A rollover study for subjects that complete KAR-012 trial, to assess Long-term Safety and Tolerability of Adjunctive KarXT in Subjects with Inadequately Controlled Symptoms of Schizophrenia

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]

Trial duration

12 Jun 2023 → 25 Mar 2026

Decision date (initial)

2024-08-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Karuna Therapeutics, Inc.

External identifiers

EU CT number

2024-510773-20-00

EudraCT number

2022-001666-35

ClinicalTrials.gov

NCT05304767

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Dose response, Therapy, Safety

To assess the long-term safety and tolerability of adjunctive KarXT in subjects with schizophrenia

Secondary objectives 5

1. To provide additional long-term safety data for monotherapy KarXT in subjects with schizophrenia
2. To compare the clinical effects (safety and efficacy) of monotherapy KarXT vs adjunctive KarXT after a randomized withdrawal of the background antipsychotic after 6 months of adjunctive therapy in subjects who are stable treatment responders
3. To evaluate cognition with the Cambridge Neuropsychological Test Automated Battery (CANTAB) in schizophrenia subjects with cognitive dysfunction
4. To assess steady-state plasma concentrations of xanomeline and trospium during treatment
5. To evaluate prolactin levels after administration of KarXT

Conditions and MedDRA coding

Schizophrenia

Regulatory references

Plan to share IPD

Yes

IPD plan description

Sponsor will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria, for Interventional Phase II-IV studies only

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Subject is aged 18 to 65 years (inclusive), at the time of randomization (Visit 3 of Study KAR-012)
2. Subject has successfully completed the treatment period (through Visit 8) of Study KAR-012
3. Subject has been compliant with the procedures in Study KAR-012 (in the Investigator's judgment)
4. Subject has been compliant with their background APD in Study KAR-012 in the opinion of the Investigator and based on subject and informant reporting. Note: Subjects are required to remain on the same appropriate approved APD as in Study KAR-012 and should stay on that same dose throughout the study
5. Subject is capable of providing signed ICF before any study assessments will be performed. Subject must be fluent in the language of the ICF to consent
6. Subject resides in a stable living situation, in the opinion of the Investigator
7. Subject has identified a reliable informant/caregiver willing and able to assist with study activities as needed throughout the subject's participation in the study. The informant does not have to be someone responsible for the subject’s physical or psychiatric well-being. As needed, the informant can complete the study visits assessments via phone (as .per local regulations). In Bulgaria, the informant needs to be physically present at all study visits where the Investigator determines that his/her input would be beneficial
8. 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 study drug. Sperm donation is not allowed for 30 days after the final dose of the study drug. 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 9

1. Risk for suicidal behavior during the study as determined by the Investigator's clinical assessment and/or C-SSRS at Visit 8 in Study KAR-012, as confirmed by the following: a. Subject answers "Yes" to "suicidal ideation" Item 4 (active suicidal ideation with some intent to act, without a specific plan) or Item 5 (active suicidal ideation with a specific plan and intent) on the C-SSRS b. Non-suicidal self-injurious behavior is not exclusionary
2. Any clinically significant abnormalities, including any finding(s) from the ECG, or laboratory test at Visit 6, and physical examination, vital signs, at the EOT visit of Study KAR-012 (Visit 8) that the Investigator, in consultation with the Medical Monitor, are considered to jeopardize the safety of the subject
3. Female subject is pregnant
4. 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 study requirements
5. Risk of violent or destructive behavior as per Investigator's judgment
6. Subjects participating in another investigational drug or device trial or planning on participating in another clinical trial during the study
7. History or high risk of urinary retention, gastric retention, or narrow angle glaucoma as evaluated by the Investigator
8. Subject is taking, or plans to take while in the study, any prohibited concomitant medication as outlined in APPENDIX 4
9. For all male subjects only, any one of the following: a. History of bladder stones b. History of recurrent urinary tract infections c. Serum prostate specific antigen >10 ng/mL d. An International Prostate Symptom Score (IPSS) of 5 (almost always) on either item 1, 3, 5, or 6 e. A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9 Note: IPSS will be required only for male subjects ≥ 45 years of age. An additional prostate-specific antigen (PSA) result prior to enrollment in study KAR-013 is not required; PSA results captured from the KAR-012 study will suffice.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of treatment-emergent adverse events (TEAEs)

Secondary endpoints 2

1. Incidence of serious TEAEs
2. Incidence of TEAEs leading to discontinuation of study drug

Investigational products

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

Test 4

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 10

Locations

1 EU/EEA country · 19 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 41 files

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

Application history

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