IRL757 for Parkinson's disease | Apathy

Inclusion criteria

• {"criterion_text":"- Male and female participants between 50 and 90 years of age, inclusive, with diagnosed Parkinson’s disease according to the Movement Disorders Society Clinical Diagnostic Criteria for Parkinson's disease.\n- Hoehn and Yahr stage ≤ 4 at screening.\n- MoCA score of 20 or greater at screening and baseline.\n- Meets the ISCTM definition of apathy (criterion B), defined as exhibiting ≥ 1 symptom in ≥ 2 of the following 3 dimensions, that is persistent or frequently recurrent (ie, ≥ 3 days per week) for ≥ 4 weeks prior to screening: • Diminished initiative (less spontaneous and/or active than usual self; less likely to initiate usual activities such as hobbies, chores, self-care, conversation, work-related or social activities), • Diminished interest (less enthusiastic about usual activities, less interested in, or less curious about, events in their environment, less interested in activities and plans made by others, less interested in friends and family, less persistence in maintaining or completing tasks or activities), or • Diminished emotional expression/responsiveness (less spontaneous emotions, less affectionate compared to their usual self, expresses less emotion in response to positive or negative events, less concerned about the impact of their actions on other people, less empathy). The symptoms must represent a significant change from the participant’s usual behaviour and cause significant impairment in personal, social, or occupational functioning. Finally, the symptoms must not be due to psychiatric illness, intellectual disability, physical/motor disabilities, or changes in level of consciousness or the effects of substances.\n- Participants with moderate to severe apathy based on a score of at least −16 on the LARS at screening and baseline.\n- Availability of the primary caregiver, who spends greater than 10 hours a week with the participant and supervises his or her care, to accompany the participant to trial visits and to participate in the trial.\n- Treatment with anti-Parkinson drugs, antidepressants (except for those listed as prohibited medications in Section 6.6.1), and ChEIs is permitted if doses are stable for 1 month before randomization and remain stable during the trial."}

Exclusion criteria

• {"criterion_text":"- Any active, current psychiatric comorbidity (such as major depressive disorder, obsessive-compulsive disorder, etc) a) as assessed by the MINI at screening. b) as assessed by the MADRS at the baseline visit with a score > 18.\n- Significant communicative impairments that prohibit meaningful participation in the trial assessments.\n- Central nervous system abnormalities (eg, cerebral aneurysm) and/or other vascular abnormalities such as vasculitis or pre-existing stroke, motor tics, or family history or diagnosis of Tourette's syndrome, seizures (convulsions, epilepsy), or historical clinically significant abnormal electroencephalograms (EEGs).\n- History of cancer within 5 years prior to screening, with the following exceptions: adequately treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate cancer, or in situ cervical cancer. The cancer must not be active or currently under treatment except for potentially long-term stable medications.\n- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.\n- Any planned major surgery within the duration of the trial.\n- Any positive result at screening for serum hepatitis B surface antigen, hepatitis C antibody, or HIV.\n- Any vital signs values outside of the following ranges after 10 minutes of supine rest at the time of screening: a) Systolic blood pressure (SBP) > 150 mmHg b) Diastolic blood pressure (DBP) > 90 mmHg c) Heart rate < 50 or > 100 beats per minute.\n- Participants with a history of hypertension must have stable blood pressure for the 3 months prior to the trial, defined as blood pressure < 150/90 mmHg. If this criterion is not met the participant is not eligible for the trial.\n- Prolonged QT interval corrected for heart rate using Fridericia’s formula (QTcF) > 450 msec for male participants or > 470 msec for female participants, cardiac arrhythmias, or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the investigator.\n- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to IRL757.\n- Score of > 2 in the MDS-UPDRS Part 1, Question 1.2 (hallucinations and psychosis).\n- Current nicotine use; irregular nicotine use less than 3 times per week is allowed before the screening visit.\n- Positive screen for illicit drugs (including cannabinoids) and/or abuse or positive screen for alcohol at screening or on Day 1 prior to administration of the IMP.\n- Use of anabolic steroids.\n- Use of antipsychotics.\n- The participant is unwilling or unable to discontinue taking alpha-2 adrenergic receptor antagonists and/or cytochrome P450 (CYP) inhibitor or substrate drugs at least 14 days or 5 times the half-life of the drug (whichever is longer) before randomization (see Table 6.6.1-1).\n- Excessive or variable daily caffeine consumption (ie, exceeding 3 cups per day) for the 2 weeks prior to screening.\n- Plasma donation within 1 month of screening or any blood donation/blood loss > 450 mL during the 3 months prior to screening\n- Participants who are breastfeeding.\n- Participants who have a positive pregnancy test result prior to receiving IMP.\n- Heterosexually active participants of reproductive potential (PORP) / POCBP who do not agree to use a highly effective method of birth control or remain fully abstinent from sexual activity with the potential for conception, per the guidelines in Section 10.3. Female participants of nonchildbearing potential (permanently sterilized [ie, hysterectomy, bilateral oophorectomy], postmenopausal for at least 12 months, or otherwise incapable of pregnancy) and male participants who have had a bilateral orchiectomy are eligible for enrolment\n- Need for acute psychiatric hospitalization.\n- Participants who do not agree to refrain from donating sperm or eggs from trial screening through 90 days (for sperm) and 30 days (for eggs) after the last dose of IMP.\n- Participants who have participated in a clinical trial involving an investigational drug or device within the last 90 days or who participated in more than 2 clinical trials involving an investigational drug or device within the past year.\n- The investigator considers the participant unlikely to comply with trial procedures, restrictions, and requirements.\n- Any condition that, in the opinion of the investigator, makes it medically inappropriate or risky for the participant to enrol in the trial.\n- Participants who: a) Answer “Yes” on the C-SSRS Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) within the last 6 months prior to screening or the baseline visit, OR b) Answer “Yes” on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) within the last 6 months prior to screening or at the baseline visit, OR c) Answer “Yes” on any of the 5 C-SSRS Suicidal Behaviour Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behaviour) within 2 years prior to screening or at the baseline visit, OR d) In the opinion of the investigator, present a serious risk of suicide.\n- Subthalamic stimulation of less than 1 year from screening.\n- Subthalamic stimulation without stable parameters for 3 months from screening.\n- Clinically significant impulse control disorders (ICDs) as assessed by the QUIP-RS (score > 6).\n- Renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73m2 calculated based on cystatin C).\n- Moderately impaired hepatic function or advanced hepatic dysfunction as assessed by a Child-Pugh score B or C."}

Primary endpoints

• {"endpoint_text":"- Frequency, seriousness, and severity of AEs; change from baseline in physical examinations, clinical laboratory tests, vital signs, ECGs, C-SSRS, the QUIP-RS, and daytime sleepiness (ESS)","definition_or_measurement_approach":"Adverse events characterised by frequency, seriousness and severity; clinical safety measures assessed as change from baseline in physical examinations, laboratory tests, vital signs, ECGs and validated scales (C-SSRS for suicidality, QUIP-RS for impulse control, ESS for daytime sleepiness)."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in: • NPI-C (apathy domain) • LARS","definition_or_measurement_approach":"Change from baseline in neuropsychiatric inventory-clinician (NPI-C) apathy domain score and Lille Apathy Rating Scale (LARS) score."}

Methods

• Healthcare professional referrals and Dr-to-Dr letters (site outreach to neurologists/clinics).
• Site-based materials: posters, brochures, study visit guides and GP letters distributed at participating sites.
• Patient and caregiver materials: brochures, flowcharts and subject ID cards for distribution to patients and caregivers.
• Patient advocacy engagement: materials for Patient Advocacy Groups (PAG) including clinical trial listings, e-newsletter content and site-to-PAG intro letters.
• Digital channels: social media ads, email blasts, e-newsletters and online clinical trial listings.
• Chart review and HCP referral flyers to identify potential participants.

Bulgaria

Earliest CTIS Part Ii Submission Date

08-12-2025

Latest Decision Or Authorization Date

12-12-2025

Processing Time Days

4

Number Of Sites

4

Number Of Participants

35

Germany

Earliest CTIS Part Ii Submission Date

10-12-2025

Latest Decision Or Authorization Date

12-02-2026

Processing Time Days

64

Number Of Sites

3

Number Of Participants

20

Poland

Earliest CTIS Part Ii Submission Date

05-12-2025

Latest Decision Or Authorization Date

22-12-2025

Processing Time Days

17

Number Of Sites

7

Number Of Participants

35

Spain

Earliest CTIS Part Ii Submission Date

01-12-2025

Latest Decision Or Authorization Date

22-12-2025

Processing Time Days

21

Number Of Sites

4

Number Of Participants

35

Primary sponsor

Full Name

Integrative Research Laboratories Sweden AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

Syneos Health Clinique Inc.

Responsibilities

Sponsor duties codes: 4

Name

Syneos Health Inc.

Responsibilities

Sponsor duties codes: 4

Name

Syneos Health UK Limited

Responsibilities

Multiple sponsor duties including Patient Recruitment and IDMC oversight (code 15) and other operational codes (1,2,5-13).

Name

Suvoda LLC

Responsibilities

Sponsor duties codes: 3

Third parties

• {"country":"Sweden","full_name":"Lablytica Life Science AB","duties_or_roles":"PK analysis","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Syneos Health Clinique Inc.","duties_or_roles":"Sponsor duties codes: 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"Sponsor duties codes: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Sponsor duties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"P1vital Products Limited","duties_or_roles":"Sponsor duties code 15 (grip strength)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Syneos Health UK Limited","duties_or_roles":"Sponsor duties codes: 1,10,11,12,13,2,5,6,7,8,9 and code 15 (Patient Recruitment and IDMC oversight)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Labor Dr. Wisplinghoff GbR","duties_or_roles":"Sponsor duties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"LabConnect GmbH","duties_or_roles":"Sponsor duties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Cambridge Cognition Limited","duties_or_roles":"Sponsor duties code 15 (CANTAB & Speech Analysis)","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"LabConnect Europe B.V.","duties_or_roles":"Sponsor duties code 15 (Kit Production)","organisation_type":"Laboratory/Research/Testing facility"}