Oral Carbon Monoxide Therapy for Sickle Cell Anemia

Overseen By Andrew Gomperts

Age: < 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

8 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multi-center, open label Phase 2a clinical trial in subjects with sickle cell disease to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of HBI-002, an orally administered liquid containing carbon monoxide (CO), with doses daily for 14 days.

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.

What data supports the effectiveness of the treatment HBI-002 for sickle cell anemia?

Research shows that oral carbon monoxide therapy, like HBI-002, can help reduce inflammation and improve blood health in sickle cell disease. In mouse studies, HBI-002 increased hemoglobin levels and reduced white blood cell counts, suggesting it may help manage symptoms of sickle cell anemia. ^{1 2 3 4 5}

Is oral carbon monoxide therapy safe for humans?

Research on oral carbon monoxide therapy, specifically HBI-002, in mice shows it can be administered safely at low concentrations, with beneficial effects on inflammation and blood health. However, more studies are needed to confirm its safety in humans. ^{1 2 3 5 6}

How is the drug HBI-002 unique in treating sickle cell anemia?

HBI-002 is unique because it delivers carbon monoxide (CO) orally in a liquid form, which helps reduce inflammation and improve blood flow in sickle cell anemia. Unlike other treatments, it avoids the complications of inhaling CO and allows for easier self-administration. ^{1 2 3 4 5}

Eligibility Criteria

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

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

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

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

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

The role of carbon monoxide and heme oxygenase in the prevention of sickle cell disease vaso-occlusive crises. [2019]

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

Oral carbon monoxide therapy in murine sickle cell disease: Beneficial effects on vaso-occlusion, inflammation and anemia. [2019]

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

Carboxyhemoglobin levels in patients with sickle-cell anemia: relationship to hemolytic and vasoocclusive severity. [2019]

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

Inhaled carbon monoxide reduces leukocytosis in a murine model of sickle cell disease. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Hemoglobin-Based Blood Substitutes and the Treatment of Sickle Cell Disease: More Harm than Help? [2018]