A study to evaluate the long-term safety and tolerability of pimavanserin after 52 weeks of treatment in children and adolescents with ASD

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Acadia Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

27 Feb 2023 → 9 Feb 2025

Decision date (initial)

2024-08-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512202-25-00

EudraCT number

2021-005388-32

ClinicalTrials.gov

NCT05555615

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

• To evaluate the long-term safety and tolerability of pimavanserin after 52 weeks of treatment in children and adolescents with ASD

Secondary objectives 1

1. To evaluate the continued response to long-term pimavanserin treatment in children and adolescents with ASD

Conditions and MedDRA coding

Irritability associated with autistic disorder in children and adolescents with ASD

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Study Population_Has completed the treatment period of the antecedent double-blind study.
2. Study Population_Informed consent prior to the conduct of any study procedures is required as follows: a. The subject should provide written or oral assent if deemed able by the Investigator. b. The subject's parent/LAR must provide written consent. The subject's parent/LAR must be considered reliable by the Investigator, able to complete assessments regarding the subject's development and behavior throughout the study, and able to help ensure compliance with study treatment, study visits, and protocol procedures. c. If a person other than the parent/LAR has been designated as a caregiver for the purpose of providing input for caregiver-reported scales, that person must also provide written consent. Such a designee should be a family member, adult and responsible, living with or in very frequent contact with the subject participating in the study, who is committed to providing responses for the caregiver-reported scales for the duration of the study. The process of obtaining informed consent will be conducted in accordance with institutional review board (IRB) or ethics committee (EC) policy and applicable local law.
3. Study Population_In the Investigator's opinion, the subject, to the best of his/her ability, the parent/LAR, and the designated caregiver (if applicable, and in accordance with IRB or EC policy and applicable local law) are able to understand the nature of the study, follow protocol requirements and be willing to comply with study drug administration requirements. Psychiatric Diagnosis
4. Psychiatric Diagnosis_Continues to be both clinically stable and not at imminent risk of suicide or injury to self, others, or property, in the opinion of the Investigator.
5. Psychiatric Diagnosis_Continues to be medically stable at enrollment, in the opinion of the Investigator.
6. Contraceptives_Female subjects who participate in this study must either be unable to become pregnant (e.g., premenarchal, surgically sterile, etc.) -OR- must agree to use two clinically acceptable methods of contraception (e.g., oral, intrauterine device [IUD], diaphragm plus spermicide, injectable, transdermal or implantable contraception) during the treatment period, and for at least 45 days after last dose. All female subjects of childbearing potential must have a negative urine human chorionic gonadotropin (hCG) pregnancy test at Contraceptives: Baseline and all clinic visits. Females of childbearing potential are defined as females who have begun menstruating.

Exclusion criteria 11

1. Study Population_Subject or parent/LAR is judged by the Investigator to be inappropriate for the study (e.g., significantly noncompliant in the antecedent double-blind study).
2. Medical Criteria_Weight <15 kg.
3. CNS, Psychiatric, and Illicit Drug Use Criteria_Requires treatment with a medication prohibited by the protocol, including concomitant psychotropic drugs targeting irritability, including those used off-label (clonidine, guanfacine, and propranolol; lithium, valproate), medications that prolong the QT interval; and strong cytochrome P450 (CYP) 3A4 enzyme (CYP3A4) inhibitors and inducers.
4. CNS, Psychiatric, and Illicit Drug Use Criteria_Is at a significant risk of suicide, or is a danger to self or others, in the opinion of the Investigator based upon all available sources of information including C-SSRS (positive answer to suicidal ideation questions 4 or 5 [or positive answer to suicidal behavior questions at Baseline]).
5. CNS, Psychiatric, and Illicit Drug Use Criteria_Is at risk of significant violent behavior to the extent that participation would pose an undue risk to other patients, caregivers, or others in the opinion of the Investigator
6. CNS, Psychiatric, and Illicit Drug Use Criteria_Has a positive urine drug test at Baseline. For study eligibility, the urine toxicology (drug) screen (UDS) must be negative for any substance for which the subject does not have a valid prescription.
7. Medical Criteria_Has developed a serious and/or unstable psychiatric, neurologic, cardiovascular (e.g., long QT syndrome, torsade de pointes, unstable cardiac syndrome or syncope, congestive heart failure, ongoing uncorrected hypokalemia or hypomagnesemia, non-sustained or sustained ventricular tachycardia), respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies that, in the judgment of the Investigator, would jeopardize the safe participation of the subject in the study, or has major surgery planned during the study.
8. Medical Criteria_Has experienced any change in medical or treatment status that may increase the risk associated with taking pimavanserin, would interfere with safety assessments, or would confound the interpretation of study results, based on the Investigator's judgment.
9. Medical Criteria_For age <13 years, a resting position (sitting or supine) systolic (SBP) and/or diastolic blood pressure (DBP) level ≥90th percentile for genderspecific age and height charts from the National Heart and Lung Institute (NHLI), at Baseline. For age ≥13 years a resting position (sitting or supine) SBP ≥120 mmHg and/or a DBP ≥80 mmHg, at Baseline.
10. Medical Criteria_Has a clinically significant abnormal ECG at Baseline or any of the following cardiac conduction abnormalities: a. Corrected QT interval using Fridericia's correction method (QTcF) ≥ 450 ms b. PR interval on ECG >220 ms c. Evidence of second- or third-degree atrioventricular block d. Evidence of complete left bundle branch block e. Intraventricular conduction delay with QRS interval on ECG (QRS) >110 ms f. QRS or T wave morphology that could, in the Investigator's opinion, render QT interval assessment unreliable g. Sick sinus syndrome h. Non-sinus rhythm i. Resting heart rate <50 beats per minute. One repeat set of triplicate ECGs is allowed at Baseline
11. Medical Criteria_In Italy only: Has a sensitivity to any compound present in pimavanserin or any metabolites or compounds listed in the Investigator’s brochure as being present in this medication

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Treatment-emergent adverse events (TEAEs) Safety will also be evaluated by analyses of the following: • Vital signs • Weight and body mass index (BMI) • 12-lead electrocardiograms (ECGs) • Physical examination results • Clinical laboratory tests (including urinalysis) and hormonal assessments • Columbia–Suicide Severity Rating Scale (C-SSRS) • Extrapyramidal Symptom Rating Scale Abbreviated (ESRS-A).

Secondary endpoints 1

1. • Proportion of subjects who have at least 25% reduction in the Aberrant Behavior Checklist– Irritability (ABC-I) subscale score AND a Clinical Global Impression–Improvement (CGI-I) of irritability score of 1 (very much improved) or 2 (much improved) compared to the antecedent study baseline status at Week 52.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Acadia Pharmaceuticals Inc.

Sponsor organisation

Acadia Pharmaceuticals Inc.

Address

12830 El Camino Real Suite 400

City

San Diego

Postcode

92130-2976

Country

United States

Scientific contact point

Organisation

Acadia Pharmaceuticals Inc.

Contact name

Reg Affairs

Public contact point

Organisation

Acadia Pharmaceuticals Inc.

Contact name

Reg Affairs

Third parties 9

Locations

5 EU/EEA countries · 35 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 44 files

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

Application history

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