70 Participants Needed

FTX-6058 for Sickle Cell Disease

Recruiting at 22 trial locations
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Overseen ByCall Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called FTX-6058 for individuals with sickle cell disease. The study aims to assess the treatment's safety, tolerability, and how it moves through and works in the body. Participants will take varying doses to determine the optimal and safest amount. This trial may suit those with sickle cell disease who frequently experience pain crises or complications like acute chest syndrome and have not found success with other treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I need to stop my current medications to join the trial?

Yes, you will need to stop taking certain medications before joining the trial. Specifically, you must stop taking voxelotor and crizanlizumab at least 60 days before starting the study drug, and L-glutamine at least 24 hours before.

Is there any evidence suggesting that FTX-6058 is likely to be safe for humans?

Research shows that FTX-6058, the treatment under study, is generally safe. In earlier studies, participants tolerated this drug well, with no serious safety concerns reported.

The treatment, also known as Pociredir, is administered in varying doses to determine the optimal and safest amount for patients. So far, patients have responded well, indicating positive signs for its safety.

These results come from early-stage trials, which are specifically designed to assess the safety of a new treatment before wider use.12345

Why do researchers think this study treatment might be promising?

Researchers are excited about FTX-6058 for sickle cell disease because it represents a novel approach by potentially increasing fetal hemoglobin levels in patients, which can help alleviate the symptoms of the disease. Unlike traditional treatments like hydroxyurea, which primarily works by reducing the frequency of painful crises, FTX-6058 targets the underlying genetic issues causing sickle cell disease. This new mechanism of action could offer more comprehensive management of the condition and improve quality of life for patients by addressing the root cause rather than just the symptoms.

What evidence suggests that FTX-6058 might be an effective treatment for sickle cell disease?

Research has shown that FTX-6058, which participants in this trial may receive, may help treat sickle cell disease. In studies, patients experienced significant increases in fetal hemoglobin (HbF), which can reduce pain and improve blood health. For example, HbF levels increased from 7.6% to 16.2% over 12 weeks. Early research indicated that FTX-6058 could raise HbF levels to as much as 40% of total hemoglobin. Higher HbF levels are associated with fewer sickle cell complications, suggesting this treatment could be beneficial.12356

Who Is on the Research Team?

AA

Adeyemi Adenola, MD

Principal Investigator

Fulcrum Therapeutics

Are You a Good Fit for This Trial?

Adults aged 18-65 with sickle cell disease (SCD), specific genotypes, and low fetal hemoglobin can join. They must have had multiple SCD complications despite treatment with drugs like Hydroxyurea or be ineligible for chronic transfusions due to side effects.

Inclusion Criteria

Total Hb ≥ 5.5 g/dL and ≤ 12 g/dL (males) or ≤ 10.6 g/dL (females) at screening
Documented HbF ≤ 20% of total Hb
I've been on voxelotor, crizanlizumab, or L-glutamine for 6 months without improvement or couldn't tolerate them.
See 7 more

Exclusion Criteria

I needed medical care for a sickle cell complication within the last 14 days.
I do not have severe kidney disease or require dialysis.
I have had a bone marrow, stem cell, or gene therapy.
See 3 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pociredir for 12 weeks with varying doses across cohorts

12 weeks
Visits on Days 1, 14, 28, 42, 56, 70, 84

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks
Visits on Days 88, 91, and 112

What Are the Treatments Tested in This Trial?

Interventions

  • FTX-6058
Trial Overview The trial is testing FTX-6058 oral capsules to see if they're safe and how they affect the body in people with SCD. It looks at how the drug moves through and out of the body, as well as its impact on disease factors.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Pociredir oral capsule(s) in Sickle Cell participantsExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Fulcrum Therapeutics

Lead Sponsor

Trials
8
Recruited
680+
Headquarters
Cambridge, United States

Published Research Related to This Trial

In a study of 38 Kuwaiti children with steady-state sickle cell disease (SCD), plasma levels of TNF-alpha were undetectable, suggesting low systemic inflammation in these patients.
However, when their immune cells were activated, the sickle cell patients showed significantly higher TNF-alpha responses compared to controls, indicating a heightened inflammatory response upon stimulation despite the absence of detectable levels in their plasma.
Tumor necrosis factor-alpha is undetectable in the plasma of SS patients with elevated Hb F.Raghupathy, R., Haider, MZ., Azizieh, F., et al.[2019]
In a double-blind randomized controlled trial involving patients with sickle cell anemia, treatment with hydroxyurea (HU) reduced the median frequency of painful crises by nearly 50% compared to placebo, indicating its efficacy in managing the disease.
The study found that lower neutrophil counts were strongly associated with reduced crisis rates, suggesting that HU may work by decreasing inflammation and improving blood flow, although the exact mechanism of action remains unclear.
Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive "switching" agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia.Charache, S., Barton, FB., Moore, RD., et al.[2022]
The BCH-BB694 lentiviral vector effectively reactivates fetal hemoglobin production while reducing harmful adult sickle hemoglobin in sickle cell disease, showing a 3- to 5-fold increase in fetal hemoglobin levels in transduced cells.
Preclinical studies indicate that BCH-BB694 is non-toxic and can be produced at a clinically relevant scale, supporting its potential for safe and effective use in human trials for treating sickle cell disease.
Preclinical Evaluation of a Novel Lentiviral Vector Driving Lineage-Specific BCL11A Knockdown for Sickle Cell Gene Therapy.Brendel, C., Negre, O., Rothe, M., et al.[2020]

Citations

Fulcrum Therapeutics Announces Results from the 12 mg ...“These data, showing clinically-meaningful increases in HbF levels, reductions in pain crises, and improvements in markers of hemolysis, are ...
NCT05169580 | Safety, Tolerability, Pharmacokinetics and ...This is a study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of Pociredir in participants with sickle cell disease. Detailed ...
Clinical Pipeline of FTX-6058 for Sickle Cell DiseaseConsistent with previous results, FTX-6058 led to HbF induction of 8.6%, an increase from 7.6% at baseline to 16.2% at 12 weeks. Seven of 16 ...
P1472: INTERIM RESULTS OF SAFETY, TOLERABILITY ...Preclinically, FTX-6058 has demonstrated increases in HbF levels up to approximately 40% of total hemoglobin, which has the potential to positively impact ...
Trial of Pociredir for SCD completes enrollment of high- ...A Phase 1b clinical trial testing pociredir in adults with sickle cell disease has completed enrollment of its high-dose group.
Interim Results of a Phase 1b Study (PIONEER) of an Oral ...It was generally well tolerated, with no serious drug related safety issues. Aim of this study is to assess the safety, tolerability, ...
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