A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Study of ALA-3000, Evaluating the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy in Subjects With Treatment-Resistant Depression (TRD)

Plain English Summary

Multiple Ascending Dose Phase 1 Study of ALA-3000 is a Phase 1 clinical trial sponsored by Alar Pharmaceuticals Inc. studying Treatment Resistant Depression. This study tests a new drug called ALA-3000 for adults with depression that hasn't responded to other treatments. It's for individuals aged 18-65 who have tried at least two antidepressant medications without success. Participants will receive either ALA-3000 or a placebo via injection, and may also start a new oral antidepressant. Alternative treatments include other medications, psychotherapy, and brain stimulation therapies like ECT. The trial aims to enroll 37 participants.

Official 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

Here is what you need to know about eligibility for this trial. You can join if you are between 18 and 65 years old and have been diagnosed with major depression that hasn't improved with at least two previous treatments. You cannot join if you have certain other mental health conditions (like bipolar disorder or psychosis), significant heart or liver problems, or have had recent suicidal thoughts or behaviors. You must be medically stable and willing to use reliable contraception if you are of childbearing potential. This trial is studying Treatment Resistant Depression, so participants generally need a confirmed diagnosis.

What They're Measuring

The study will measure how safe ALA-3000 is by tracking any side effects, abnormal vital signs (blood pressure, heart rate, breathing), and changes in blood oxygen levels. The specific primary outcome measures are: Incidence of treatment-related adverse events (AEs) (Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit); Incidence of abnormal orthostatic blood pressure (Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit); Incidence of abnormal heart rate (Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit); Incidence of abnormal blood oxygen saturation (pulse oximetry) (Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit); Incidence of abnormal respiratory rate (Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial is important because it explores a new potential treatment for treatment-resistant depression, a condition that significantly impacts patients' lives and for which current options are limit This research targets Treatment Resistant Depression, where improved treatment options are needed.

Investor Insight

This Phase 1 study is an early step to assess a new drug for a large market of patients with unmet needs, indicating potential for future development if safety and preliminary efficacy are demonstrate Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of ALA-3000, what to expect during the study visits, and how it might interact with other medications. Participation involves regular clinic visits for injections, physical exams, blood tests, and questionnaires to monitor your health and depression symptoms. You will need to use effective birth control during the study and for a period afterward if you are of childbearing potential. The trial is being conducted at 4 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 37 participants

Interventions

• DRUG: ALA-3000 — Subcutaneous injection
• DRUG: Placebo — Subcutaneous injection
• DRUG: escitalopram, sertraline, duloxetine or venlafaxine XR — Newly initiated oral AD selected from SSRI (escitalopram or sertraline) or SNRI (duloxetine or venlafaxine XR) will be given daily

Primary Outcomes

• Incidence of treatment-related adverse events (AEs) (Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit)
• Incidence of abnormal orthostatic blood pressure (Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit)
• Incidence of abnormal heart rate (Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit)
• Incidence of abnormal blood oxygen saturation (pulse oximetry) (Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit)
• Incidence of abnormal respiratory rate (Baseline (prior to dosing) through the End of Study (Day 36)/Early termination or Follow up visit)

Secondary Outcomes

• Cmax for each dosing (Up to 28 days post last dose)
• Tmax for each dosing (Up to 28 days post last dose)
• AUCs for each dosing (Up to 28 days post last dosing)
• t1/2 (Up to 28 days post last dosing)

Full Eligibility Criteria

Inclusion Criteria:

1. 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.
2. 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).
3. 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.
4. 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.
5. Subject has a MADRS total score of ≥ 22 at screening.
6. 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.
7. Female subjects of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) at screening visit and a negative urine pregnancy test prior to SC administration on Day 1.
8. 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.
9. Agree to adhere to the prohibitions and restrictions specified in this protocol.

Exclusion Criteria:

1. 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.
2. 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.
3. Subject has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2 × the upper limit of normal (ULN) or total bilirubin \> 1.5 × ULN.
4. 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.
5. 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.
6. 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.
7. Subject has a score of ≥ 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.
8. Subjects who meet DSM-5 criteria for moderate or severe substance or alcohol use disorder, except for nicotine or caffeine, within 6 

Trial Locations

• Pillar Clinical Research, Little Rock, Arkansas, United States
• Arch Clinical Trials, St Louis, Missouri, United States
• Clinilabs Drug Development Corporation, Eatontown, New Jersey, United States
• Neuro-Behavioral Clinical Research, Inc, North Canton, Ohio, United States

Frequently Asked Questions

Related Conditions

• Depression
• Major Depressive Disorder
• Treatment-Resistant Depression
• Mood Disorders
• Anxiety Disorders
• Bipolar Disorder
• Psychotic Disorders
• Neurological Disorders
• Mental Health
• Psychiatry

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