Osilodrostat for Cushing's Disease

Recruiting at 13 trial locations

Overseen By Recordati

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must not be taking: Cortisol-lowering drugs, Investigational drugs

Disqualifiers: Macroadenoma, Hypercortisolism, Body weight <30kg, others

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of osilodrostat (also known as LCI-699 or Isturisa) in children and teens with Cushing's syndrome, a condition characterized by excessive cortisol production. Researchers aim to understand how the body processes the drug and its impact on the condition. Eligible participants include children or teens with Cushing's syndrome who have undergone unsuccessful surgery, are awaiting surgery, or cannot have surgery immediately. This trial may suit those experiencing noticeable changes in growth and weight due to the syndrome. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for any drugs used to lower cortisol levels, which is 5 half-lives of the drug. If you're taking investigational drugs, you must stop them 30 days before joining the trial or after a washout period of at least 5 half-lives, whichever is longer.

Is there any evidence suggesting that osilodrostat is likely to be safe for children and adolescents with Cushing's syndrome?

Research has shown that osilodrostat, also known as LCI699, is generally well-tolerated by people with Cushing's disease. In a study with 137 patients who took at least one dose of osilodrostat, the treatment proved safe over 48 weeks. Most participants did not experience serious side effects. Common side effects included fatigue, nausea, and headaches, which were usually mild.

Osilodrostat is already approved for adults with Cushing's syndrome, indicating its safety. However, this trial focuses on children and teenagers, making it important to observe their response. Overall, previous research suggests that osilodrostat is safe for many people with Cushing's disease. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Cushing's disease, which often involve surgery or medications like ketoconazole that inhibit cortisol production broadly, osilodrostat (LCI699) is unique because it specifically targets the enzyme 11β-hydroxylase. This enzyme is crucial in the final step of cortisol synthesis, making osilodrostat more focused in its action. Researchers are excited about this treatment because it offers a potentially more precise way to reduce excess cortisol levels, which could lead to fewer side effects and improved effectiveness compared to existing therapies.

What evidence suggests that osilodrostat might be an effective treatment for Cushing's syndrome?

Research has shown that osilodrostat, the treatment under study in this trial, is an effective option for Cushing's disease. One study found that 77% of patients had their cortisol levels, often elevated in Cushing's, return to normal. Another study demonstrated that osilodrostat quickly and consistently lowered cortisol levels. The treatment is generally well-tolerated, meaning most patients can take it without major issues. Overall, these findings suggest osilodrostat can be a strong option for managing Cushing's disease. ^{4 6 7 8 9}

Who Is on the Research Team?

Recordati AG

Principal Investigator

Recordati AG

Are You a Good Fit for This Trial?

This trial is for children and adolescents with Cushing's disease who have either failed surgery, are waiting for it, or can't have it yet. They should show signs of the disease like growth issues despite weight gain and must be able to swallow tablets. Consent from parents or guardians is required.

Inclusion Criteria

I have Cushing's disease and surgery didn't work, is pending, or isn't an option for me.

My growth has slowed down while I've gained weight, and doctors suspect I might have Cushing's disease.

Parents or legal guardians able to provide consent/assent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment

Participants receive osilodrostat for pharmacokinetics, pharmacodynamics, and tolerability evaluation

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Optional 9-month extension period for participants benefiting from therapy, assessing PD activity and safety/tolerability

9 months

What Are the Treatments Tested in This Trial?

Interventions

• LCI699

Trial Overview The study tests Osilodrostat (LCI699), focusing on how the drug moves in the body (PK), its effects on the disease (PD), and its safety in young patients with Cushing's disease. It's an open-label study, meaning everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: LCI699 (osilodrostat) Experimental Treatment 1 Intervention

Subjects with cushing's syndrome taking LCI699 (osilodrostat)

LCI699 is already approved in European Union, United States for the following indications:

Approved in European Union as Isturisa for:

• Cushing's disease

Approved in United States as Isturisa for:

• Cushing's disease

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

RECORDATI GROUP

Lead Sponsor

Trials

13

Recruited

4,500+

Published Research Related to This Trial

Osilodrostat is a moderate inhibitor of the CYP1A2 and CYP2C19 enzymes, and a weak inhibitor of CYP2D6 and CYP3A4, which are important for drug metabolism.

The study suggests that osilodrostat is unlikely to significantly increase the exposure of other medications cleared by CYP3A4, making it a safer option for patients with Cushing's disease who may be on multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Interaction Potential of Osilodrostat (LCI699) Based on Its Effect on the Pharmacokinetics of Probe Drugs of Cytochrome P450 Enzymes in Healthy Adults. Armani, S., Ting, L., Sauter, N., et al.[2020]

Osilodrostat is an oral medication that works by inhibiting the enzyme 11β-hydroxylase, which is crucial in the production of cortisol, making it a targeted treatment for Cushing's disease.

