Oral Dersimelagon for Erythropoietic Protoporphyria

Recruiting at 59 trial locations

Overseen By Clinical Trials Information Desk, To prevent mis-communication,

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Mitsubishi Tanabe Pharma Development America, Inc.

Must not be taking: Opioids, Ketamine, Cannabis, others

Disqualifiers: Melanoma, Renal disease, Psychiatric disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 66 months

301 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a pill called dersimelagon to see if it is safe and tolerable for patients who need long-term treatment.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. You must not use phototherapy, afamelanotide, cimetidine, or certain antioxidant agents within 3 to 4 weeks before starting. Additionally, you should avoid drugs metabolized by specific enzymes or proteins within 1 week before starting.

How is the drug dersimelagon different from other treatments for erythropoietic protoporphyria?

Dersimelagon is unique because it is an oral drug that works by selectively activating the melanocortin 1 receptor, which increases skin eumelanin levels, potentially reducing sensitivity to light. This mechanism is different from other treatments, and its oral administration makes it more convenient compared to other options. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Dersimelagon for treating Erythropoietic Protoporphyria?

Dersimelagon is being developed as a new oral drug for Erythropoietic Protoporphyria, and studies show it increases skin eumelanin, which may help reduce sensitivity to light. It is rapidly absorbed and eliminated from the body, supporting its potential as a treatment for photosensitive conditions. ^{1 2 3 4 5}

Research Team

Head of Medical Science

Principal Investigator

Mitsubishi Tanabe Pharma America Inc.

Eligibility Criteria

This trial is for individuals with Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP), weighing at least 30 kg, able to travel for visits, and not pregnant. They must have completed a previous MT-7117 study and agree to use two effective contraception methods if of childbearing potential.

Inclusion Criteria

I am not breastfeeding and have a negative pregnancy test.

Subjects who complete MT-7117-G01 (complete through Week 58 [Visit 12])

I am a woman, not breastfeeding, and my pregnancy test before starting the study drug was negative.

Exclusion Criteria

Your liver tests show high levels of AST, ALT, ALP, or bilirubin.

I have had melanoma in the past.

I have melanoma or lesions that might be melanoma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral dersimelagon to evaluate long-term safety and tolerability

66 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive oral dersimelagon to assess long-term safety and tolerability

66 months

Treatment Details

Interventions

• MT-7117

Trial Overview The trial is testing the long-term safety and tolerability of an oral medication called Dersimelagon (MT-7117) in patients with EPP or XLP who have previously participated in the initial MT-7117-G01 study.

Participant Groups

Group I: Dersimelagon 200mg Experimental Treatment 1 Intervention

MT-7117 is already approved in European Union, United States for the following indications:

Approved in European Union as Dersimelagon for:

• Erythropoietic Protoporphyria (EPP)
• X-Linked Protoporphyria (XLP)

Approved in United States as Dersimelagon for:

• Erythropoietic Protoporphyria (EPP)
• X-Linked Protoporphyria (XLP)

Who Is Running the Clinical Trial?

Mitsubishi Tanabe Pharma Development America, Inc.

Lead Sponsor

Trials

22

Recruited

2,600+

Mitsubishi Tanabe Pharma America Inc.

Lead Sponsor

Trials

27

Recruited

3,300+

Findings from Research

Dersimelagon, a new oral medication for conditions like erythropoietic protoporphyria, showed rapid absorption and a 97% relative oral bioavailability for the 100-mg tablets compared to the 50-mg tablets in a study involving 50 healthy participants.

The study found that while a high-fat meal did not affect the overall exposure of dersimelagon, it increased the peak concentration (Cmax) by 22%, indicating that food intake can influence the drug's absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Oral Bioavailability and Effect of Various Gastric Conditions on the Pharmacokinetics of Dersimelagon in Healthy Adult Volunteers. Ogawa, K., Ide, R., Belongie, K., et al.[2023]

Dersimelagon is a novel oral medication that shows rapid absorption and elimination in humans, with a median time to peak concentration of 2 hours, indicating efficient processing by the body.

The drug is primarily excreted through feces rather than urine, with negligible retention in the body, suggesting a favorable safety profile for continued development in treating conditions like erythropoietic protoporphyria and systemic sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorption, metabolism, and excretion of [14 C]dersimelagon, an investigational oral selective melanocortin 1 receptor agonist, in preclinical species and healthy volunteers. Tsuda, M., Ogawa, K., Endou, T., et al.[2023]

Dersimelagon, an investigational oral medication for erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP), was found to be generally well tolerated in a phase 1 study involving healthy participants, with common side effects including skin hyperpigmentation.

The pharmacokinetics of dersimelagon showed a consistent profile across different age and race groups, with significant increases in melanin density observed after multiple doses, suggesting potential efficacy that needs further exploration in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from a first-in-human study of dersimelagon, an investigational oral selective MC1R agonist. Ogasawara, A., Ogawa, K., Ide, R., et al.[2023]

In a phase 2 trial involving 102 patients with erythropoietic protoporphyria or X-linked protoporphyria, the melanocortin 1 receptor agonist dersimelagon significantly increased the time to the first symptoms associated with sunlight exposure, with improvements of 53.8 minutes at 100 mg and 62.5 minutes at 300 mg compared to placebo.

Dersimelagon also appeared to enhance quality of life for patients, although common side effects included nausea, freckles, headache, and skin hyperpigmentation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dersimelagon in Erythropoietic Protoporphyrias. Balwani, M., Bonkovsky, HL., Levy, C., et al.[2023]

Dersimelagon (MT-7117) is being evaluated as a new treatment for Erythropoietic protoporphyria (EPP) in a phase III clinical trial, which is currently ongoing in the US and Europe.

The authors argue that using a placebo in this trial is ethically questionable due to the existence of an approved treatment for EPP, suggesting that a noninferiority active-control trial would be a more appropriate design to assess the efficacy of dersimelagon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current trials in erythropoietic protoporphyria: are placebo controls ethical? Barman-Aksözen, J., Andreoletti, M., Blasimme, A.[2023]

References

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

The Oral Bioavailability and Effect of Various Gastric Conditions on the Pharmacokinetics of Dersimelagon in Healthy Adult Volunteers. [2023]

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

Absorption, metabolism, and excretion of [14 C]dersimelagon, an investigational oral selective melanocortin 1 receptor agonist, in preclinical species and healthy volunteers. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Results from a first-in-human study of dersimelagon, an investigational oral selective MC1R agonist. [2023]

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

Dersimelagon in Erythropoietic Protoporphyrias. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Current trials in erythropoietic protoporphyria: are placebo controls ethical? [2023]