ION440 for MECP2 Syndrome

Recruiting at 8 trial locations

Overseen By Ionis Pharmaceuticals

Age: Any Age

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Ionis Pharmaceuticals, Inc.

Must not be taking: Investigational drugs

Disqualifiers: Complex MECP2, Seizures, Infection, others

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

Compensation: Varies

Number of Visits: Unknown

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ION440 to assess its safety and tolerance in people with MECP2 Syndrome, a genetic condition that can cause developmental delays and other health issues. Participants will receive varying doses of ION440 to determine its effects on the body. The trial includes individuals diagnosed with MECP2 Syndrome who have been stable on their current medications for at least a month. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify that you must stop taking your current medications. However, you need to be on stable doses of your current medications for at least 3 months before starting the trial, unless the investigator decides otherwise.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ION440 is under study to determine its safety and effectiveness for treating MECP2 Duplication Syndrome. Initial studies focus on how well participants tolerate this treatment. As the study is in its early stages, researchers are still assessing its safety for humans. Early-phase trials mark the first time a treatment is tested in people, so information on side effects may be limited. Participants in these studies help researchers understand the treatment's safety and potential risks. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for MECP2 Syndrome?

Unlike the standard of care for MECP2 Syndrome, which often involves symptomatic treatments like physical therapy, occupational therapy, and medications for seizures or breathing issues, ION440 acts directly on the genetic level. Researchers are excited about ION440 because it is administered intrathecally, delivering the treatment directly into the spinal fluid, which could potentially offer more targeted and effective symptom management. By targeting the root genetic cause rather than just the symptoms, ION440 has the potential to provide a more comprehensive approach to managing this challenging condition.

What evidence suggests that ION440 could be an effective treatment for MECP2 Syndrome?

Research has shown that ION440 is under investigation as a potential treatment for MECP2 Duplication Syndrome. This condition occurs when an extra copy of the MECP2 gene leads to various developmental and neurological issues. ION440 aims to reduce the impact of this extra gene. Early results suggest it might help by normalizing the gene's activity. Although ION440 is not yet approved, initial research offers hope for those with this syndrome. In this trial, participants will receive different doses of ION440 or a sham procedure followed by ION440 to assess its effectiveness and safety. Additional studies are underway to evaluate its efficacy and safety further. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for children and adults with MECP2 Duplication Syndrome (MDS). Children must be aged 2-7, have a caregiver to consent and attend visits, while adults are eligible from ages 8-65. Participants need genetic confirmation of MDS and stable medication doses for at least 3 months.

Inclusion Criteria

I am a male between 2 and 65 years old.

I am between 8 and 65 years old.

I am between 2 and 7 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple Ascending Dose (MAD)

Participants are randomized to receive ION440 or sham in a double-blind manner

36 weeks

Regular visits for dosing and monitoring

Open-label Long-term Extension (LTE)

Participants receive ION440 for long-term evaluation

Up to 156 weeks

Regular visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ION440

Trial Overview The ATTUNE study tests the safety of ION440 when administered into the spinal fluid compared to a sham procedure. It aims to understand how the body handles ION440 and its effects on participants with MDS.

How Is the Trial Designed?

Group I: Cohort 3: ION440 Dose C Experimental Treatment 1 Intervention

Participants will receive ION440 intrathecally at Dose C during Part 1/MAD, followed by ION440 Dose C during Part 2/LTE.

Group II: Cohort 2: ION440 Dose B Experimental Treatment 1 Intervention

Participants will receive ION440 intrathecally at Dose B during Part 1/MAD, followed by ION440 Dose B during Part 2/LTE.

Group III: Cohort 1: ION440 Dose A Experimental Treatment 1 Intervention

Participants will receive ION440 intrathecally at Dose A during Part 1/MAD, followed by ION440 Dose A during Part 2/LTE.

Group IV: Sham Procedure Placebo Group 1 Intervention

During the Part 1/MAD period, a lumbar procedure (LP) will be performed at the same frequency as ION440 administration. Participants will not receive ITB injections during this period. It will be followed by the open-label Part 2/LTE period, where participants will receive ION440 at the same dose as their enrolled cohort (e.g. Dose A, Dose B or Dose C).

Who Is Running the Clinical Trial?

Ionis Pharmaceuticals, Inc.

Lead Sponsor

Trials

151

Recruited

27,800+

Dr. Brett P. Monia

Ionis Pharmaceuticals, Inc.

Chief Executive Officer since 2020

PhD in Pharmacology from the University of Pennsylvania, BSc in Molecular Biology and Analytical Chemistry from Stockton State College

Dr. Eric Bastings

Ionis Pharmaceuticals, Inc.

Chief Medical Officer

MD

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06430385

NCT06430385 | ATTUNE: A Study to Evaluate the Safety, ... This is a phase 1-2 randomized, double-blind, sham-controlled, multiple-ascending dose (MAD) study to evaluate ION440 in pediatric and adult participants ...

2. neurology.ionis.com neurology.ionis.com/sites/default/files/2024-10/MECP2%20Duplication%20Syndrome%20Clinical%20Trial%20Handout.pdf

MECP2 Duplication Syndrome Clinical Trial Handout.pdf - IONIS ION440 has not been evaluated for safety and efficacy by the US Food and. Drug Administration and is not indicated for the treatment of any disease. The ...

3. clinicaltrials.eu clinicaltrials.eu/inn/ion440/

Ion440 – Application in Therapy and Current Clinical ... ION440 is an investigational drug currently being studied for the treatment of MECP2 Duplication Syndrome (MDS).

4. dupmecp2.eu dupmecp2.eu/en/survey-results-2025/

Survey results: The global MECP2 Duplication community ... The results of this survey provide valuable insights into the perspectives and priorities of families affected by MECP2 Duplication Syndrome.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06430385?cond=MECP2%20Duplication%20Syndrome&viewType=Table&rank=3

ATTUNE: A Study to Evaluate the Safety, Tolerability ... The primary purpose of this study is to evaluate the safety and tolerability of ION440. Detailed Description. This is a phase 1-2 randomized, double-blind, sham ...

6. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-ion440-for-patients-with-mecp2-duplication-syndrome/

Study on the Safety and Effects of ION440 for Patients ... The purpose of the study is to evaluate the safety and tolerability of this treatment in patients with MECP2 Duplication Syndrome.

7. orpha.net orpha.net/en/research-trials/clinical-trial/714033?name=&mode=&country=&recruiting=0&terminated=0

Search for a clinical trial ... Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally-Administered ION440 in Patients With MECP2 Duplication Syndrome - AT.