A trial to learn how a trial drug called carbetocin works in reducing uncontrollable hunger in people with Prader-Willi syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Acadia Pharmaceuticals 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

10 Jan 2025 → 20 Aug 2025

Decision date (initial)

2024-05-29

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Acadia Pharmaceuticals Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy, Pharmacokinetic

To investigate the efficacy of treatment with carbetocin nasal spray versus placebo on
hyperphagia in Prader-Willi Syndrome (PWS).

Secondary objectives 1

1. To investigate the efficacy of treatment with carbetocin versus placebo on Prader-Willi Syndrome (PWS) and Hyperphagia in PWS

Conditions and MedDRA coding

Hyperphagia related behaviour associated with Prader-Willi Syndrome (PWS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Informed consent prior to the conduct of any study procedures is required as follows: a. For subjects who are minors: written informed consent will be obtained from the legally acceptable representative (LAR) (or LARs where local regulations require) or from the minor him/herself if deemed able by the Investigator per local regulations. When consent is obtained from the LAR, the subject should provide written or oral assent if deemed able by the Investigator, and according to local regulations. b. For subjects who are of legal age of consent: written informed consent will be obtained from the subject if the subject is not under guardianship and is deemed able by the Investigator. If the subject is under guardianship or deemed not able to provide consent, the subject should provide written or verbal assent if deemed able by the Investigator, and a written informed consent will be obtained from the subject’s LAR(s) according to local regulations. c. The subject’s caregiver provides written consent to participate as an informant in study assessments. The caregiver may or may not be a LAR.
2. Is a male or female 5 to 30 years of age, inclusive, at Screening.
3. Has PWS with a documented disease-causing mutation.
4. Has increased appetite with decreased satiety accompanied by food seeking (consistent with PWS Nutritional Phase 3).
5. Has an HQ-CT score of ≥13 at Screening and Baseline.
6. Has a CGI-S for hyperphagia in PWS score of ≥4 at Screening and Baseline.
7. Lives with a caregiver who understands and is willing and able to adhere to study-related procedures and is willing to participate in all study visits. a. The subject must be under the caregiver’s consistent care and observation during the study when not attending school or day programs. b. The caregiver should be a family member of the subject or someone whose association with the subject is the equivalent of a family relation. OR The caregiver is not a family member but has cared for the subject for at least 6 months, plans to continue to care for the subject during this study, and spends time with the subject 5 days per week. c. The caregiver must have sufficient language skills to complete the assessments in the language of the assessments and be able to utilize electronic media for study visits and questionnaires. Caregivers will be trained to use the electronic media by which assessments are completed and respond in the local language.
8. Caregiver is able to receive study drug shipments, where permitted, and store study drug per instructions during the study.
9. Caregiver is able to snap the intranasal (IN) pump device onto the study drug vial.
10. Caregiver agrees to request and provide medical records to the investigative site.
11. Has been on a stable dose of any allowed chronic concomitant medications for at least 3 months prior to the Screening visit. Adjustments in growth hormone dose or medication changes that are not clinically significant in the judgment of the Investigator (i.e., having no reasonable possibility of causing changes in mood, behavior, or appetite, or otherwise affecting study endpoints) are allowed. If the medication was discontinued, the discontinuation occurred at least 2 weeks or 5 half-lives (whichever is greater) prior to Screening.
12. This criterion for female subjects varies depending on the location of the subject's clinical site due to local regulatory requirements (or requests). a) In the EU: If the subject is female, she must not be pregnant or breastfeeding. Subjects of childbearing potential should abstain from sexual activity for the duration of the study and for at least 30 days thereafter. If a subject is sexually active or becomes sexually active during the study, she must use a highly effective contraceptive method per Clinical Trials Facilitation and Coordination Group (CTFG) recommendations. The contraceptive method should be used for at least 1 month prior to Baseline, throughout the study, and for at least 30 days thereafter. b) In the UK: : If the subject is female, she must not be pregnant or breastfeeding. Subjects of childbearing potential (including subjects who reach menarche during the study) should abstain from sexual activity for the duration of the study and for at least 30 days thereafter. If a subject is sexually active or becomes sexually active during the study, she must use an intrauterine device (IUD) plus barrier method (diaphragm, cap, or sponge with spermicide), OR she must use one of these acceptable methods of contraception and her partner must use a condom for at least 1 month prior to Baseline, throughout the study, and for at least 30 days thereafter. A female is considered of childbearing potential following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. c) In North America: If the subject is female, she must not be pregnant or breastfeeding. Subjects of childbearing potential should abstain from sexual activity for the duration of the study and for at least 30 days thereafter. If a subject is sexually active or becomes sexually active during the study, she must use a non-user-dependent method of contraception (e.g., IUD or implant) or a user-dependent hormonal method of contraception (e.g., injection, oral, transdermal, or intravaginal). The contraceptive method should be used for at least 1 month prior to Baseline, throughout the study, and for at least 30 days thereafter.
13. This criterion for male subjects varies depending on the location of the subject’s clinical site due to local regulatory requirements (or requests). a) In the EU: If the subject is male and sexually active, he must use a condom (even if vasectomized) from the time of Screening until 90 days after the last dose of study drug. The male subject’s female partner must use a highly effective contraceptive method per CTFG recommendations. The female partner’s contraceptive method should be used for at least 1 month prior to Baseline, throughout the study, and for at least 30 days thereafter; OR the male subject must not have a female partner of childbearing potential. Subject must also agree not to donate sperm from the time of Screening until 90 days after the last dose of study drug. b) In the UK: If the subject is male and sexually active, he must use a condom (even if vasectomized) from the time of Screening until 90 days after the last dose of study drug. The male subject’s female partner must use either an IUD or a barrier method (e.g., diaphragm, cap, or sponge with spermicide; a female condom in combination with a male condom is not acceptable); OR the male subject must not have a female partner of childbearing potential. Subjects must also agree not to donate sperm from the time of Screening until 90 days after the last dose of study drug. c) In North America: If the subject is male and sexually active, he must use a condom (even if vasectomized) from the time of Screening until 90 days after the last dose of study drug. The male subject’s female partner must use either a non-user-dependent method of contraception (e.g., IUD or implant) or a user-dependent hormonal method of contraception (e.g., injection, oral, transdermal, or intravaginal). The female partner’s contraceptive method should be used for at least 1 month prior to Baseline, throughout the study, and for at least 30 days thereafter; OR the male subject must not have a female partner of childbearing potential. Subject must also agree not to donate sperm from the time of Screening until 90 days after the last dose of study drug.

