What side effects are associated with this type of intervention?

Common treatments for Polycythemia Vera include hydroxyurea, ruxolitinib, and interferon alfa. Hydroxyurea can cause cytopenias, mucocutaneous ulcers, diarrhea, peripheral neuropathy, and potential teratogenicity. Ruxolitinib's side effects include cytopenias, dizziness, headache, fatigue, bruising, elevated serum cholesterol, and increased risk of infections. Interferon alfa may lead to flu-like symptoms, fatigue, depression, and liver enzyme abnormalities. For LSD1 inhibitors like Bomedemstat, specific side effects are not detailed, but they are generally expected to be tolerable based on the study's hypothesis.

What prior FDA approvals exist?

The FDA has approved several treatments for Polycythemia Vera, including hydroxyurea, which is commonly used to reduce blood cell production, and ruxolitinib, a JAK1/JAK2 inhibitor that helps control blood counts and reduce spleen size. While Bomedemstat, an LSD1 inhibitor, is currently being studied for its potential benefits in PV, there are no prior FDA approvals specifically for LSD1 inhibitors in the treatment of PV. The focus remains on managing symptoms and reducing the risk of complications through existing approved therapies.

What other types of research exist?

Promising novel alternatives to Bomedemstat for Polycythemia Vera patients include ruxolitinib, a Janus kinase (JAK) inhibitor, which has shown efficacy in reducing hematocrit levels and spleen size, and fedratinib, another JAK inhibitor that has been effective in patients resistant to or intolerant of ruxolitinib. Both treatments are already approved for myeloproliferative disorders and have demonstrated significant clinical benefits.

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LSD1 Inhibitor

Bomedemstat for Polycythemia Vera

Q: What is the mechanism of action of this treatment?

Polycythemia Vera (PV) is commonly treated with agents that target the underlying pathophysiology of the disease, such as JAK2 inhibitors and LSD1 inhibitors. Bomedemstat, an LSD1 inhibitor, works by inhibiting lysine-specific demethylase 1, which plays a role in the regulation of gene expression involved in hematopoiesis. This inhibition can lead to a reduction in the overproduction of red blood cells, which is a hallmark of PV. Other treatments, like hydroxyurea, reduce blood cell production by inhibiting DNA synthesis, while JAK2 inhibitors, such as ruxolitinib, target the JAK-STAT pathway to control cell proliferation. These mechanisms are crucial for PV patients as they help manage symptoms, reduce the risk of complications like thrombosis, and improve overall quality of life.

Phase 2

Waitlist Available

Research Sponsored by Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to ~56 weeks

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a pill called bomedemstat for patients with polycythemia vera, a condition with too many red blood cells. The pill works by blocking an enzyme to reduce red blood cells and improve symptoms like an enlarged spleen.

Who is the study for?

This trial is for people with Polycythemia Vera who haven't responded well to at least one standard treatment. They should have a certain level of platelets and white blood cells, expect to live more than 36 weeks, and meet specific diagnostic criteria. Those with severe physical limitations, unresolved side effects from past treatments, certain infections or bleeding risks, pregnant or breastfeeding women, or on prohibited meds can't join.

What is being tested?

The study tests Bomedemstat (MK-3543), an oral drug that targets LSD1 enzymes in patients with Polycythemia Vera. The goal is to see if it's safe and can manage the disease by reducing blood counts, improving symptoms, and shrinking enlarged spleens within 36 weeks.

What are the potential side effects?

