First in Human Study in Subjects With Obesity, But Otherwise Healthy

A Phase 1, Randomized, Placebo-Controlled, Double-Blind First in Human, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of DA-1726 in Participants With Obesity.

This is a First in Human study to evaluate the safety and tolerability of DA-1726 following single and multiple doses in participants with obesity, but otherwise healthy subjects.

Study Overview

• Status: Recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: DA-1726; Drug: Placebo to DA-1726

Detailed Description

This is a Phase 1, randomized, placebo-controlled, double-blind, sequential parallel group study to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple ascending doses of DA-1726 in adult participants (aged 18 to 65 years) with obesity (BMI ≥30 - 45 kg/m2). DA-1726 will be administered via subcutaneous (SC) injection within the clinic setting.

• Study Type: Interventional
• Enrollment (Estimated): 81
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Robert Homolka, MS; Phone Number: 8572991038; Email: CRinfo@Neurobopharma.com
• Study Contact Backup: Name: Ji Eun Lee, PharmD; Phone Number: 8572991038; Email: CRInfo@Neurobopharma.com

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Recruiting
      • Clinical Pharmacology of Miami, LLC
      • Contact: Alexander N Prezioso, MD; Phone Number: 201-320-6446; Email: aprezioso@ergclinical.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Willing and able to provide informed consent prior to initiation of any study specific procedures/activities.
2. Males and females ≥18 to <=65 years of age, at the time of signing informed consent, who have been diagnosed with obesity, or have signs/symptoms consistent with obesity.
3. Except for obesity, otherwise healthy as determined by the investigator based on a medical evaluation including physical exam, medical history, laboratory tests, and ECGs.
4. Body mass index (BMI) ≥ 30 kg/m2 to 45 kg/m2 (Obesity to be confirmed by Caliper test).
5. Has maintained a stable body weight during the 3 months prior to Screening (<5% body weight change).

6. Willing to maintain current diet and physical activity regimen.

   • SAD Cohorts (Be willing to eat a standard diet while in the Clinical Research Unit).
   • MAD Cohorts (Be willing to eat a standard diet while in the Clinical Research Unit). If appetite decreases, participants may not maintain their current diet.

7. Females must be of non-reproductive potential:

   • Postmenopausal defined as:

     • Age of ≥55 years with no menses for at least 12 months; OR
     • Age <55 years with no menses for at least 12 months AND with a follicle-stimulating hormone level >40 IU/L or according to the definition of "postmenopausal range" for the laboratory involved; OR
   • History of hysterectomy; OR
   • History of bilateral oophorectomy
   • History of tubal ligation (surgically sterile)
8. Males must agree to practice an acceptable method of effective birth control while on study through 5 half-lives plus one week after receiving last dose of DA-1726.

Acceptable methods of birth control include:

• Sexual abstinence
• Vasectomy and testing that shows there are no sperm in semen.
• Condom with spermicide (male) in combination with barrier methods (diaphragm, cervical cap, or cervical sponge), hormonal birth control, or IUS (females)

Exclusion Criteria:

1. History or clinical evidence of diabetes mellitus, including a fasting glucose of ≥ 120 mg/dL and/or HbA1c ≥ 6.5% at Screening.
2. Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2).
3. History of cholecystectomy < 6 months prior to screening.
4. Subjects with screening calcitonin level of ≥15 pg/mL (calcitonin levels will be monitored during the study).
5. Triglycerides ≥500 mg/dL at Screening.
6. History of pancreatitis.

7. Have a medical history or current evidence of clinically significant cardiac condition as evidenced by any of the following at Screening or check-in:

