MDI-2517 for Safety and Tolerability

Overseen By Jessica Reed, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: MDI Therapeutics, Inc.

Must not be taking: NSAIDs, SSRIs, others

Disqualifiers: Major illness, Infections, Drug abuse, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment called MDI-2517 to assess its safety and effects on the body. It targets healthy volunteers without recent major illnesses. Participants will receive either a single dose of MDI-2517 or a placebo to compare outcomes. Those who are generally healthy and free of major medical conditions may find this trial suitable. As a Phase 1 trial, participants will be among the first to help researchers understand how this new treatment works in people.

Do I have to stop taking my current medications for the trial?

Yes, you must stop taking prescription or nonprescription drugs, including vitamins, herbal and dietary supplements, within 7 days or 5 half-lives before the first dose of the study drug.

Is there any evidence suggesting that MDI-2517 is likely to be safe for humans?

Research shows that MDI-2517 remains in the early testing stages, providing limited information about its safety. As a Phase 1 study, this marks the first time MDI-2517 is tested in humans. The main goal is to assess the treatment's safety and tolerability in healthy volunteers.

The focus is on identifying possible side effects and understanding the body's reaction to the treatment. Although solid safety results are not yet available, this phase is crucial for identifying immediate concerns. If the FDA had approved MDI-2517 for other uses, it would suggest some level of safety; however, since it has not, the safety profile is still under evaluation.

Overall, researchers are carefully studying the safety of MDI-2517 in humans. Participants in this trial will provide important information about how the treatment works and potential side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

MDI-2517 is unique because it potentially offers a new way to address conditions that current treatments might not fully tackle. Unlike standard therapies that typically target symptoms indirectly, MDI-2517 works with a novel active ingredient designed to directly influence the underlying mechanisms of the condition. This could mean more effective symptom relief and possibly even faster results. Researchers are excited because this approach may lead to improved outcomes and offer new hope for patients who haven't responded well to existing treatments.

What evidence suggests that MDI-2517 could be effective?

A previous study tested MDI-2517 on healthy volunteers to observe its effects. This experimental drug aims to block certain actions in the body, potentially leading to beneficial outcomes. The current trial focuses on its safety and tolerability through various treatment arms with different single ascending doses. Early tests suggest it could be effective based on its interactions at a molecular level. Although limited data exists on its efficacy in humans, its mechanism shows promising potential for future treatments. Further research will be necessary to confirm these early findings. ^{1 2 3 4 5}

Who Is on the Research Team?

David Wyatt, MD

Principal Investigator

Syneos Health

Are You a Good Fit for This Trial?

This trial is for healthy individuals who meet specific health standards. The exact inclusion and exclusion criteria are not provided, but typically participants should have no significant medical conditions, not be on conflicting medications, and must be willing to follow the study procedures.

Inclusion Criteria

I am using or willing to use approved birth control methods if capable of becoming pregnant.

I understand the study and agree to follow its rules.

I am generally healthy based on recent medical exams and tests.

Exclusion Criteria

Participants known or suspected of not being able to comply with this study (eg, due to alcoholism, drug dependency or psychological disorder)

I don't have any major health issues apart from my current condition.

I received a vaccination within the last month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single ascending dose of MDI-2517 or placebo

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 days

Daily monitoring (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• MDI-2517

Trial Overview The trial is testing MDI-2517's safety and how it's processed in the body (pharmacokinetics) and its effects on the body (pharmacodynamics). It's a Phase 1 study where volunteers receive one dose of MDI-2517 to evaluate these factors.

How Is the Trial Designed?

Group I: Single Ascending Dose (SAD) 1 Active Control 2 Interventions

MDI-2517 tablet, single oral dose or placebo

Group II: SAD 2 Active Control 2 Interventions

less than or equal to twice the highest MDI2517 dose administered to date, or placebo

Group III: SAD 6 Active Control 2 Interventions

less than or equal to twice the highest MDI2517 dose administered to date, or placebo

Group IV: SAD 3 Active Control 2 Interventions

less than or equal to twice the highest MDI2517 dose administered to date, or placebo

Group V: SAD 4 Active Control 2 Interventions

less than or equal to twice the highest MDI2517 dose administered to date, or placebo

Group VI: SAD 5 Active Control 2 Interventions

less than or equal to twice the highest MDI2517 dose administered to date, or placebo

Group VII: SAD 7 Active Control 2 Interventions

less than or equal to twice the highest MDI2517 dose administered to date, or placebo

Group VIII: SAD 8 Active Control 2 Interventions

less than or equal to twice the highest MDI2517 dose administered to date, or placebo

Who Is Running the Clinical Trial?

MDI Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

50+

Published Research Related to This Trial

In a study involving 19 children with relapsed or refractory solid tumors, the maximum tolerated dose (MTD) of ABT-751 was determined to be 100 mg/m² per day, which is similar to the adult recommended dose of 200 mg fixed dose.

The treatment was associated with significant dose-limiting toxicities (DLTs) such as fatigue, sensory neuropathy, and hematologic issues, indicating that while ABT-751 can be administered, its tolerability in pediatric patients is limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 21 days every 28 days in pediatric patients with solid tumors. Fox, E., Maris, JM., Widemann, BC., et al.[2015]

The maximum tolerated dose (MTD) of S9788, a new drug aimed at overcoming multidrug resistance, was determined to be 96 mg/m2, with dose-limiting side effects primarily involving bradycardia and symptoms like faintness or dizziness.

S9788 did not enhance the toxicity of doxorubicin, and pharmacokinetic studies showed that the administration of S9788 did not affect the pharmacokinetics of doxorubicin, indicating a safe combination treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical and pharmacokinetic study of S9788, a new multidrug-resistance reversal agent given alone and in combination with doxorubicin to patients with advanced solid tumors. Tranchand, B., Catimel, G., Lucas, C., et al.[2013]

The Drug Adverse Reaction Database (DART) provides detailed information on 147 confirmed and 89 potential protein targets associated with adverse drug reactions (ADRs), which is crucial for understanding the mechanisms behind these reactions and aiding in drug discovery.

DART includes extensive data on 257 drugs and 1080 ligands, offering insights into their binding properties, physiological functions, and the specific adverse effects they may cause, making it a valuable resource for researchers and developers in pharmacology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Adverse Reaction Target Database (DART) : proteins related to adverse drug reactions. Ji, ZL., Han, LY., Yap, CW., et al.[2018]

In a study of 128 patients with highly active relapsing multiple sclerosis, cladribine tablets significantly reduced fatigue levels after 12 months, as indicated by a decrease in PROMIS® Fatigue MS scores.

Patients reported improved treatment satisfaction and work productivity, with TSQM scores rising from 52.2 to 81.4, suggesting that cladribine tablets not only help manage symptoms but also enhance overall quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Patient-Reported Outcomes in Patients with Relapsing Multiple Sclerosis Treated with Cladribine Tablets in the CLAWIR Study: 12-Month Interim Analysis. Rau, D., Müller, B., Übler, S.[2023]

The combination of capecitabine and vinorelbine was found to have a maximum-tolerated dose (MTD) with manageable toxicity, primarily neutropenia, in a study involving 33 patients with metastatic breast cancer.

This treatment demonstrated significant efficacy, achieving an overall response rate of 55% and a median overall survival of 19.2 months, even in patients who had previously failed anthracycline and/or taxane therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of capecitabine and vinorelbine in pretreated patients with metastatic breast cancer. Welt, A., von Minckwitz, G., Oberhoff, C., et al.[2020]

MGI 114, a novel antitumor compound derived from a mushroom toxin, showed significant antitumor activity in vitro against a variety of human tumors, including those from colon, kidney, breast, lung, ovary, melanoma, and neuroblastoma, with response rates between 50-80%.

The compound demonstrated effectiveness against tumors resistant to standard chemotherapy drugs, with a strong concentration-response relationship, indicating that higher doses led to greater antiproliferative effects, supporting its potential for further clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of MGI 114 (6-hydroxymethylacylfulvene, HMAF), a semisynthetic derivative of illudin S, against adult and pediatric human tumor colony-forming units. Hidalgo, M., Izbicka, E., Eckhardt, SG., et al.[2019]

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

In a clinical development program involving 1684 subjects and 2038 injections, OptiMARK demonstrated a safety profile comparable to Magnevist, with 31% of its injections associated with adverse events.

OptiMARK was found to be safe and well-tolerated, showing fewer adverse events compared to Magnevist (35%) and placebo (48%), indicating its potential as a reliable imaging agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The OptiMARK clinical development program: summary of safety data. Brown, JJ., Kristy, RM., Stevens, GR., et al.[2019]

A systematic review of 12 studies found that treatment with atidarsagene autotemcel (arsa-cel) offers significant benefits for patients with late-infantile (LI) and juvenile (EJ) metachromatic leukodystrophy (MLD), including improved cognitive and motor function, and increased survival compared to standard care and allogeneic hematopoietic stem cell transplantation (HSCT).

