Clinical trial NCT06577090: Study to Evaluate the Effect on Obesity of Once Weekly Nimacimab Injection and Once Weekly Nimacimab Injection Co-administered With Semaglutide Injection Versus Placebo
Official title: A Phase 2 Study of Once Weekly Nimacimab Injection, Compared to Placebo Injection and Once Weekly Nimacimab Injection Co-administered With Semaglutide Injection in Participants Who Are Overweight or Obese
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Obesity
Lead sponsor: Skye Bioscience, Inc.
Sponsor class: INDUSTRY
First posted: 2024-08-29
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a proof-of-concept study to assess the safety and efficacy of Nimacimab Injection compared to an active and placebo injection control.

Detailed description: The purpose of this study is to measure the change in body weight with once weekly doses of Nimacimab Injection compared with placebo injection and once weekly Nimacimab Injection co-administered with commercially available semaglutide injection (Wegovy®) in participants with obesity or are overweight with weight-related comorbidities.

Eligibility criteria: Inclusion Criteria:

1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Participants must be at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place to 65 years, inclusive, at the time of signing the informed consent.
3. Male, female, and/or nonbinary participants.
4. Have Body Mass Index (BMI) of

   1. ≥ 30 kg/m2 to ≤ 45 kg/m2 OR
   2. ≥ 27 kg/m2 and \< 30 kg/m2 with clinically confirmed diagnosis of at least 1 of the following weight-related co-morbidities:

   i. dyslipidemia: on lipid-lowering medication or having low-density lipoprotein (LDL) ≥ 160 mg/dL (4.1 mmol/L) or triglycerides ≥ 150 mg/dL (1.7 mmol/L) or high-density lipoprotein (HDL) \< 40 mg/dL (1.0 mmol/L) for men or HDL \< 50 mg/dL (1.3 mmol/L) for women at screening.

   ii. cardiovascular disease: (for example, ischemic cardiovascular disease, New York Heart Association \[NYHA\] Functional Classification Class I-II heart failure).

   iii. obstructive sleep apnea syndrome (Salzano 2021).

   iv. controlled arterial hypertension with systolic blood pressure (SBP) \< 150 mmHg or diastolic blood pressure (DBP) \< 90 mmHg.
5. Have an HbA1c \<6.5% at screening.
6. Have had a stable body weight for the 3 months prior to screening (no more than 5% body weight gain and/or loss).
7. If on cardiovascular, anti-hypertensive, must be controlled controlled on a stable dose for 3 months prior to randomization.
8. If on hormone replacement therapy, must be on a stable dose for at least 3 months prior to screening, including use of thyroxine.
9. Females of childbearing potential must agree:

   1. to use an approved method of contraception from screening throughout the study and for at least 90 days after the last dose of study drug.
   2. to not donate ova from screening throughout the study and for at least 90 days after the last dose of study drug.
   3. have a negative pregnancy test at screening and Day 0.
10. Male participants who are (hetero) sexually active must agree that he and his partner will each use an approved method of contraception from screening throughout the study and for at least 90 days after the last dose of study drug.
11. Agreement in male participants to not donate sperm from screening throughout the study and for at least 90 days after the last dose of study drug.

Exclusion Criteria:

1. Have any prior diagnosis of type 1 or type 2 diabetes mellitus (T1DM or T2DM, or rare forms of diabetes mellitus).
2. Have at least 1 laboratory value suggestive of diabetes during screening, including 1 or more of HbA1c ≥ 6.5% (48 mmol/mol), fasting serum glucose ≥ 126 mg/dL (7.0 mmol/L), or random glucose ≥ 200 mg/dL (11.1 mmol/L).
3. Have a prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty, if performed \> 1 year prior to screening).
4. Have obesity induced by other disorders (for example, Cushing's syndrome) or diagnosed monogenetic or syndromic forms of obesity (for example, Melanocortin 4 Receptor deficiency or Prader-Willi Syndrome) or use of systemic corticosteroids or uncontrolled hypothyroidism. (Hypothyroidism on stable treatment is allowed if thyroid stimulating hormone (TSH) measure within the last 3 months of screening is within normal limits).
5. Have had at any time or plan to have endoscopic and/or device-based therapy for obesity including but not limited to the following:

