Combination Therapy for Sickle Cell Disease

Overseen By Lani Krauz

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: EpiDestiny, Inc.

Must be taking: Hydroxyurea

Must not be taking: Anti-seizure, L-glutamine

Disqualifiers: Pregnancy, Sepsis, Malignancy, HIV, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test new treatment combinations for people with sickle cell disease (SCD). Researchers seek to determine the effectiveness of nicotinamide (also known as niacinamide or Vitamin B3), used alone or with THU-decitabine, in managing SCD symptoms. Participants should have SCD and experience frequent pain episodes despite treatment with hydroxyurea, or they may choose not to take hydroxyurea. This study could offer new hope for those with difficult-to-manage sickle cell symptoms. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you must not have taken hydroxyurea in the last 4 weeks or l-glutamine in the last 28 days. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that nicotinamide is under investigation for its potential to treat sickle cell disease. Previous studies have found it safe, although some patients experienced higher liver enzyme levels, indicating liver stress. This occurred with doses higher than those used in the trial.

For THU-decitabine, research has found it safe for sickle cell disease patients. It targets specific enzymes to increase fetal hemoglobin, which can improve symptoms. No major safety concerns have been reported, and studies suggest it does not significantly affect other medications.

Both treatments appear well-tolerated based on previous studies, but discussing any concerns with the trial team is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for sickle cell disease because they offer new ways to tackle the condition. Unlike current treatments that often focus on managing symptoms, Nicotinamide is being explored for its potential to improve red blood cell health by enhancing their oxygen-carrying capacity. On the other hand, the combination of THU and decitabine targets the genetic underpinnings of the disease, which could lead to more effective long-term management. These innovative approaches could provide more comprehensive benefits for patients, aiming not just to relieve symptoms but to address the underlying causes of sickle cell disease.

What evidence suggests that this trial's treatments could be effective for sickle cell disease?

Research has shown that nicotinamide, a type of vitamin B, may help treat sickle cell disease. Some studies found it increased hemoglobin levels by more than 1 g/dL in 51% of patients, suggesting it might improve blood health in those with sickle cell disease. In this trial, some participants will receive nicotinamide.

THU-decitabine works differently by targeting the DNA changes that cause sickle cell disease. Research indicates it can help patients who don't respond to usual treatments, potentially relieving symptoms of the disease. Other participants in this trial will receive THU-decitabine. Both treatments are under further study to understand their effectiveness. ^{1 2 4 6 7}

Who Is on the Research Team?

Robert Molokie

Principal Investigator

University of Illinois at Chicago College of Medicine

Are You a Good Fit for This Trial?

Adults over 18 with confirmed sickle cell disease, symptomatic despite hydroxyurea treatment or refusing it. They must be stable (no recent acute SCD complications), weigh at least 40kg, and comply with care. Excluded are those unable to consent, pregnant/breastfeeding women, individuals with certain organ dysfunctions or severe concurrent diseases, drug/alcohol abusers within a year, and anyone on other experimental drugs recently.

Inclusion Criteria

I haven't had any severe sickle cell complications or hospital visits in the last 2 weeks.

I weigh at least 40kg.

I have consistently followed my treatment and care plan.

Exclusion Criteria

Platelet count >800 x 109/L

I am a man who will not use a condom during sex with a woman who can have children, even though I am asked to do so for 4 weeks after my last treatment.

You have used illegal drugs or abused alcohol in the past year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment with either oral THU-decitabine or nicotinamide for 12 weeks, followed by a combination of both for another 12 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may opt into an extension phase of combination treatment for an additional 24 weeks

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotinamide

Trial Overview The trial is testing the effectiveness of nicotinamide alone and in combination with oral THU-decitabine in treating high-risk sickle cell disease. It's a randomized control study involving 20 subjects who will receive either one of the treatments or both together.

How Is the Trial Designed?

Group I: THU Decitabine Experimental Treatment 1 Intervention

Oral 250 mg THU and 5 mg decitabine Once per week

Group II: Nicotinamide Experimental Treatment 1 Intervention

Oral Nicotinamide 1000 mg twice daily

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

Approved in United States as Nicotinamide for:

• Pellagra
• Acne vulgaris
• Rosacea
• Hyperpigmentation
• Hair thinning

Approved in European Union as Nicotinamide for:

• Pellagra
• Acne vulgaris
• Rosacea
• Hyperpigmentation
• Hair thinning

Who Is Running the Clinical Trial?

EpiDestiny, Inc.

Lead Sponsor

Trials

4

Recruited

90+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9578011/

Vitamin B supplementation for sickle cell disease - PMC To assess the effectiveness of vitamin B supplementation in children and adults with sickle cell disease (SCD), compared to no intervention or an alternative ...

2. clinicaltrials.eu clinicaltrials.eu/inn/nicotinamide/

Nicotinamide – Application in Therapy and Current Clinical ... Sickle cell disease: A study is exploring the potential of nicotinamide, alone or in combination with other drugs, in treating sickle cell disease.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6717594/

Targeting sickle cell disease root-cause pathophysiology ... A hemoglobin response, defined as an increase from baseline of >1 g/dL at week 24, occurred in 51% of the patients on the 1500 mg dose, 33% on the 900 mg dose, ...

4. researchgate.net researchgate.net/publication/364408594_Vitamin_B_supplementation_for_sickle_cell_disease

(PDF) Vitamin B supplementation for sickle cell disease we will present results using the RR with 95% CIs. Continuous data. For continuous outcomes (i.e. hematocrit, hemoglobin, mean. corpuscular ...

5. scinfo.org scinfo.org/2018/08/02/sickle-cell-news-for-august-2018/

Sickle Cell News for August 2018 “Endari, is the first approved treatment for sickle cell disease in pediatric patients 5 years of age and older and the first in nearly 20 years ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05789355

Effect of NUV001 Supplementation in Patients Suffering ... This is a pilot study of daily dosing of NUV001 as a dietary supplement in 12 sickle cell disease patients with 3 months of follow-up plus 1 month after ...

7. aboutnad.com aboutnad.com/blogs/blog/what-the-science-says-about-b3-vitamins-and-methylation

What the Science Says About B3 Vitamins and Methylation Another measured increased ALT and AST levels in sickle cell anemia patients taking 1.5 grams of niacin per day for 12 weeks [13]. A head-to-head study compared ...