It has been approved in the EU for treating endogenous Cushing's syndrome in adults based on positive results from a pivotal phase III trial, and it is currently under review in the USA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osilodrostat: First Approval. Duggan, S.[2020]

Osilodrostat is an effective oral treatment for endogenous Cushing's syndrome, showing excellent efficacy in controlling hypercortisolism based on multiple studies, including LINC1, LINC2, and LINC3.

While osilodrostat is generally well-tolerated, it carries risks such as adrenal insufficiency, hypokalemia, and potential pituitary tumor enlargement, necessitating careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osilodrostat oral tablets for adults with Cushing's disease. Martino, M., Aboud, N., Lucchetti, B., et al.[2022]

In a 48-week Phase III clinical trial involving 60 patients with Cushing's disease, osilodrostat demonstrated long-term efficacy, with 72.4% of patients achieving normalized urinary free cortisol levels by the end of the trial.

Osilodrostat was well tolerated and maintained improvements in clinical signs and physical manifestations of hypercortisolism, indicating it is a safe and effective long-term treatment option for Cushing's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of osilodrostat in patients with Cushing's disease: results from the LINC 4 study extension. Gadelha, M., Snyder, PJ., Witek, P., et al.[2023]

Osilodrostat is an effective treatment for Cushing disease, rapidly reducing 24-hour urinary free cortisol levels and improving related health parameters such as glycemia, blood pressure, body weight, and quality of life.

While osilodrostat has tolerable adverse effects, including adrenal insufficiency and hypokalemia, careful monitoring and a slower dose increase can help manage these risks, especially due to potential drug interactions that may cause QT prolongation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osilodrostat: A Review of Recent Clinical Studies and Practical Recommendations for its Use in the Treatment of Cushing Disease. Yuen, KCJ.[2021]

Osilodrostat is an effective treatment for Cushing's disease, significantly reducing 24-hour mean urinary free cortisol levels in 86% of participants in a pivotal phase 3 study, compared to 29% in the placebo group.

While osilodrostat is generally safe, it requires careful monitoring for potential side effects like QT interval prolongation and increased cortisol precursors, which can lead to complications such as hypokalemia and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osilodrostat: A Novel Steroidogenesis Inhibitor to Treat Cushing's Disease. Dougherty, JA., Desai, DS., Herrera, JB.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9202723/

Randomized Trial of Osilodrostat for the Treatment of Cushing ... This randomized, placebo-controlled trial demonstrates that osilodrostat is a highly effective treatment for Cushing disease, normalizing UFC excretion in 77% ...

2. isturisa.com isturisa.com/hcp/clinical-studies/

Clinical Studies Osilodrostat is an effective and well-tolerated treatment option for patients with Cushing's disease (CD): final results from the LINC3 study.

3. academic.oup.com academic.oup.com/ejendo/advance-article/doi/10.1093/ejendo/lvaf207/8276112

Osilodrostat dose impact on efficacy/safety in Cushing's disease Osilodrostat provided rapid reductions in 24-h mean urinary free cortisol (mUFC) levels, which were maintained for long periods.8,11-15 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02180217

NCT02180217 | Safety and Efficacy of LCI699 for the ... The study aimed to confirm long-term efficacy and safety of LCI699 for the treatment of patients with Cushing's disease.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01331239?term=LCI699&viewType=Table&rank=9

Safety and Efficacy of LCI699 in Cushing's Disease Patients This exploratory study is a proof of concept study to determine whether LCI699 can safely reduce the level of urinary free cortisol in patients with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02697734

Efficacy and Safety Evaluation of Osilodrostat in Cushing's ... The purpose of this study was to confirm efficacy and safety of osilodrostat for the treatment of patients with Cushing's disease who are candidates for medical ...

7. isturisa.com isturisa.com/hcp/safety-profile/

Safety Profile A well-tolerated safety profile demonstrated through 48 weeks1. Adverse reactions among 137 patients with Cushing's disease (CD) who received at least 1 dose of ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12055610/

Osilodrostat for Cushing syndrome - PMC Osilodrostat offers a new therapeutic option for patients with endogenous Cushing syndrome who have been unsuccessful with surgery or unable to receive surgery.

9. ema.europa.eu ema.europa.eu/en/documents/product-information/isturisa-epar-product-information_en.pdf

Isturisa, INN-osilodrostat - EMA Clinical efficacy and safety. The efficacy and safety of osilodrostat in patients with endogenous Cushing's syndrome in adults were evaluated in two phase ...