   1. Mucosal ablation,
   2. Gastric artery embolization,
   3. Intragastric balloon, OR
   4. Duodenal-jejunal endoluminal liner
6. Surgery of any kind within 3 months prior to Day 0 (Baseline) with the exception of minor procedures or determined by the Investigator to be clinically relevant for participation in the study, or any planned surgery during the study.
7. Renal impairment as estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2, calculated at screening using the recommended method for estimating eGFR in adults from the National Kidney Foundation Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2021) equation (Charles 2024).
8. Acute kidney injury or dialysis within the last 3 months prior to the screening visit
9. Current malignancy with the exception of participants with basal cell carcinoma of this skin, suqamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy.
10. Positive results at screening that indicate an active virological infection at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus.
11. Previous organ or bone marrow transplant.
12. History and/or confirmed seizure disorder; reports febrile and/or idiopathic seizures occurring within the past 2 years.
13. Unstable cardiovascular disease as determined by the Investigator or medical history of myocardial infarction or arterial thromboembolic events within 3 months prior to screening or severe or unstable angina, NYHA Class III or IV disease, or a 12-lead ECG showing QTc interval (Fridericia's formula) \>450 msec (males) or \>470 msec (females), any tachyarrhythmia, pathologic Q waves, or any other abnormality deemed clinically significant in the opinion of the investigator.
14. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participants' participation for the full duration of the study, or is not in the best interest of the participants to participate in the opinion of the Investigator.
15. Have history of any of the following:

    1. Major Depressive Disorder (MDD)
    2. A lifetime history of suicide attempts
    3. Other severe psychiatric disorder(s) (e.g., schizophrenia, bipolar disorder, etc.)
    4. Use of anti-depressant medication
16. Have a Patient Health Questionnaire-9 (PHQ-9) score ≥ 10 at screening and/or Day 0 (Baseline).
17. At screening or Day 0 (Baseline) have any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) or any suicidal behavior in the lifetime or previous month.
18. History or presence of drug abuse (including medicinal and recreational marijuana use) within the 1 year prior to Day 0 (Baseline) or urine drug assay at screening or Day 0 (Baseline) positive (includes: amphetamines, barbiturates, cocaine metabolites, opiates, benzodiazepines, and cannabinoids).
19. Prior exposure to study drugs

    1. Nimacimab injection
    2. Glucagon-like peptide-1 (GLP-1) agonist.
    3. Allergy to active or inactive component of Nimacimab
    4. Allergy to active or inactive component(s) of GLP-1 agonist
20. Female participants who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study.
21. Aspartate aminotransferase (AST) or alanine transaminase (ALT) \> 3 × upper limit of normal (ULN) at screening. One repeat test may be allowed within 7 days of the receiving the result, at the discretion of the Investigator.
22. Absolute neutrophil count ≤ 1.5 × 109/L.
23. Platelets ≤ 120 × 109/L.
24. Hemoglobin (Hgb) \< 13.5 g/dL in males and \< 12 g/dL in females.
25. Currently or have participated in a study of an investigational product or used an investigational device within 12 weeks and/or 5 times the half-life of the investigational product prior to the (Day 0, Baseline) first dose of study treatment.
26. Current use of any medication that is known to cause weight loss or participation in a structured weight loss program within the last 6 months prior to screening
27. Employees of the Sponsor, contract research organization (CO) involved in the conduct of the study, or investigational site, or immediate family members of the employees.
28. History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 5 ounces \[150 mL\] of wine or 12 ounces \[360 mL\] of beer of 1.5 ounces \[45 mL\] of hard liquor) within 6 months of screening.

Primary outcomes:
measure: Percent change in body weight
timeFrame: From Baseline to Week 26
Secondary outcomes:
measure: Change in body weight
timeFrame: From Baseline to Week 26
measure: Change in waist circumference
timeFrame: From Baseline to Week 26
measure: Change in lean versus fat mass ratio measured by DXA
timeFrame: From Baseline to Week 26
measure: Change in BMI
timeFrame: From Baseline to Week 26
measure: Percent of participants with greater than/equal to 5% body weight reduction as well as greater than/equal to 10% body weight reduction
timeFrame: From Baseline to Week 26
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group
state: Alabama
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc.
state: California
city: Waterbury
country: United States
facility: Chase Medical Research, LLC
state: Connecticut
city: Atlanta
country: United States
facility: ACCEL Research Sites
state: Georgia
city: Gainesville
country: United States
facility: Center for Advanced Research & Education
state: Georgia
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: Lincoln
country: United States
facility: Be Well Clinical Studies
state: Nebraska
city: Las Vegas
country: United States
facility: Palm Research Center
state: Nevada
city: Portsmouth
country: United States
facility: ActivMed Practices & Research
state: New Hampshire
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Wilmington
country: United States
facility: Accellacare of Wilmington
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research, LLC
state: North Dakota
city: Dallas
country: United States
facility: Velocity Clinical Research, Dallas
state: Texas
city: Round Rock
country: United States
facility: Be Well Clinical Studies
state: Texas
city: Charlottesville
country: United States
facility: Charlottesville Medical Research
state: Virginia
city: Renton
country: United States
facility: Rainier Clinical Research Center
state: Washington
Study officials:
affiliation: Skye Bioscience, Inc.
name: Chief Development Officer
role: STUDY_DIRECTOR
References: