Marigold Study

The Marigold Study**

The first double-blind placebo controlled study providing evidence of efficacy specific to CDD.

**This trial is no longer enrolling patients.

It was hypothesized that boosting the signaling capacity of receptors in the brain may improve seizure control and other behavioral abnormalities in children with the CDKL5 mutation.

Currently, there are no approved therapies for CDD. Any therapy that reduces the frequency, duration or severity of seizures may positively impact quality of life for the child and family. The Marigold study explored whether ganaxolone, an investigational medication could reduce seizures, increase seizure free days and improve behavior in children with CDD.

About CDD

CDKL5 Deficiency Disorder (CDD) is a serious and rare genetic disorder that is caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, located on the X chromosome. The CDKL5 gene produces a protein that is important for normal brain development and function.

CDD predominantly affects girls and is characterized by early onset intractable seizures, severe developmental delay, disturbed sleep and severe intellectual/ gross motor impairment. Typically, the seizures are resistant to conventional antiepileptic medication. Treatment-resistant epilepsy can be fatal and patients are often treated with high doses of multiple antiepileptic drugs (AEDs) that worsen the cognitive, behavioral and physical consequences of the underlying disorder. Together, these children and young adults experience major impairments to quality of life. Currently, there are no approved therapies for CDD. Any therapy that reduces the frequency, duration or severity of seizures may positively impact quality of life for the child and family.

What was the Marigold Study?

First double-blind placebo controlled study providing evidence of efficacy specific to CDD.

First Phase 3 trial to examine three times a day dosing of ganaxolone in pediatric patients.

In the trial, patients given ganaxolone showed a significant 30.7 percent median reduction in 28-day major motor seizure frequency, compared to a 6.9 percent reduction for those receiving the placebo, achieving the primary endpoint (p=0.0036). The trial’s primary efficacy endpoint was the percentage change in 28-day frequency of major motor seizures during the double-blind phase relative to the 6-week prospective baseline period. Ganaxolone was generally well tolerated with a safety profile consistent with previous clinical studies. The most frequent adverse event was somnolence.

“We believe we are one step closer to providing the first treatment indicated for CDD…” said Scott Braunstein, M.D.

Children that Qualified

CDKL5 mutation confirmed by a genetic laboratory
Between the ages of 2-21 years
Suffer from approximately 16 or more major motor or drop seizures per month

The study doctor required a pre-screening for the patient and asked questions about the patient’s medical history and seizures to see if the patient could participate in the study. The child’s families were asked to keep track of seizures (including the type and number of seizures the child had every day, and the days when the child didn’t have any seizures) for 8 weeks. There was no cost to the patients and their families for participating in the study. If financial assistance was necessary to get a required study visit, the sponsor reimbursed for reasonable expenses (parking and travel).

does my child qualify

Participation in the Marigold Study was completely voluntary.

Clinical Research

Clinical research studies evaluate investigational medications to determine if they are safe and effective for patients before they are made available to the public. Studies are carefully designed and monitored by health professionals, with patient safety as a priority. Before enrolling in clinical research studies, participants review and sign an informed consent document, stating that the study details have been explained to them and their questions have been answered. This document is not a contract; participation in a clinical research study is completely voluntary and study participants can leave the study for any reason at any time.

Frequently Asked Questions

Who participated in this study?

Individuals between the ages of 2 and 21 with early-onset, difficult-to-control seizures, neurodevelopmental impairment, and a confirmed pathogenic CDKL5 gene variant were eligible for the study. See clinicaltrials.gov for details.

What treatment options were provided?

Patients were randomized into the clinical trial and received either ganaxolone or a placebo (non-active substance), in addition to their standard anti-seizure treatment. The drug was administered as either a drinkable liquid or as a capsule, and it was taken with food. Patients had to maintain stable background medications while in the clinical trial.

Were there side effects?

Ganaxolone has been shown to be generally safe and well-tolerated in clinical studies to date. Over 1,600 people of all ages have taken ganaxolone, some for as long as four years. Common side effects included sleepiness, dizziness, and fatigue.

What was the impact on patients?

Previous studies had shown that ganaxolone reduced seizures in CDD. This trial intended to find out if ganaxolone was more effective in reducing seizures compared to placebo and whether there are other benefits associated with ganaxolone treatment. Because of the nature of the trial, even if ganaxolone was effective, some patients might have been in the control group that received the placebo.