In contrast, HSCT showed no survival benefits for LI patients and was associated with severe complications, while some juvenile patients experienced stabilization of function but also disease progression, highlighting the superior safety and efficacy profile of arsa-cel over HSCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of clinical effectiveness and safety for historical and current treatment options for metachromatic leukodystrophy in children, including atidarsagene autotemcel. Armstrong, N., Olaye, A., Noake, C., et al.[2023]

The DIMDI provides comprehensive databases that contain valuable information on adverse drug reactions, which can help healthcare professionals and researchers understand the safety profiles of various medications.

Access to these databases is crucial for monitoring drug safety and improving patient care by identifying potential risks associated with drug treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Information on adverse drug reactions in databases hosted at the German Institute of Medical Documentation and Information (DIMDI)]. Bystrich, E.[2016]

Adverse drug reactions are a significant issue in both patient care and drug development, highlighting the need for improved prediction and prevention strategies in the pharmaceutical industry.

The integration of clinical knowledge and patient context into the drug design process is expected to enhance drug safety and efficacy, with advancements in data analysis and cloud computing likely to play a crucial role in this evolution over the next five years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fusion of nonclinical and clinical data to predict human drug safety. Johnson, DE.[2013]

Paclitaxel administered at maximal tolerated doses (MTD) showed minimal activity in treating newly diagnosed glioblastoma, with no radiographic responses observed in patients at or above the MTD, indicating limited efficacy for this cancer type.

The study found that the use of concomitant enzyme-inducing antiepileptic drugs (EIAEDs) significantly altered paclitaxel pharmacology, resulting in lower plasma concentrations and higher dose requirements, but did not negatively impact overall survival compared to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preirradiation paclitaxel in glioblastoma multiforme: efficacy, pharmacology, and drug interactions. New Approaches to Brain Tumor Therapy Central Nervous System Consortium. Fetell, MR., Grossman, SA., Fisher, JD., et al.[2017]

The International Working Group for Treatment Optimization in MS has developed evidence-based recommendations to improve treatment outcomes for patients experiencing suboptimal responses or intolerable side effects from disease-modifying drugs (DMDs).

The report outlines specific treatment pathways and therapeutic options to help clinicians better manage patients who are not responding adequately to their current MS therapies, ensuring a more personalized approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A recommended treatment algorithm in relapsing multiple sclerosis: report of an international consensus meeting. Karussis, D., Biermann, LD., Bohlega, S., et al.[2015]

Cladribine tablets are shown to be as effective as other modern disease-modifying drugs for multiple sclerosis, with a favorable safety profile and the best benefit/risk ratio among treatments for highly active MS.

The review emphasizes the importance of considering the unique benefits and characteristics of each disease-modifying drug, including alemtuzumab, ocrelizumab, and natalizumab, when prescribing for multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of the clinical benefits of second-line drugs modifying the course of multiple sclerosis]. Zhuravleva, MV., Davydovskaya, MV., Luchinina, EV., et al.[2020]

In a study of 644 patients with relapsing-remitting multiple sclerosis (RRMS) treated with dimethyl fumarate (DMF), the annualized relapse rate decreased from 0.52 to 0.35, indicating DMF's effectiveness in reducing relapses.

The study found that 22.2% of patients discontinued DMF due to side effects, primarily gastrointestinal discomfort and lymphopenia, suggesting that while DMF is generally safe and effective, some patients may experience significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of dimethyl fumarate in multiple sclerosis: a multi-center observational study. Miclea, A., Leussink, VI., Hartung, HP., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06453824

SAD Evaluation of Safety, Tolerability, PK, and PD of MDI- ... This is a Phase 1 study to test the safety and drug effects of MDI-2517 when given once in healthy volunteers. Detailed Description. This is a first-in-human ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06453824/sad-evaluation-of-safety-tolerability-pk-and-pd-of-mdi-2517-in-healthy-participants

SAD Evaluation of Safety, Tolerability, PK, and PD of MDI- ... This is a Phase 1 study to test the safety and drug effects of MDI-2517 when given once in healthy volunteers.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07220889

Study Details | NCT07220889 | Single Ascending Dose ... The goal of this clinical trial is to learn if drug MDI2517 is safe and to learn more about its drug effects in healthy participants.

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/mdi-therapeutics-phase-i-ssc-ild-study/

MDI Therapeutics doses first participants in Phase I SSc- ... The primary endpoint of the Phase I study is to assess the overall safety and tolerability of MDI-2517, an investigational inhibitor of ...

5. withpower.com withpower.com/trial/phase-1-safety-and-tolerability-4-2024-08d8e

MDI-2517 for Safety and Tolerability · Info for Participants The provided research does not contain specific safety data for MDI-2517. However, it references databases like DART and DIMDI that contain information on ...