Oral Carbon Monoxide Therapy for Sickle Cell Anemia

Recruiting at 2 trial locations

Overseen By Andrew Gomperts

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hillhurst Biopharmaceuticals, Inc.

Must be taking: Hydroxyurea

Must not be taking: Voxelotor, Crizanlizumab

Disqualifiers: Cardiac disease, Renal dysfunction, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

9 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an oral carbon monoxide therapy called HBI-002 for individuals with sickle cell disease. The goal is to determine the safety and bodily effects of this liquid treatment when taken daily for 14 days. It targets those who have experienced frequent pain episodes or complications such as chest syndrome or strokes due to sickle cell disease. This trial may suit non-smokers with sickle cell disease who haven't had recent severe pain episodes and are not using certain other medications. As a Phase 1, Phase 2 trial, the research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot use voxelotor, crizanlizumab, or any prescription drugs not for sickle cell disease within 7 days or 5 half-lives before starting. Herbal and vitamin supplements (except L-glutamine) must be stopped 14 days before. You can continue prescribed pain medications if the dose hasn't changed recently.

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

Research has shown that low levels of carbon monoxide (CO) in treatments like HBI-002 are not harmful, indicating they are generally safe for use. Studies have found that the CO levels in HBI-002 remain low enough to avoid negative effects. This is particularly important for individuals with sickle cell disease considering participation in a trial for this treatment.

In earlier studies with healthy adults, HBI-002 was well-tolerated, with most participants experiencing no serious side effects. Although the trial remains in its early stages, these findings suggest that HBI-002 is safe. However, like any treatment, potential side effects are monitored closely during the trial. ^{1 2 3 4 5}

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

Researchers are excited about HBI-002 for sickle cell anemia because it uses carbon monoxide, an unusual yet promising active ingredient. Unlike traditional treatments that typically focus on managing pain or preventing complications through blood transfusions and hydroxyurea, HBI-002 delivers carbon monoxide orally. This method could help reduce inflammation and oxidative stress, directly targeting the underlying causes of sickle cell crises. The potential for an oral liquid form makes it easier to administer compared to existing options, potentially improving patient compliance and quality of life.

What evidence suggests that this treatment might be an effective treatment for sickle cell anemia?

Research has shown that carbon monoxide (CO) might help treat sickle cell disease. In past studies, CO proved to be safe and well-tolerated in several clinical trials, including those involving people with sickle cell disease. In animal studies, HBI-002, a liquid form of CO taken orally, increased hemoglobin levels and red blood cell counts. These changes are important because they might reduce the painful episodes patients experience. Although more research with humans is needed, early results suggest that HBI-002, which participants in this trial will receive, could effectively manage sickle cell disease symptoms. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for non-smoking individuals aged 14-55 with sickle cell disease. Participants must have a stable weight and BMI, normal heart function, and no significant medical issues. Women must not be pregnant and all participants should agree to use effective contraception during the study.

Inclusion Criteria

You must agree to use a very effective form of birth control during the study and for 30 days after it ends, if needed.

Your carboxyhemoglobin level is 3.5% or lower before starting the study.

I am a man who will use a condom, and my partner will use another form of birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily doses of HBI-002, an oral carbon monoxide liquid, for 14 days

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HBI-002

Trial Overview The trial tests HBI-002, an oral liquid carbon monoxide treatment for sickle cell disease. Over two weeks, its safety, how well it's tolerated by patients' bodies (tolerability), how the body processes it (pharmacokinetics), and how it affects the disease (pharmacodynamics) are studied.

How Is the Trial Designed?

Group I: Ascending Multiple Dose Experimental Treatment 1 Intervention

Drug: HBI-002 (oral liquid carbon monoxide drug product)

Who Is Running the Clinical Trial?

Hillhurst Biopharmaceuticals, Inc.

Lead Sponsor

Trials

2

Recruited

30+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study involving sickle cell disease patients, administering carbon monoxide at concentrations of 1000-2000 ppm led to a significant prolongation of red blood cell survival, indicating a potential positive effect on the properties of sickle cells.

Despite these promising results, the authors do not recommend carbon monoxide as a treatment for sickle cell disease at this time, but suggest that further controlled trials could be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of carbon monoxide on red cell life span in sickle cell disease. Beutler, E.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06144749

Study Details | NCT06144749 | A Safety, Efficacy, and ... This is a multi-center, open label Phase 2a clinical trial in subjects with sickle cell disease to assess safety, tolerability, pharmacokinetics, and ...

2. reporter.nih.gov reporter.nih.gov/search/Xdu1b5a8jU6SuFtlB3KUCg/project-details/9555192

HBI-002 to Prevent Vaso-Occlusive Crises in Sickle Cell Disease The safety and tolerability of CO has been demonstrated in eight successfully completed Phase 1 and Phase 2 studies, including two Phase 1b studies in SCD ...

3. docwirenews.com docwirenews.com/post/first-patient-dosed-in-clinical-trial-of-novel-therapy-hbi-002-for-scd

First Patient Dosed in Clinical Trial of Novel Therapy HBI ... In a preclinical murine model, mice treated with HBI-002 showed an increase in hemoglobin levels, red blood cell counts, and hematocrits with a ...

4. respiratory-therapy.com respiratory-therapy.com/products-treatment/pharmaceuticals/clinical-trials/sickle-cell-disease-study-tests-liquid-carbon-monoxide/

Sickle Cell Disease Study Tests Liquid Carbon Monoxide | RT A Phase 2a clinical trial will evaluate an oral low-dose liquid carbon monoxide (CO) theray for the treatment of sickle cell disease.

5. ashpublications.org ashpublications.org/blood/article/143/24/2544/515438/An-oral-carbon-monoxide-releasing-molecule

An oral carbon monoxide–releasing molecule protects against ... An oral carbon monoxide–releasing molecule protects against acute hyperhemolysis in sickle cell disease

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03926819

A Study to Assess the Safety and Pharmacokinetics of HBI-002, ... This is a single center, open label Phase 1 clinical trial in normal adult subjects to assess safety, tolerability, pharmacokinetics, and pharmacodynamics ...