Dersimelagon for Erythropoietic Protoporphyria

(INSPIRE Trial)

Not currently recruiting at 36 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 America Inc.

Must not be taking: Afamelanotide, Cimetidine, Antioxidants, Opioids

Disqualifiers: Photodermatoses, Hepatobiliary disease, Melanoma, others

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: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called MT-7117 (Dersimelagon) for individuals with Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP). These conditions cause painful reactions to sunlight, such as burning, tingling, itching, or stinging sensations. The study will compare MT-7117 to a placebo to determine if it can delay or reduce these symptoms. Individuals with a confirmed diagnosis of EPP or XLP who experience sunlight-induced symptoms may be suitable for this trial. Participants must be willing to spend time in the sun and travel to study sites. As a Phase 3 trial, this study is the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before joining. You must stop taking afamelanotide, phototherapy, cimetidine, certain antioxidants, and chronic scheduled pain medications like opioids within specific timeframes before starting the trial.

Is there any evidence suggesting that MT-7117 is likely to be safe for humans?

Research shows that dersimelagon, also known as MT-7117, has been tested for safety in people with erythropoietic protoporphyria (EPP). In earlier studies, participants generally tolerated dersimelagon well, experiencing only mild to moderate side effects. Serious side effects were rare.

Researchers tested the treatment in a study comparing it to a placebo (a harmless pill with no real effect). This type of study helps clarify the treatment's actual effects. The results suggested that dersimelagon is safe enough for further research and development.

For those considering joining a trial, it is reassuring that dersimelagon has been well-tolerated in past tests. Always consult a doctor to determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for EPP?

Dersimelagon, known as MT-7117, is unique because it offers a new approach for treating erythropoietic protoporphyria (EPP). While traditional treatments like beta-carotene and narrowband UVB therapy aim to manage symptoms by increasing skin tolerance to light, Dersimelagon works differently by targeting the melanocortin-1 receptor, which can help boost melanin production in the skin. This mechanism could potentially provide a more effective way to reduce the painful reactions to sunlight that EPP patients experience. Researchers are excited about Dersimelagon because it represents a promising option that might improve the quality of life for individuals dealing with this condition.

What evidence suggests that MT-7117 might be an effective treatment for EPP?

Research has shown that dersimelagon, also known as MT-7117, may help treat erythropoietic protoporphyria (EPP). In this trial, participants will receive either dersimelagon or a placebo. Studies have found that dersimelagon can allow people to stay in sunlight longer without experiencing symptoms like burning or itching. In a recent study, patients taking dersimelagon could remain in the sun longer before feeling any discomfort. Early results suggest it can help manage EPP symptoms, improving life for those with this condition. Overall, the evidence supports its potential as an effective treatment for reducing sunlight sensitivity in people with EPP. ^{1 2 3 6 7}

Who Is on the Research Team?

Head of Medical Science

Principal Investigator

Mitsubishi Tanabe Pharma America Inc.

Are You a Good Fit for This Trial?

This trial is for adults and adolescents aged 12-75 with Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP). Participants must not be pregnant, should agree to use two forms of contraception, and be willing to expose themselves to sunlight. They cannot have certain liver conditions, drug abuse history, other skin diseases besides EPP/XLP, or be on conflicting medications.

Inclusion Criteria

I understand the study, its risks, and am willing to follow all requirements.

I am not breastfeeding and have a negative pregnancy test.

I can travel to the study location for all my appointments.

Exclusion Criteria

Subjects who participated in any previous MT-7117 clinical studies.

I have had melanoma in the past.

I have or had significant liver disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MT-7117 or placebo to evaluate efficacy on sunlight-induced symptoms over a 16-week period

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MT-7117

Trial Overview The trial tests Dersimelagon's effectiveness against a placebo in delaying the onset and reducing the severity of symptoms like burning or itching caused by sun exposure in people with EPP/XLP. It involves direct sunlight exposure as part of the study.

How Is the Trial Designed?

Group I: MT-7117 Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 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 America Inc.

Lead Sponsor

Trials

27

Recruited

3,300+

Published Research Related to This Trial

In two multicenter trials involving 168 patients, afamelanotide significantly increased the duration of pain-free sun exposure compared to placebo, with median times of 69.4 hours vs. 40.8 hours in the U.S. study and 6.0 hours vs. 0.8 hours in the EU study.

Afamelanotide also reduced the number of phototoxic reactions and improved quality of life, with a favorable safety profile where most adverse events were mild and serious events were not linked to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Afamelanotide for Erythropoietic Protoporphyria. Langendonk, JG., Balwani, M., Anderson, KE., et al.[2018]

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, 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 (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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2208754

Dersimelagon in Erythropoietic Protoporphyrias Results from this phase 2 trial support the effectiveness and safety of dersimelagon and its further development as a potential oral treatment ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03520036

NCT03520036 | Study to Evaluate Efficacy, Safety, and ... The purpose of this study is to investigate the efficacy and safety of MT-7117 on sunlight exposure duration without symptoms and tolerance in subjects with EPP ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10229459/

Results from a first-in-human study of dersimelagon, an ... ... protoporphyria: phase 2 clinical trial results evaluating the safety and effectiveness of dersimelagon (MT-7117), an oral MC1R agonist.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04402489

NCT04402489 | Study to Evaluate Efficacy, Safety, and ... The primary objective of this study is to investigate the efficacy of MT-7117 on time to onset and severity of first prodromal symptoms (burning, tingling, ...

5. ashpublications.org ashpublications.org/blood/article/136/Supplement%201/51/472215/Erythropoietic-Protoporphyria-Phase-2-Clinical

Erythropoietic Protoporphyria: Phase 2 Clinical Trial Results ... The oral, MC1R agonist dersimelagon was efficacious after 16 weeks of treatment in increasing symptom-free light exposure in patients with EPP or XLP at doses ...

6. mt-pharma-america.com mt-pharma-america.com/media/press-releases/2024/first-patient-enrolled-in-mtpa-inspire-study-of-investigational-dersimelagon-for-epp-and-xlp

First Patient Enrolled in MTPA INSPIRE Study ... INSPIRE is a phase 3 clinical study investigating the efficacy, safety, and tolerability of dersimelagon (MT-7117), in adults and adolescents ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37060458/

Results from a first-in-human study of dersimelagon, an ... Purpose: To describe outcomes from the first-in-human study of dersimelagon, an investigational oral selective MC1R agonist, under development ...