Exclusion criteria 30

1. 1. Is genetically diagnosed with Schaaf-Yang syndrome or another genetic, hormonal, or chromosomal cognitive impairment besides PWS.
2. 10. Has another nasal disorder that may affect deposition of IN medication.
3. 11. Has known hypersensitivity to any component of study drug.
4. 12. Has been diagnosed with cancer (except managed basal cell carcinoma or squamous cell carcinoma of the skin).
5. 13. Has had clinically significant irritability or agitation, requiring initiation of antipsychotic medication, within the 6 months prior to the Screening visit.
6. 14. Has used prostaglandins, prostaglandin analogues, or prostaglandin agonists in the 3 months prior to the Baseline visit. Inhibitors of prostaglandin synthesis, such as nonsteroidal anti-inflammatory drugs, are not exclusionary.
7. 15. Has started a glucagon-like peptide 1 (GLP-1) agonist within the 6 months prior to the Screening visit. Treatment with GLP-1 agonist is allowed if the subject has been taking it for more than 6 months prior to Screening.
8. 16. Has used oxytocin, desmopressin (DDAVP), tesofensine, diazoxide choline, melanocortin-4 receptor (MC4R) agonists (e.g., setmelanotide), or any medication approved to treat hyperphagia within 6 months prior to the Baseline visit.
9. 17. Has active psychotic symptoms, a history of psychotic symptoms, or a psychotic disorder.
10. 18. Has a history of suicide attempt or inpatient psychiatric hospitalization.
11. 19. Has new food-related interventions, including environment or dietary restrictions, within 1 month prior to the Screening visit or during the Screening period (i.e., before the Baseline visit).
12. 2. Has an active upper respiratory infection at the Screening visit or the Baseline visit.
13. 20. Has participated in an interventional research study involving another investigational medication or device in the 6 months prior to the Screening visit.
14. 21. Has a history of or current abuse of/dependence on alcohol or illicit drugs.
15. 22. Has a clinically significant abnormal laboratory value at Screening. Laboratory testing may be repeated during the Screening period with agreement of the Medical Monitor.
16. 23. Has serum potassium below the normal range (according to the central laboratory) at Screening. Serum potassium may be repeated during the Screening period with the agreement of the Medical Monitor.
17. 24. Has a clinically significant thyroid function test result at Screening (as measured by thyroid stimulating hormone [TSH] and reflex free thyroxine [T4]). If TSH is abnormal and the reflex free T4 is normal, the subject may be randomized.
18. 25. Has clinically significant abnormality in vital signs at Screening or Baseline.
19. 26. Has any of the following: a. QTcF interval of >450 ms at Screening or Baseline (before dosing) b. History of a risk factor for torsades de pointes (e.g., heart failure or family history of long QT syndrome) c. History of clinically significant QT prolongation that is deemed to put the subject at increased risk of clinically significant QT prolongation d. Has any other clinically significant finding on ECG at Screening or Baseline (before dosing)
20. 27. Has a positive pregnancy test at Screening.
21. 28. Is an employee or is a family member of an employee of Acadia Pharmaceuticals Inc.
22. 29. Is judged by the Investigator or the Medical Monitor to be inappropriate for the study for any reason.
23. 3. Has any clinically significant cardiovascular disorder, renal, hepatic, gastrointestinal, or respiratory disease, including severe asthma.
24. 4. Has a history of, or current, cerebrovascular disease, brain trauma, epilepsy, or frequent migraines. A history of febrile seizures is not exclusionary.
25. 5. Has significant, uncorrected visual or uncorrected hearing impairment.
26. 6. Has had major surgery within 1 month of the Screening visit or planning to have surgery during the study.
27. 7. Has had nasal surgery within 1 month of Screening visit or planning to have nasal surgery during the study.
28. 8. Is unwilling to abstain from nasal saline, other nasal irrigation, and other IN medications medications (including IN vaccines) within two hours before or after administration of study drug during the Screening period and through the treatment period of the study.
29. 9. Has had more than three episodes of sinusitis in the 12 months prior to the Baseline visit.
30. 30. In France only: Is under court protection, not affiliated to a social security system, or a protected adult under French law (Art. L. 1121-6, Art. L. 1121-8, Art. L. 1121-8-1).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score - change from Baseline at Week 12

Secondary endpoints 4

1. Clinical Global Impression–Severity (CGI-S) for PWS score – change from Baseline at Week 12
2. Clinical Global Impression–Change (CGI-C) for PWS score at Week 12
3. Percentage of subjects with treatment response (defined as improvement from Baseline ≥8 points) based on the HQ-CT at Week 12
4. CGI-S for hyperphagia in PWS score – change from Baseline at Week 12

Investigational products

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

Test 1

Placebo 1

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

Alana Salvucci

Public contact point

Organisation

Acadia Pharmaceuticals Inc.

Contact name

Andrew McGinn

Third parties 10

Locations

5 EU/EEA countries · 11 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 175 files

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

Application history

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