic COVID-19

Tooth infection

Iron deficiency anaemia

Herpes simplex reactivation

Ovarian cyst

Nasal congestion

Ear pain

Influenza like illness

Pyelonephritis

Corneal abrasion

Livedo reticularis

Rash erythematous

Skin lesion

Vaccination site swelling

Bronchitis

Pyelonephritis acute

Tonsillitis

Nail injury

Presyncope

Hand fracture

Vision blurred

Furuncle

Infected bite

Weight increased

Arthralgia

Pruritus

Irritability

Hypertension

Renal impairment

Eye pain

Herpes zoster

Separation anxiety disorder

Post abortion haemorrhage

Fungal foot infection

Weight decreased

Restless legs syndrome

Testicular pain

Skin hyperpigmentation

Foot fracture

Skin abrasion

White coat hypertension

Thalassaemia beta

Musculoskeletal chest pain

Urinary incontinence

Post procedural infection

Post procedural complication

Abdominal discomfort

Urosepsis

Follicular lymphoma

Abdominal tenderness

Diarrhoea

Gastrooesophageal reflux disease

Asthenia

Chest pain

Ear infection

Onychomycosis

Pharyngitis

Pyelitis

Viral sinusitis

Skin laceration

Sunburn

Tibia fracture

Cardiac murmur

Protein urine present

Gout

Disturbance in attention

Hypoaesthesia

Anxiety

Attention deficit hyperactivity disorder

Enuresis

Fear of injection

Haematuria

Hypertonic bladder

Polyuria

Productive cough

Dry skin

Eczema

100%

80%

60%

40%

20%

Study treatment Arm

Lumasiran/Lumasiran

Placebo/Lumasiran

Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

1Treatment groups

Experimental Treatment

Group I: LumasiranExperimental Treatment1 Intervention

All patients will receive open-label lumasiran.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Lumasiran

2019

Completed Phase 3

~130

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Primary Hyperoxaluria (PH) aim to reduce oxalate production, which is the primary cause of the disease. Lumasiran, an RNA interference therapy, exemplifies this approach by targeting the HAO1 gene. This gene encodes glycolate oxidase, an enzyme crucial for oxalate production. By silencing the HAO1 gene, Lumasiran reduces the enzyme's activity, thereby decreasing oxalate production. This reduction in oxalate is vital for PH patients as it helps prevent the accumulation of oxalate in the kidneys, reducing the risk of kidney stones and other severe renal complications.

Modulatory effect of 4-phenyl butyric acid on hyperoxaluria-induced renal injury and inflammation.Oxalate-induced changes in renal epithelial cell function: role in stone disease.