A study to see how well KarXT works and how well tolerated it is in participants with psychosis associated with Alzheimer’s disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karuna Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03], Diseases [C] - Nervous System Diseases [C10]

Trial duration

11 Apr 2024 → ongoing

Decision date (initial)

2024-02-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Karuna Therapeutics Inc.

External identifiers

EU CT number

2023-504416-16-00

ClinicalTrials.gov

NCT06126224

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Others, Safety, Efficacy, Pharmacokinetic

To evaluate the efficacy of KarXT compared with placebo in the treatment of psychosis in subjects with psychosis associated with AD as measured by the Neuropsychiatric Inventory-Clinician (NPI-C): Hallucinations and Delusions (H+D) score

Secondary objectives 2

1. •To evaluate the efficacy of KarXT compared with placebo in global severity of illness with the Clinical Global Impression – Severity (CGI-S) scale: CGI-S requires the assessor to consider aspects of the psychosis (hallucinations and delusions) prior to providing a global assessment of severity
2. •To evaluate the efficacy of KarXT compared with placebo using the following: - NPI-C Core score: hallucinations, delusions, agitation, and aggression domains, - NPI-C: Agitation score - NPI C Core Score: Caregiver Distress scale (Hallucinations, Delusions, Agitation, and Aggression domains) - Responder rate defining a responder as NPI-C: H+D (Hallucinations and Delusions) score ≥ 40% improvement

Conditions and MedDRA coding

Psychosis Associated with Alzheimer’s Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. 1.Is a male or female aged 55 to 90 years, inclusive, at Screening (Visit 1)
2. 2.Can understand the nature of the trial and protocol requirements and provide informed consent (IC) before any study assessments are performed. If the subject is deemed not competent to provide IC, the following requirements for consent must be met: a.The subject’s legally acceptable representative must provide IC b.The subject must provide informed assent
3. 3.Meets clinical criteria for 1 of the following disorders: - Possible AD or Probable AD (refer to Appendix 1 National Institute on Aging – Alzheimer’s Association Guidelines for All cause Dementia and Alzheimer’s Disease)
4. 4.Has a magnetic resonance imaging (MRI) or computed tomography (CT) scan of the brain (completed within the past 5 years) taken during or subsequent to the onset of dementia to rule out other central nervous system (CNS) disease that could account for the dementia syndrome, e.g., major stroke, neoplasm, subdural hematoma. If not available, a non-contrast brain MRI or non-contrast head CT must be done during Screening
5. 5.Living at the same home or residential assisted-living facility for a minimum of 6 weeks before Screening (Visit 1)
6. 6.Capable of self-locomotion (alone or with the aid of an assistive device) and have an identified study partner who should have daily contact (approximately 10 hours a week or more) and is willing to: a.Attend all visits and report on subject’s status b.Oversee subject compliance with medication and study procedures c.Participate in the study assessments and provide IC to participate in the study
7. 7.History of psychotic symptoms (meeting International Psychogeriatric Association criteria) (Cummings 2020) for at least 2 months prior to Screening (Visit 1) (subjects may or may not have symptoms of agitation)
8. 8.CGI-S scale with a score ≥ 4 (moderate) at Screening (Visit 1) and at Visit 2. CGI-S requires the assessor to consider aspects of the psychosis (hallucinations and delusions) prior to providing a global assessment of severity
9. 9.AD subjects are required to have NPI-C: H+D score of ≥ 6 AND meet at least 1 of the following criteria at Screening (Visit 1) and Visit 2: a.Moderate to severe delusions, defined as NPI-C: Delusions domain score of ≥ 2 on 2 of the 8 items OR b.Moderate to severe hallucinations, defined as NPI-C: Hallucinations domain score of ≥ 2 on 2 of the 7 items
10. 10. MMSE score of 8 to 22, inclusive, at Screening (Visit 1)
11. 11.If the subject is taking a cholinesterase inhibitor and/or memantine, they must have been on a stable dose for 6 weeks prior to Screening (Visit 1) and willing to maintain a stable dose for the duration of the study
12. 12.Subject is willing and able to visit the clinic in an outpatient setting for the study duration, follow instructions, and comply with the protocol requirements
13. 13.BMI must be within 18 to 40 kg/m2 inclusive
14. 14.Female subjects must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP), or men whose sexual partners are WOCBP, must be able and willing to use at least 1 highly effective method of contraception during the study and for at least 1 menstrual cycle (e.g., 30 days) after the last dose of IMP. Sperm donation is not allowed for 30 days after the final dose of the IMP. A female subject is considered to be a WOCBP after menarche and until she is in a postmenopausal state for 12 months or otherwise permanently sterile (for which acceptable methods include hysterectomy, bilateral salpingectomy, or bilateral oophorectomy)