   • QTc at Screening from locally generated data of >450 msec in males or >470 msec in females or history of long QT syndrome
   • Supine systolic BP higher than 150 mmHg and a supine diastolic BP higher than 95 mmHg at Screening or check-in
   • Supine HR of <50 or >100 beats per minute on 2 of 3 triplicate ECGs at Screening or check-in
   • Heart block of the 1st, 2nd, or 3rd degree
   • Sick sinus syndrome (irregular heartbeat patterns)
   • Disorders in cardiac conduction
   • Peripheral blood circulation issues
   • Heart valve conditions
   • Cardiomyopathy
   • History of myocardial infarction
   • Unstable angina
   • History of heart artery bypass surgery
   • History of stroke
   • History of heart failure
8. Regular consumption of caffeine-containing beverages, including coffee, tea, energy drinks, and caffeinated sodas, exceeding 3 cups per day.
9. Current use of tobacco products or having a history of tobacco use within the past 6 months.
10. Have significant previous or current history of comorbidities capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the investigational product; or of interfering with the interpretation of data.
11. History of GI abnormality that could affect GI motility (including small bowel or colonic resection, inflammatory bowel disease, irritable bowel syndrome, gastroparesis [clinically significant gastric emptying abnormality], and colon / GI tract cancer).
12. Have a history of chronic medical conditions involving the heart, liver, or kidneys (e.g., atherosclerotic coronary vascular disease (ASCVD), heart failure, liver cirrhosis, chronic kidney disease).
13. Untreated or uncontrolled hypo/hyperthyroidism defined as thyroid-stimulating hormone >6 mIU/L or <0.4 mIU/L.
14. Obesity that was induced by other endocrinologic disorders (e.g., Cushing's Syndrome).
15. Evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies.
16. Evidence of hepatitis C and/or positive hepatitis C antibody and hepatitis B, hepatitis B core antibody, and/or positive hepatitis B surface antigen.
17. Have a history or presence of psychiatric disorders that would present a safety risk or may significantly impair the participant's ability to comply with study procedures.
18. Any lifetime history of a suicidal attempt or any suicidal behavior, as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS).
19. History of malignancy of any type, other than basal cell carcinoma, occurring less than 5 years prior to randomization.
20. History of substance abuse (i.e., alcohol or illicit substances) within 12 months prior to Screening; and/or a positive test for alcohol/drugs of abuse at Screening.
21. Previous surgical treatment for obesity or any form of bariatric surgery.
22. Currently receiving treatment in another investigational drug or device study or 5 half lives or 30 days since last dose of investigational drug, whichever is longer.
23. Participants with a history of significant allergic or drug reactions (NSAIDs or antibiotics) or known allergy to DA 1726 excipients that would place them at increased risk.
24. Have received any vaccine ≤30 days prior to check-in.
25. Albumin level <3.5 g/dL (<35 g/L) at Screening.
26. Aspartate aminotransferase (AST) ≥1.25 × upper limit of normal (ULN) at Screening.
27. Alanine aminotransferase (ALT) ≥1.25 × upper limit of normal (ULN) at Screening.
28. Bilirubin >1.25 upper limit of normal (ULN) at Screening.
29. Absolute neutrophil count <lower limit of normal (LLN) at Screening.
30. Estimated glomerular filtration rate of ≤60 mL/min for women and men (based on the Chronic Kidney Disease Epidemiology Collaboration equation) at the Screening.
31. Fasting low-density lipoprotein ≥160 mg/dL at Screening.
32. Hemoglobin <LLN at Screening.
33. Platelet count <LLN at Screening.

34. Current or history of treatment with medications that may cause significant weight gain, within 3 months of Screening, including:

    • Systemic corticosteroids (except for a short course of treatment, i.e., 7-10 days)
    • Tricyclic antidepressants
    • Atypical antipsychotics
    • Mood stabilizers (e.g., imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium)
    • Antidiabetic Medications (e.g., insulin or certain sulfonylureas, that may lead to weight gain)
    • Beta-blockers (e.g., the ones used to treat conditions like hypertension that may cause weight gain)
    • Antihistamines (particularly the first-generation ones, that may have sedative effects and could potentially contribute to weight gain)
    • Contraceptives
    • Any non-steroidal anti-inflammatory drugs
35. Current participation (or within the last 3 months) in an organized weight reduction program or currently using or has used within 3 months prior to Screening: pramlintide, sibutramine, orlistat, zonisamide, topiramate, phentermine, naltrexone, lorcaserin, liraglutide, semaglutide, tirzepatide or metformin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Part 1 - Single Ascending Dose; Single doses of DA-1726 in adult participants (aged 18 to 65 years) with obesity (BMI ≥30 - 45 kg/m2). DA-1726 will be administered via subcutaneous (SC) injection within the clinic setting.	Drug: DA-1726; Active; Drug: Placebo to DA-1726; Placebo
Placebo Comparator: Part 2 - Multiple Ascending Dose; Multiple doses of DA-1726 in adult participants (aged 18 to 65 years) with obesity (BMI ≥30 - 45 kg/m2). DA-1726 will be administered via subcutaneous (SC) injection within the clinic setting.	Drug: DA-1726; Active; Drug: Placebo to DA-1726; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	AEs, SAEs, TEAEs and AEs leading to treatment discontinuation.	From date of randomization (baseline) until the discontinuation or completion, whichever came first, assessed up to 26 Days for Part 1 and 47 Days for Part 2.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic	PK profile of DA-1726 serum concentrations of DA-1726 over time.	From date of randomization (baseline) until the discontinuation or completion, whichever came first, assessed up to 26 Days for Part 1 and 47 Days for Part 2.
Immunogenicity	Measurement of anti-drug antibodies and neutralizing antibodies at baseline and at identified points during the study.	From date of randomization (baseline) until the discontinuation or completion, whichever came first, assessed up to 26 Days for Part 1 and 47 Days for Part 2.

Collaborators and Investigators

• Sponsor: NeuroBo Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2024
• Primary Completion (Estimated): December 14, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: January 9, 2024
• First Submitted That Met QC Criteria: February 7, 2024
• First Posted (Actual): February 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: DA-1726-1001

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
• product manufactured in and exported from the U.S.: No