ITU512 for Sickle Cell Disease

Overseen By Novartis Pharmaceuticals

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Novartis Pharmaceuticals

Must not be taking: Hydroxyurea

Disqualifiers: Arrhythmias, Significant illness, others

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

Compensation: Varies

Number of Visits: Unknown

161 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ITU512 for individuals with sickle cell disease, a blood disorder that causes red blood cells to become misshapen and sticky, blocking blood flow. The trial aims to determine if ITU512 is safe, how it behaves in the body, and whether it can increase fetal hemoglobin, which may reduce sickle cell symptoms. The study consists of different parts: healthy participants will help assess safety and how the body processes the drug, while patients with sickle cell disease will help evaluate its potential to improve their condition. Individuals with sickle cell disease who are not using hydroxyurea and are interested in trying new treatments might be suitable for this trial. As a Phase 1, Phase 2 trial, the study focuses on understanding how ITU512 works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

If you are currently using hydroxyurea or hydroxycarbamide, you will need to stop taking it to participate in this trial. The protocol does not specify about other medications.

Is there any evidence suggesting that ITU512 is likely to be safe for humans?

Research indicates that ITU512 is still under testing, but some hints about its safety have emerged. The treatment is currently in early clinical trials, so information on its tolerability remains limited. However, its progression to a Phase 1/Phase 2 trial suggests that ITU512 showed enough promise in lab studies to warrant human testing. This phase primarily focuses on safety and determining the correct dose.

Studies of similar treatments, such as hydroxyurea for sickle cell disease, have shown that the medication is generally safe for both children and adults. Although ITU512 differs, this comparison offers some hope regarding its safety. The main goal now is to assess how well people tolerate the treatment and monitor for any side effects. As the trial progresses, more detailed safety information will become available. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell disease?

Unlike standard treatments for sickle cell disease, which typically focus on managing symptoms and preventing complications, ITU512 offers a new approach that directly targets the underlying causes of the disease. Researchers are particularly excited about ITU512 because it has a novel mechanism of action that could potentially modify the disease process itself, rather than just alleviating symptoms. This could mean fewer pain episodes and a significant improvement in the quality of life for patients with sickle cell disease. The unique approach of ITU512 positions it as a promising candidate in the pursuit of more effective treatments for this challenging condition.

What evidence suggests that ITU512 might be an effective treatment for sickle cell disease?

Research suggests that ITU512, studied in this trial, might help treat sickle cell disease by boosting levels of fetal hemoglobin (HbF). Fetal hemoglobin can prevent red blood cells from becoming sickle-shaped, the main issue in sickle cell disease. ITU512 acts like a "molecular glue," targeting a protein called WIZ. By increasing HbF, ITU512 aims to reduce the symptoms and complications of sickle cell disease. Although data from human studies is still being gathered, this method has shown promise in similar treatments. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for healthy individuals and those with sickle cell disease. Participants must meet specific health criteria to join, but the exact inclusion and exclusion details are not provided here.

Inclusion Criteria

I have been diagnosed with sickle cell disease.

Part 1: Participants must be in good health as determined by the investigator's assessment of medical history, physical examination, vital signs, ECG, and laboratory tests

I weigh at least 50 kg and my BMI is between 18.0-32.0.

Exclusion Criteria

I have a history of irregular heartbeats.

I have been healthy for the last two weeks.

Part 1: QTcF ≥ 450 msec (as a mean value of triplicates)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

First-in-human study to assess safety, tolerability, and pharmacokinetics of ITU512 in healthy participants

Up to 60 days

Multiple visits for dose administration and monitoring

Phase II Treatment

Evaluation of safety, tolerability, pharmacokinetics, and efficacy of ITU512 in patients with sickle cell disease

Up to 5 months

Regular visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Optional extension part for continued evaluation of ITU512 in patients with sickle cell disease

What Are the Treatments Tested in This Trial?

Interventions

• ITU512

Trial Overview The study is testing ITU512's safety, how it's tolerated by the body, its movement through the body (pharmacokinetics), effect on food intake, and ability to increase fetal hemoglobin in both healthy people and those with sickle cell disease.

How Is the Trial Designed?