While the exact side effects are not listed here, typical reactions may include issues related to digestion due to oral intake of medication; potential impact on blood counts since it targets hematologic response; fatigue as commonly seen in such treatments; and possibly liver enzyme changes given its metabolic pathway.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to ~56 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to ~56 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to ~56 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of participants who discontinued study intervention due to AEs

Number of participants with adverse events (AEs)

Number of participants with sustained change from baseline of hematocrit to <45% without concomitant phlebotomy at Week 36

Secondary study objectives

Duration of platelet count ≤ 450 x 10^9/L in participants at Week 36

Duration of reduction of hematocrit to <45% without phlebotomy

Duration of white blood cell (WBC) count <10 x 10^9/L in participants at Week 36

+6 more

Side effects data

From 2022 Phase 1 & 2 trial • 90 Patients • NCT03136185

55%

Thrombocytopenia

36%

Contusion

27%

Arthralgia

27%

Dysgeusia

27%

Back pain

27%

Nausea

27%

Anaemia

27%

Depression

27%

Constipation

27%

Oedema peripheral

27%

Hypocalcaemia

18%

Activated partial thromboplastin time prolonged

18%

Palpitations

18%

Dyspnoea

18%

Hyperuricaemia

18%

Fatigue

18%

Hyponatraemia

18%

Cough

18%

Fall

18%

Lymphopenia

18%

Blood uric acid increased

18%

Insomnia

18%

Dizziness

18%

Muscular weakness

18%

Pruritus

18%

Abdominal pain

18%

Diarrhoea

18%

Alopecia

18%

Pain in extremity

18%

Asthenia

18%

Decreased appetite

18%

Hypertension

18%

International normalised ratio increased

18%

Dry mouth

18%

Urine abnormality

Neutropenia

Neuralgia

Drooling

Dysphagia

Skin ulcer

Confusional state

Hypotension

Headache

Neck pain

Blood bilirubin increased

Blood magnesium decreased

Chest pain

Wound secretion

Petechiae

Hyperglycaemia

Non-cardiac chest pain

Cellulitis

Stress cardiomyopathy

Myalgia

Balance disorder

Sinus tachycardia

Sepsis

Musculoskeletal chest pain

Blood lactate dehydrogenase increased

Eye oedema

Blood creatinine increased

Splenic infarction

Epistaxis

Vomiting

Catathrenia

Traumatic haematoma

Leukopenia

Rash

Hypokalaemia

Breast pain

Pelvic pain

Anal pruritus

Myocardial ischaemia

Hypophosphataemia

Mouth haemorrhage

Blood albumin decreased

Urinary incontinence

Vulvovaginal pruritus

Pneumonitis

Pallor

Disturbance in attention

Hyperhidrosis

Eczema

Abdominal distension

Bone pain

Blood thyroid stimulating hormone increased

Flank pain

Hyperactive pharyngeal reflex

Heart rate irregular

Cachexia

Nail disorder

Stomatitis

Pyrexia

Abdominal pain upper

Rash maculo-papular

Haematoma

Early satiety

Calcium ionised decreased

Gout

Dry skin

Pleural effusion

Lacrimation increased

Flatulence

Aortic arteriosclerosis

Blood alkaline phosphatase increased

Abdominal wall haematoma

Hypervolaemia

100%

80%

60%

40%

20%

Study treatment Arm

Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d

Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d

Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d

Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d

Ph 2b PMF: Bomedemstat 0.5 mg/kg/d

Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d

Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d

Ph 2b PMF: Bomedemstat 0.6 mg/kg/d

Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: BomedemstatExperimental Treatment1 Intervention

Participants will receive bomedemstat daily for 36 weeks and may qualify for additional treatment through Week 52 if deriving clinical benefit.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bomedemstat

2021

Completed Phase 2

~250

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Polycythemia Vera (PV) is commonly treated with agents that target the underlying pathophysiology of the disease, such as JAK2 inhibitors and LSD1 inhibitors. Bomedemstat, an LSD1 inhibitor, works by inhibiting lysine-specific demethylase 1, which plays a role in the regulation of gene expression involved in hematopoiesis. This inhibition can lead to a reduction in the overproduction of red blood cells, which is a hallmark of PV. Other treatments, like hydroxyurea, reduce blood cell production by inhibiting DNA synthesis, while JAK2 inhibitors, such as ruxolitinib, target the JAK-STAT pathway to control cell proliferation. These mechanisms are crucial for PV patients as they help manage symptoms, reduce the risk of complications like thrombosis, and improve overall quality of life.