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

Trial Summary

What is the purpose of this trial?

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 (HbF)-inducing capacity of ITU512. This will be the first evaluation of the potential therapeutic effect of ITU512 in healthy participants and patients with sickle cell disease (SCD).

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 ITU512 safe for humans?

The research on hydroxyurea (HU), which may be related to ITU512, shows it is generally safe for children and adults with sickle cell disease. Studies found that any side effects were mild, temporary, and reversible, with no life-threatening events reported. ^{1 2 3 4 5}

Eligibility Criteria

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.

I am a woman who can become pregnant.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical complications in severe pediatric sickle cell disease and the impact of hydroxyurea. [2022]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Hydroxyurea for sickle cell disease in children and for prevention of cerebrovascular events: the Belgian experience. [2022]

4. England pubmed.ncbi.nlm.nih.gov

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

5. United States 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. [2021]