Effects and Safety of Test drug ZYN002, applied as a gel onto the skin of children, adolescents and young adults with a certain hereditary disease called Fragile X Syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Harmony Biosciences Management Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

8 Jun 2023 → 30 Aug 2025

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Harmony Biosciences Management, Inc.

External identifiers

EU CT number

2024-513888-99-00

EudraCT number

2021-002542-33

ClinicalTrials.gov

NCT04977986

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of ZYN002 administered as a transdermal gel formulation in patients ages 3 to <23 years, in the treatment of behavioural symptoms of Fragile X Syndrome (FXS).

Secondary objectives 1

1. To further evaluate the efficacy of ZYN002 in the treatment of symptoms of FXS.

Conditions and MedDRA coding

Fragile X syndrome (FXS)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-003176-PIP02-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male or female children, adolescents, and young adults aged 3 to <23 years, at the time of Screening.
2. Patient resides with caregiver who will continue to provide consistent care throughout the study.
3. Judged by the Investigator to be in generally good health at Screening based upon the results of a medical history, physical examination, 12-lead ECG, and clinical laboratory test results. Laboratory results outside of the reference range must be documented as not clinically significant by both the Investigator and Sponsor.
4. Patients must have a diagnosis of FXS through molecular documentation of full mutation of the FMR1 gene documented through genetic testing at Screening.
5. Patients with a history of seizure disorders must currently be receiving treatment with a stable regimen of no more than two AEDs for the four weeks preceding study Screening; or must be seizure-free for one year if not currently receiving AEDs.
6. Patients who are taking psychotropic medication(s) should be on a stable regimen of no more than three such medications for at least four weeks preceding study Screening and must maintain that regimen throughout the study. Psychotropic medications include (but are not limited to) antipsychotics, antidepressants, anxiolytics, attention-deficit / hyperactivity disorder (ADHD) medications, and medications for sleep.
7. Patients have a body mass index between 12–30 kg/m2 (inclusive) and patients with a body mass index >30 kg/m2 and <40 kg/m2 with normal liver function laboratory values and with no immediate family history of fatty liver disease.

Exclusion criteria 10

1. Patient has transitioned to independent living or living in a residential facility such as a university setting or congregate care.
2. History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to ZYN002 or its excipients.
3. Exposure to any investigational drug or device ≤30 days prior to Screening or at any time during the study.
4. Patient has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels ≥2 times the upper limit of normal (ULN) or has alkaline phosphatase levels ≥3 times the ULN as determined from Screening safety laboratories.
5. Use of cannabis or any THC or CBD-containing product within 3 months of Screening Visit or during the study (aside from ZYN002).
6. Patient is using the following AEDs: clobazam, phenobarbital, ethosuximide, felbamate, or vigabatrin.
7. Patient is using any strong inhibitor/inducer of CYP3A4 or sensitive substrate for CYP3A4 including but not limited to the following medications: midazolam (except single doses administered for the purposes of obtaining blood samples and ECG's), oral ketoconazole, fluconazole, nefazadone, rifampin, alfentanil, alfuzosin, amiodarone, cyclosporine, dasatinib, docetaxol, eplerenone, ergotamine, everolimus, fentanyl, halofantrine, irinotecan, lapatinib, levomethadyl, lumefantrine, nilotinib, pimozide, quinidine, ranolazine, sirolimus, tacrolimus, temsirolimus, toremifene, tretinioin, vincristine, vinorelbine, and St. John's Wort.
8. Patients may not be taking any benzodiazepines (except single doses administered for the purposes of obtaining blood samples and ECG's) at screening or throughout the study.
9. Patient has an acute or progressive neurological disease, psychosis, schizophrenia, or any psychiatric disorder or severe mental abnormalities (other than FXS) that are likely to require changes in drug therapy or interfere with the objectives of the study or the ability to adhere to protocol requirements.
10. Any skin disease or condition, including eczema, psoriasis, melanoma, acne, contact dermatitis, scarring, imperfections, lesions, tattoos, or discoloration, that may affect treatment application, application site assessments, or absorption of the trial drug.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline to Week 18 in the ABC-CFXS Social Avoidance subscale score in patients with complete methylation of the FMR1 gene.

Secondary endpoints 13

1. Change from Baseline to Week 18 in ABC-CFXS Irritability subscale score in patients with complete methylation of the FMR1 gene.
2. Percent of patients with any improvement on the CaGI-C at Week 18 for Social Interactions among patients with complete methylation of the FMR1 gene.
3. Percent of patients rated as improved on the CGI-I scale (minimally, much, very much improved) at Week 18 among patients with complete methylation of the FMR1 gene.
4. Change from Baseline to Week 18 in the ABC-CFXS Social Avoidance subscale score among all randomized patients (complete and partial methylation of the FMR1 gene).
5. Percent of patients with a clinically meaningful within-subject improvement from Baseline in ABC-CFXS Social Avoidance subscale score at Week 18 among patients.
6. Percent of patients with a clinically meaningful within-subject improvement from Baseline in ABC-CFXS Irritability subscale score at Week 18 among patients.
7. Change from Baseline in ABC-CFXS Social Avoidance and Irritability subscale scores at Weeks 10 and 14 in patients.
8. Change from Baseline in ABC-CFXS Socially Unresponsive/Lethargic, Stereotypy, Inappropriate Speech, and Hyperactivity subscale scores at Weeks 10, 14, and 18 in patients.
9. Percent of patients with any improvement on the CaGI-C at Week 18 for Social Avoidance and Isolation, Irritable and Disruptive Behaviors, and Overall Behavior among patients.
10. Percent of patients with any improvement on the CaGI-C at Week 18 for Social Interactions among all randomized patients.
11. Percent of patients rated as improved on the CGI-I scale (minimally, much, very much improved) at Week 18 among all randomized patients.
12. Incidence of TEAEs and SAEs by relationship to treatment and severity; incidence of SAEs/AEs leading to treatment discontinuation.
13. Changes in vital signs, clinical laboratory tests, and ECG.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Harmony Biosciences Management Inc.

Sponsor organisation

Harmony Biosciences Management Inc.

Address

630 West Germantown Pike Suite 215

City

Plymouth Meeting

Postcode

19462-1069

Country

United States

Scientific contact point

Organisation

Harmony Biosciences Management Inc.

Contact name

Senior Medical Director, Clinical Development

Public contact point

Organisation

Harmony Biosciences Management Inc.

Contact name

Vice President, Regulatory Affairs

Third parties 13

Sponsor responsibilities

Article 77 compliance

Harmony Biosciences Management Inc.

Contact point sponsor

Harmony Biosciences Management Inc.

Article 77 implementation

Harmony Biosciences Management Inc.

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications