Dersimelagon for Erythropoietic Protoporphyria

(INSPIRE Trial)

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

165 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug dersimelagon for treating erythropoietic protoporphyria?

Dersimelagon is being developed as a new drug for erythropoietic protoporphyria, and studies show it is rapidly absorbed and eliminated from the body, suggesting it is safe for continued development. It works by increasing skin eumelanin, which may help reduce sensitivity to light in people with this condition. ^{1 2 3 4 5}

Is dersimelagon safe for humans?

Dersimelagon has been tested in healthy volunteers and showed rapid absorption and elimination, with most of it being excreted through feces, suggesting it is not retained in the body. These studies support its continued development, indicating it is generally safe for human use. ^{1 2 3 4 6}

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 to help protect against light sensitivity. This is different from other treatments that may not target this specific receptor or mechanism. ^{1 2 3 4 6}

What is the purpose of this trial?

To investigate the efficacy of MT-7117 on time to onset and severity of first prodromal symptoms (burning, tingling, itching, or stinging) associated with sunlight exposure in adults and adolescents with EPP or XLP.

Research Team

Head of Medical Science

Principal Investigator

Mitsubishi Tanabe Pharma America Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 (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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Results from a first-in-human study of dersimelagon, an investigational oral selective MC1R agonist. [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. England pubmed.ncbi.nlm.nih.gov

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

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

Dersimelagon in Erythropoietic Protoporphyrias. [2023]

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

Afamelanotide for Erythropoietic Protoporphyria. [2018]

6. 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]