Multiple Ascending Dose Phase 1 Study of ALA-3000 (NCT06965569) | Clinical Trial Compass
CompletedPhase 1
Multiple Ascending Dose Phase 1 Study of ALA-3000
United States37 participantsStarted 2025-04-21
Plain-language summary
This is a randomized, double-blind, placebo-controlled, multiple-dose study of ALA-3000 designed to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy in subjects with treatment-resistant depression (TRD).
Who can participate
Age range18 Years β 65 Years
SexALL
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Inclusion criteria
β. Male or female subject aged between 18 and 65 at screening visit and is able to provide informed consent prior to initiation of any study related procedures.
β. At screening visit, subjects meet Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) criteria for single-episode major depressive disorder (MDD) or recurrent MDD, without psychotic features, based upon clinical assessment and confirmed by the Mini International Neuropsychiatric Interview (MINI).
β. Subject is medically stable on basis of physical examination, medical history, vital signs (blood pressure, pulse rate, respiration rate, blood oxygen saturation, and temperature), clinical laboratory tests, and 12-lead ECG performed at screening visit, and/or prior to SC administration on Day 1. Subjects with abnormalities that are judged to be not clinically significant (NCS) at the discretion of the investigator may be included. This determination must be recorded in the subject's source documents and initialed by the investigator.
β. At screening visit, subjects must have insufficient response to at least 2 oral AD treatments, at least one of which is in the current episode of depression. Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ) will be used to assess AD treatment response during the current episode; prior medication history (e.g., medical/pharmacy/prescription records or a letter from a treating physician, etc.) will be used to determine AD treatment response in prior episode(s). If the subject's current episode of depression is \> 2 years, the upper limit of duration for assessing treatment response is applicable to only the last 2 years.
β. Subject has a MADRS total score of β₯ 22 at screening.
β. Male and female subjects of childbearing potential must be willing to use a reliable method of contraception (e.g., total abstinence, condom and spermicide, intrauterine device \[IUD\], oral contraception which has been stable for 30 days) during the entire trial and at least 4 months after stopping the investigational product.
β. Female subjects of childbearing potential must have a negative serum Ξ²-human chorionic gonadotropin (Ξ²-hCG) at screening visit and a negative urine pregnancy test prior to SC administration on Day 1.
Exclusion criteria
β. Subject has a history of, or current signs and symptoms of, liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, metabolic disturbances, or fibromyalgia.
β. Subject has uncontrolled hypertension despite diet, exercise or a stable dose of a permitted anti-hypertensive treatment at screening visit, or prior to SC administration on Day 1 (defined as a supine SBP \> 140 mmHg or DBP \> 90 mmHg); or any past history of hypertensive crisis.
β. Subject has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) β₯ 2 Γ the upper limit of normal (ULN) or total bilirubin \> 1.5 Γ ULN.
β. Subjects with history of or current DSM-5 diagnosis of psychotic disorder, or MDD with psychotic features, post-traumatic stress disorder (PTSD), bipolar or related disorders (confirmed by MINI), obsessive compulsive disorder (current only), intellectual disability (DSM-5 diagnostic codes 317, 318.0, 318.1, 318.2, 315.8, and 319), autism spectrum disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder.
β. Subject has suicidal ideation with intent to act within 6 months prior to screening visit or Study Day 1 (predose) based on investigator's discretion or C-SSRS, or has a history of suicidal behavior within the past year as assessed on the C-SSRS; or subject has homicidal ideation/intent at screening visit or on Day 1.
β. Subject had previously no treatment response to ketamine, S-ketamine, R-ketamine, all of the available AD treatment options in the double-blind phase (based on MGH-ATRQ), or an adequate course of electroconvulsive therapy (defined as at least 7 treatments with unilateral/bilateral electroconvulsive therapy \[ECT\]), in the current major depressive episode according to clinical judgment.
β. Subject has a score of β₯ 5 on the STOP-Bang questionnaire, in which case obstructive sleep apnea must be ruled out (e.g., apnea-hypopnea index \[AHI\] must be \< 30). A subject with obstructive sleep apnea can be included if he or she is using a positive airway pressure device or other treatment/therapy that is effectively treating (i.e., AHI \< 30) his or her sleep apnea.
What they're measuring
1
Incidence of treatment-related adverse events (AEs)
Timeframe: Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit
2
Incidence of abnormal orthostatic blood pressure
Timeframe: Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit
3
Incidence of abnormal heart rate
Timeframe: Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit
4
Incidence of abnormal blood oxygen saturation (pulse oximetry)
Timeframe: Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit
5
Incidence of abnormal respiratory rate
Timeframe: Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit
6
Incidence of abnormal body temperature
Timeframe: Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit
7
Incidence of abnormal 12-lead electrocardiogram (ECG) parameters
Timeframe: Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit
β. Male and female subjects must agree not to donate sperm or eggs (ova, oocytes) during the study and for at least 3 months after receiving the investigational drug.
β. Subjects who meet DSM-5 criteria for moderate or severe substance or alcohol use disorder, except for nicotine or caffeine, within 6 months prior to screening visit.
8
Incidence of abnormal hematologic findings
Timeframe: Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit
9
Incidence of abnormal serum chemistry test result
Timeframe: Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit
10
Incidence of abnormal urine test result
Timeframe: Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit
11
Incidence of abnormal urine cytologic findings
Timeframe: Baseline (prior to dosing) and the End of Study (Day 36) visit
12
Incidence and severity of dissociative symptoms assessed by Clinician Administered Dissociative States Scale (CADSS)
Timeframe: Baseline (prior to dosing) through the End of Study (Day 36)
13
Incidence and severity of treatment-emergent sedation assessed by Modified Observer's Assessment of Alertness/ Sedation (MOAA/S)
Timeframe: Baseline (prior to dosing) through the End of Study (Day 36)
14
Incidence and severity of potential withdrawal symptoms assessed by Physician Withdrawal Checklist; 20-item (PWC-20)
Timeframe: Two weeks after last investigational product administration and through the End of Study (Day 36)/Early termination or Follow up visit
15
Incidence and severity of suicide ideation assessed by Columbia Suicide Severity Rating Scale (C-SSRS)
Timeframe: Baseline (prior to dosing) and through the End of Study (Day 36)/Early termination or Follow up visit
16
Incidence and severity of four-item positive symptom subscale of the Brief Psychiatric Rating Scale (BPRS+)
Timeframe: Baseline (prior to dosing) and through the End of Study (Day 36)/Early termination
17
Injection site tolerability based on injection site grading scale
Timeframe: At the time of injection and through the End of Study (Day 36)/Early termination or Follow up visit
18
Injection site tolerability based on injection site pain visual analog scale (VAS)
Timeframe: At the time of injection and through the End of Study (Day 36)/Early termination or Follow up visit
19
Injection site tolerability based on injection site evaluation for potential reactions and evidence of removal
Timeframe: At the time of injection and through the End of Study (Day 36)/Early termination or Follow up visit