84 Participants Needed

NDec for Sickle Cell Disease

(ASCENT1 Trial)

Recruiting at 99 trial locations
NN
Overseen ByNovo Nordisk
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Novo Nordisk A/S
Must be taking: Hydroxyurea
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This trial tests a new medicine called NDec for people with sickle cell disease. NDec combines two drugs to help manage the disease. Participants will take capsules regularly over several months to see how well the medicine works and if it is safe.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but if you are taking Hydroxyurea (HU), you may continue it during the study. However, you cannot participate if you have taken voxelotor, crizanlizumab, or L-glutamine within 12 weeks before the trial or plan to take them during the trial.

What data supports the effectiveness of the drug NDec for treating sickle cell disease?

Research shows that decitabine, a component of NDec, can increase fetal hemoglobin levels in patients with sickle cell anemia, which helps reduce symptoms. In a study, patients who did not respond to another treatment (hydroxyurea) saw an increase in fetal hemoglobin and overall hemoglobin levels without significant side effects.12345

What makes the drug NDec unique for treating sickle cell disease?

NDec is unique because it combines decitabine with tetrahydrouridine to improve the oral availability of decitabine, which is usually broken down quickly in the body. This combination allows for a more effective and prolonged exposure to decitabine, potentially increasing fetal hemoglobin levels, which can be beneficial for sickle cell disease.678910

Research Team

CT

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

Adults over 18 with sickle cell disease (SCD), having had 2-10 pain episodes in the last year, and specific blood criteria can join. Excluded are those on chronic transfusions, recent other treatments for SCD, certain blood counts outside normal ranges, pregnant or breastfeeding women, and those not using effective contraception.

Inclusion Criteria

Reticulocyte count above upper limit of the normal (ULN) at visit 1
I have had 2-10 painful episodes related to my condition in the last year.
My weight is between 40 and 125 kg.
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Exclusion Criteria

I am a male willing to use a condom, and my partner uses effective birth control during the trial and for up to 12 months after.
Platelet count greater than 800 x 10^9/L at visit 1
I haven't taken voxelotor, crizanlizumab, or L-glutamine in the last 12 weeks.
See 6 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NDec, NDec and placebo, or placebo. Participants on HU may continue HU or receive NDec treatments.

24 weeks
Twice weekly capsule administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 weeks

Treatment Details

Interventions

  • NDec
Trial OverviewThe trial is testing NDec—a new oral medication combining decitabine-tetrahydrouridine—against a placebo and Hydroxyurea (HU) in people with SCD. Participants will be randomly assigned to receive either NDec capsules twice weekly or continue HU/placebo for about a year.
Participant Groups
6Treatment groups
Experimental Treatment
Active Control
Placebo Group
Group I: HU-non-eligible - NDec plus placeboExperimental Treatment2 Interventions
HU-non eligible patients randomised to treatment with NDec on one day and placebo on the other day
Group II: HU-non-eligible - NDec plus NDecExperimental Treatment1 Intervention
HU-non eligible patients randomised to treatment with NDec on both days
Group III: HU-active - NDec plus placeboExperimental Treatment2 Interventions
HU-active patients randomised to treatment with NDec on one day and placebo on the other day
Group IV: HU-active - NDec plus NDecExperimental Treatment1 Intervention
HU-active patients randomised to treatment with NDec on both days
Group V: HU-active - HUActive Control1 Intervention
HU-active patients randomised to continue on open-label HU treatment
Group VI: HU-non-eligible - Placebo plus placeboPlacebo Group1 Intervention
HU-non eligible patients randomised to treatment with placebo on both days

Find a Clinic Near You

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials
1,578
Recruited
3,813,000+
Lars Fruergaard Jørgensen profile image

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange profile image

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Findings from Research

In a 9-month study involving 7 patients with sickle cell anemia, repeated dosing of decitabine significantly increased fetal hemoglobin (HbF) levels from a pretreatment average of 3.12% to a maximum of 18.35%, indicating its efficacy in patients who did not respond to hydroxyurea.
Decitabine was well-tolerated, with no cases of neutropenia or cumulative toxicity observed, suggesting that shorter treatment intervals could be possible, potentially leading to even greater improvements in hemoglobin levels.
Maintenance of elevated fetal hemoglobin levels by decitabine during dose interval treatment of sickle cell anemia.DeSimone, J., Koshy, M., Dorn, L., et al.[2021]
A study of 142 children with sickle cell disease showed that a lower initial dose of hydroxyurea (10-12 mg/kg/day) was effective in reducing hospital admissions due to vaso-occlusive crises, similar to higher doses (15-35 mg/kg/day).
Both low and high-dose groups experienced significant clinical improvements in laboratory markers and tolerated the treatment well, indicating that a cautious low-dose regimen is a safe and effective option for managing sickle cell disease.
Optimizing Hydroxyurea use in children with sickle cell disease: low dose regimen is effective.Sharef, SW., Al-Hajri, M., Beshlawi, I., et al.[2022]
In a study of 14 young children with sickle cell anemia, hydroxyurea was well-tolerated at a mean maximum tolerated dose of 28 mg/kg/day, showing significant improvements in laboratory parameters like hemoglobin and MCV over an average of 25 months.
Importantly, hydroxyurea treatment did not lead to any significant decline in kidney function or brain health, as indicated by stable transcranial Doppler velocities and no development of brain ischemic lesions, suggesting it may help prevent chronic organ damage in these children.
A pilot study of hydroxyurea to prevent chronic organ damage in young children with sickle cell anemia.Thornburg, CD., Dixon, N., Burgett, S., et al.[2021]

References

Maintenance of elevated fetal hemoglobin levels by decitabine during dose interval treatment of sickle cell anemia. [2021]
Optimizing Hydroxyurea use in children with sickle cell disease: low dose regimen is effective. [2022]
A pilot study of hydroxyurea to prevent chronic organ damage in young children with sickle cell anemia. [2021]
Pharmacokinetics and pharmacodynamics of an oral formulation of decitabine and tetrahydrouridine. [2023]
Hydroxyurea therapy for children with sickle cell disease: describing how caregivers make this decision. [2022]
In Vitro Interaction of Tetrahydrouridine with Key Human Nucleoside Transporters. [2023]
Subchronic oral toxicity study of decitabine in combination with tetrahydrouridine in CD-1 mice. [2021]
In vitro drug-drug interactions of decitabine and tetrahydrouridine involving drug transporters and drug metabolising enzymes. [2022]
Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
Effects of tetrahydrouridine on pharmacokinetics and pharmacodynamics of oral decitabine. [2022]