Exclusion criteria 25

1. 1.Psychotic symptoms that are primarily attributable to a condition other than the AD causing the dementia, e.g., schizophrenia, schizoaffective disorder, delusional disorder, or mood disorder with psychotic features
2. 2.History of major depressive episode with psychotic features during the 12 months prior to Screening (Visit 1)
3. 3.History of bipolar disorder, schizophrenia, or schizoaffective disorder
4. 4.Significant or severe medical conditions including pulmonary, hepatic*, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, cardiovascular, or oncologic disease or any other condition that, in the opinion of the Investigator, could jeopardize the safety of the subject, ability to complete or comply with the study procedures or validity of the study results *Note: participants with any grade of hepatic impairment (mild [Child-Pugh Class A], moderate [Child-Pugh Class B], and severe [Child-Pugh Class C]) will be excluded
5. 5.Significant and severe renal impairment based on a screening cutoff for estimated glomerular filtration rate of ≤ 50 mL/min/1.73 m2
6. 6.History of ischemic stroke within 12 months prior to Screening (Visit 1) or any evidence of hemorrhagic stroke
7. 7.History of cerebral amyloid angiopathy, epilepsy, CNS neoplasm, unstable thyroid function, or unexplained syncope
8. 8.Any of the following: a.New York Heart Association Class II or greater congestive heart failure b.Grade 2 or greater angina pectoris c. History of Sustained ventricular tachycardia d. History of Ventricular fibrillation e. History of Torsade de pointes f. History of Implantable cardiac defibrillator
9. 9.Myocardial infarction within the 6 months prior to Screening (Visit 1)
10. 10.Personal or family history of symptoms of long QT syndrome as evaluated by the Investigator
11. 11.Human immunodeficiency virus (HIV), cirrhosis, biliary duct abnormalities, active biliary disease (e.g., symptomatic gallstones), hepatobiliary carcinoma, and/or active hepatic viral infections as indicated by medical history or LFT results
12. 12.History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the Investigator
13. 13.Male subjects are excluded from the study if any of the following criteria apply: a.History of bladder stones b.History of recurrent urinary tract infections c.Serum prostate specific antigen > 10 ng/mL at Screening (Visit 1) d.An IPSS score of 5 (almost always) on items 1, 3, 5, or 6 e.A sum of scores on IPSS items 1, 3, 5, and 6 of ≥ 9
14. 14.History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months
15. 15.Risk of suicidal behavior during the study as determined by the Investigator’s clinical assessment and/or C-SSRS as confirmed by the following: a.Answers “Yes” on items 3, 4, or 5 (C-SSRS – ideation) with the most recent episode occurring within the 2 months before screening or, b.Answers “Yes” to any of the 5 items (C-SSRS behavior) with an episode occurring within the 12 months before Screening
16. 16.Clinically significant abnormal finding on the physical examination, ECG, or clinical laboratory results at Screening (Visit 1)
17. 17.Urine toxicology screen is positive for substances other than cannabis or benzodiazepines (both cannabis and short- or medium-acting benzodiazepines are allowed in limited quantities during the study) unless approval has been given by the Medical Monitor
18. 18.Recent history of receiving monoamine oxidase inhibitors, anticonvulsants (e.g., lamotrigine, divalproex), mood stabilizers (e.g., lithium), tricyclic antidepressants (e.g., imipramine, desipramine), or any other psychoactive medications except for as needed anxiolytics (e.g., lorazepam) a.Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors taken at a stable dose for at least 8 weeks prior to Screening (Visit 1) may be permitted b.Mirtazapine or trazodone may be used as a hypnotic if started at least 8 weeks prior to Screening (Visit 1) c. If needed, an extension (up to 2 weeks) of the Screening Period may be allowed with approval of the Sponsor/Medical Monitor
19. 19.If, in the opinion of the Investigator and/or Sponsor/Medical Monitor, subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the Investigator and/or Sponsor/Medical Monitor, may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements
20. 20. Known positive test for coronavirus disease 2019 (COVID-19) within 2 weeks before or at Screening (Visit 1); antigen or polymerase chain reaction local testing can be done at the discretion of the Investigator
21. 21.Unable to taper and discontinue a concomitant medication that would preclude participation in this study (e.g., cannot stop potent anticholinergic or antihistamine medication)
22. 22.Prior exposure to KarXT
23. 23.History of hypersensitivity to KarXT excipients or trospium chloride
24. 24.Experienced any significant AEs due to trospium, including a known hypersensitivity to trospium
25. 25.Participation in another clinical study in which the subject received an experimental or investigational drug within 3 months before Screening (Visit 1) or has participated in more than 2 clinical studies in the 12 months prior to Screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in NPI-C: H+D score

Secondary endpoints 3

1. •Change in the CGI-S scale: CGI-S requires the assessor to consider aspects of the psychosis (hallucinations and delusions) prior to providing a global assessment of severity
2. •Change in the: - NPI-C Core score: hallucinations, delusions, agitation, and aggression domains - NPI-C: Agitation score - NPI-C Core score: Caregiver Distress scale (Hallucinations, Delusions, Agitation, and Aggression domains)
3. •Responder rate defined as NPI-C: H+D score ≥ 40% improvement

Investigational products

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

Test 5

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karuna Therapeutics Inc.

Sponsor organisation

Karuna Therapeutics Inc.

Address

Route 206, Province Line Road Province Line Road

City

Princeton

Postcode

08543

Country

United States

Scientific contact point

Organisation

Karuna Therapeutics Inc.

Contact name

GSM-CT

Public contact point

Organisation

Karuna Therapeutics Inc.

Contact name

GSM-CT

Third parties 16

Locations

4 EU/EEA countries · 13 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

Documents 34 files

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

Application history

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