Group I: Part 2 Experimental Treatment 2 Interventions

Part 2 in patients with sickle cell disease

Group II: Part 1C Experimental Treatment 1 Intervention

Part 1C in healthy participants

Group III: Part 1B Experimental Treatment 2 Interventions

Part 1B in healthy participants

Group IV: Part 1A Experimental Treatment 2 Interventions

Part 1A in healthy participants

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

Published Research Related to This Trial

Genomic research can significantly advance the development of curative therapies for sickle cell disease (SCD) by focusing on the genetic factors that influence fetal hemoglobin (HbF) levels, especially in diverse African populations.

Investing in RNA therapies, such as microRNA and messenger RNA approaches, could enhance HbF production and address cardiovascular complications associated with SCD, ultimately reducing mortality rates in affected adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future of sickle cell disease therapeutics rests in genomics. Wonkam, A.[2023]

Hydroxyurea (HU) is effective in reducing complications of sickle cell disease (SCD) in children, with a study of 127 patients showing low rates of acute chest syndromes and cerebrovascular events over 426 patient-years of follow-up.

In a subgroup of 32 patients followed for 6 years, HU demonstrated significant benefits, and among 72 patients assessed for stroke risk, only 1 experienced a cerebrovascular event, suggesting HU may help prevent strokes even in very young children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydroxyurea for sickle cell disease in children and for prevention of cerebrovascular events: the Belgian experience. Gulbis, B., Haberman, D., Dufour, D., et al.[2022]

In a study of 523 pediatric patients with sickle cell disease, those treated with hydroxyurea (HU) were more likely to experience organ-specific complications, such as cardiovascular, hepatic, renal, and pulmonary issues, compared to those not treated with HU.

Despite the increased likelihood of complications in the HU-treated group, the study concluded that HU is not associated with the development of serious adverse events, suggesting it can be safely administered to severely ill children with sickle cell disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical complications in severe pediatric sickle cell disease and the impact of hydroxyurea. Tripathi, A., Jerrell, JM., Stallworth, JR.[2022]

A Phase I/II trial involving 84 children aged 5 to 15 years with sickle cell anemia demonstrated that hydroxyurea (HU) therapy is safe, with no life-threatening adverse events and no instances of growth failure.

HU treatment led to significant positive changes in blood parameters, such as increased hemoglobin and fetal hemoglobin levels, while laboratory toxicities were generally mild and reversible, indicating its potential efficacy in managing sickle cell anemia in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Pediatric Hydroxyurea Group. Kinney, TR., Helms, RW., O'Branski, EE., et al.[2021]

Hydroxyurea (HU) significantly reduced the rate of vaso-occlusive crises, blood transfusion needs, and hospitalizations in patients with HbSβ(+)-thalassemia after 2 years of treatment, demonstrating its efficacy in managing this condition.

The treatment led to notable improvements in hematological parameters, such as increased %HbF and hemoglobin levels, with minimal toxicity observed, making HU a safe and effective option for patients in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low and fixed dose of hydroxyurea is effective and safe in patients with HbSβ(+) thalassemia with IVS1-5(G→C) mutation. Dehury, S., Purohit, P., Patel, S., et al.[2022]

Citations

1. novartis.com novartis.com/clinicaltrials/study/nct06546670

A Phase I/II Study of ITU512 in Healthy Participants and ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary food effect of ITU512 as well as ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06546670

NCT06546670 | A Phase I/II Study of ITU512 in Healthy ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary food effect of ITU512 as well as the fetal ...

3. withpower.com withpower.com/trial/itu512-for-sickle-cell-disease-76ce5

ITU512 for Sickle Cell Disease Hydroxyurea (HU) is effective in reducing complications of sickle cell disease (SCD) in children, with a study of 127 patients showing low rates of acute chest ...

4. synapse.patsnap.com synapse.patsnap.com/drug/b4e498da10cd4e3884fc95c97f2e2f74

ITU512 - Drug Targets, Indications, Patents ... Efficacy of ITU512 in Healthy Participants and Patients With Sickle Cell Disease. 100 Clinical Results associated with ITU512. Login to view more data. 100 ...

5. ctsearchsupport.org ctsearchsupport.org/clinical-trials/a-phase-i-ii-study-of-itu512-in-healthy-participants-and-patients-with-sickle-cell-disease

A drug, ITU512, to treat sickle cell disease (SCD ... ITU512 is a molecular glue degrader that targets WIZ, and increases HbF. You'll get: The clinical trial doctors will check your health for up to 4 months.

6. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/530895

A Phase I/II Study of ITU512 in Healthy Participants and ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary food effect of ITU512 as well as the fetal hemoglobin ...