A Study of the Efficacy and Safety of SP-624 in the Treatment of Adults With Major Depressive Disorder

A Multi-center, Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy and Safety of SP-624 in the Treatment of Adults With Major Depressive Disorder

This is a Phase 2B clinical study evaluating the effectiveness and safety of SP-624 as compared to placebo in the treatment of adults with Major Depressive Disorder.

Study Overview

• Status: Active, not recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: SP-624; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 456
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Ima Clinical Research
    • Tucson, Arizona, United States, 85704
      • Noble Clinical Research
  • Arkansas
    • Bryant, Arkansas, United States, 72022
      • SanRo Clinical Research Group
  • California
    • Bellflower, California, United States, 90706
      • Clinical Innovations
    • Imperial, California, United States, 92251
      • Sun Valley Research Center
    • Lemon Grove, California, United States, 91945
      • Synergy San Diego
    • Oceanside, California, United States, 92056
      • Excell Research
    • Riverside, California, United States, 92506
      • CiTrials
    • Torrance, California, United States, 90504
      • Collaborative Neuroscience Research
    • Walnut Creek, California, United States, 94596
      • Sunwise Clinical Research
    • West Covina, California, United States, 91790
      • Next Level Clinical Trials
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • MCB Clinical Research Centers
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions
    • Lakeland, Florida, United States, 33803
      • Accel Clinical
    • Lauderhill, Florida, United States, 33319
      • Segal Trials
    • Miami Lakes, Florida, United States, 33016
      • Segal Trials - Miami Lakes
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions
    • Pinellas Park, Florida, United States, 33782
      • DMI Research
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Accelerated Enrollment Solutions
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Velocity Clinical Research
  • Illinois
    • Elgin, Illinois, United States, 60123
      • Revive Research Institute
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
  • Michigan
    • Bloomfield Hills, Michigan, United States, 48302
      • NeuroBehavioral Medicine Group
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • Midwest Research GRoup
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Alivation Research
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Ima Clinical Research
    • Las Vegas, Nevada, United States, 89119
      • Redbird Research
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center For Emotional Fitness
    • Marlton, New Jersey, United States, 08053
      • CenExel HRI
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Ima Clinical Research
  • New York
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials
    • New York, New York, United States, 10016
      • Pioneer Clinical Research
  • North Carolina
    • Cary, North Carolina, United States, 27511
      • Magnolia Clinical Research
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Chapel Hill
    • Charlotte, North Carolina, United States, 28211
      • New Hope Clinical Research
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Velocity Clinical Research
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
    • Middleburg Heights, Ohio, United States, 44130
      • North Star Medical Research
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Headlands
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions
  • Texas
    • Austin, Texas, United States, 78737
      • Donald J. Garcia, Jr, MD, PA
    • Dallas, Texas, United States, 75231
      • Future Search Trials of Dallas
    • El Paso, Texas, United States, 79902
      • Haracec Clinical Research
    • Richardson, Texas, United States, 75080
      • Pillar Clinical Research
    • Stafford, Texas, United States, 77477
      • R and H Clinical Research
    • Wichita Falls, Texas, United States, 76309
      • Grayline Research Center
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Everett, Washington, United States, 98201
      • Core Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Males and females, aged 18 to 65 years, inclusive.
• Meet DSM-5 criteria for moderate to severe MDD, as confirmed by the Mini International Neuropsychiatric Interview (MINI).
• In generally good physical health, in the opinion of the Investigator.
• Body mass index (BMI) must be ≥ 18 and ≤ 45 kg/m2.

Key Exclusion Criteria:

• Female who is pregnant, breastfeeding, or less than 6 months postpartum at screen.
• A history of or current DSM-5 diagnosis of MDD with psychotic features, any schizophrenia spectrum and other psychotic disorders, bipolar disorder, or personality disorder.
• Presence or history of any known clinically significant cardiovascular disorders including, but not limited to: coronary artery disease, heart failure, valvular heart disease, cardiomyopathies, myocardial infarction, chamber enlargement or hypertrophy, or orthostatic hypotension.
• Presence of uncontrolled hypertension, defined as consistent sitting systolic blood pressure (SBP) >160 mmHg or consistent sitting diastolic blood pressure (DBP) >95 mmHg despite present therapy.
• Screening laboratory value(s) outside the laboratory reference range that are considered to be clinically significant by the Investigator (clinical chemistry, hematology, thyroid function, and urinalysis).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SP-624; Participants to receive two 10 mg capsules of SP-624 once daily for a total daily dose of 20 mg	Drug: SP-624; Once daily oral administration of two capsules totaling 20 mg/day
Placebo Comparator: Placebo; Participant to receive 2 matching placebo capsules once daily	Drug: Placebo; Once daily oral administration of two matching placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score.	The MADRS is a 10-item depression rating scale used to assess the severity of depression. Individual items are scored on a 7-point scale (0 to 6). The toal score is the sum of individual items, ranging from 0 to 60; where a higher score indicates more depression.	Baseline to Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in the Clinical Global Impression - Severity (CGI-S) score.	The CGI-S is a 7-point scale to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. A score of 1 represents "normal" and 7 represents "most extremely ill".	Baseline to Weeks 1-4 and 1- and 2- Week Follow-up
Change from Baseline in Quick Inventory of Depressive Symptomology-Self-Report (QIDS-SR) total score.	The QIDS-SR is a 16-item self-reported scale where each item has a 4-point scale where 0 represents least impact scores while 3 represents greatest impact scores. Some questions are linked. The total score ranges from 0 to 27 where a higher score indicates more depression.	Baseline to Weeks 1-4 and 1- and 2- Week Follow-up
Change from Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score.	The MADRS is a 10-item depression rating scale used to assess the severity of depression. Individual items are scored on a 7-point scale (0 to 6). The toal score is the sum of individual items, ranging from 0 to 60; where a higher score indicates more depression.	Baseline to Weeks 1-3 and 1- and 2- Week Follow-up
Change from Baseline in 17-item-Hamilton Depression Rating Scale (HAM-D-17) total score.	The 17-item HAM-D is used to assess the severity of depression. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=No difficulty/absent and 4=most severe. The total score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression.	Baseline to Weeks 2 and 4
Change from Baseline in Sheehan Disability Scale (SDS) total score.	The SDS is a 3-part scale that measures the degree of disruption on work, social and family life using an 11-point scale where 0 represents "no disruption" and 10 represents "extreme disruption". In addition to the 11-point scale, participants are asked to indicate the number of days in the past week that were "lost" and numbers of days that were "underproductive". The results of these questions have a range from 0 to 7. A total global functioning impairment score can be utilized by summing the scores from work, social and family life scales for a value range from 0 to 30.	Baseline to Weeks 2 and 4
Change from Baseline in Symbol Digit Modalities Test (SDMT) score.	The SDMT is an assessment of complex scanning and visual tracking requiring elements of attention, visuoperceptual processing, working memory, and cognitive/psychomotor speed. The SDMT measures the time to pair abstract symbols with specific numbers. The number of correct substitutions within 90 seconds is recorded and the total score is derived from the total number of correct responses with a minimum possible score of 0 and maximum of 110 where high scores indicate better outcome.	Baseline to Weeks 2 and 4
Incidence rates of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and TEAEs leading to withdrawal from study.		Baseline to Weeks 1-4 and 1- and 2- Week Follow up

Collaborators and Investigators

• Sponsor: Sirtsei Pharmaceuticals, Inc.
• Collaborators: Rho, Inc.
• Investigators: Study Director: Greg Rigdon, PhD, Sirtsei Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Raskin J, Clayton AH, Kornstein SG, Papakostas GI, Prescott Y, Abernathy K, Hall J, Ackermann M, Wargin W, Rigdon G; SP-624-201 study investigators. A phase 2, multicenter, double-blind, randomized, placebo-controlled study of the safety and efficacy of forvisirvat (SP-624) in the treatment of adults with major depressive disorder. Curr Med Res Opin. 2025 Sep;41(9):1723-1734. doi: 10.1080/03007995.2025.2574465. Epub 2025 Oct 29.

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2024
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): July 15, 2026

Study Registration Dates

• First Submitted: February 2, 2024
• First Submitted That Met QC Criteria: February 2, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: SP-624-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No