Study to Evaluate the Effect on Obesity of QW Nimacimab and QW Nimacimab Co-administered With Semaglutide vs Placebo (CBeyond)

A Phase 2 Study of QW Nimacimab Injection, Compared to Placebo Injection and QW Weekly Nimacimab Injection Co-administered With Semaglutide in Participants Who Are Overweight or Obese

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

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity
• Intervention / Treatment: Biological: Nimacimab injection; Biological: Nimacimab placebo injection; Combination product: semaglutide injection; Biological: Nimacimab 300 mg injection

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. A study extension has been added to include additional 26 weeks of treatment and 13 weeks of follow up for qualifying participants starting May2025.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group
  • California
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Accel Research Sites
    • Gainesville, Georgia, United States, 30501
      • Center for Advanced Research & Education
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Be Well Clinical Studies
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Research Center
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • ActivMed Practices & Research
  • New York
    • New York, New York, United States, 11375
      • Weill Cornell Medicine
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Accellacare of Wilmington
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research, LLC
  • Texas
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Research, Dallas
    • Round Rock, Texas, United States, 78681
      • Be Well Clinical Studies
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Extension Eligibility Criteria

Participants are eligible to be included in the extension only if all the following criteria apply:

1. Completed Week 26 of the Main study including Week 25 on study treatment. Participants who completed Week 26 of the Main study but discontinued study treatment prior to that visit are not eligible to participate.

   1. Participants in the combination arms (Nimacimab Injection or placebo + Semaglutide) of the Main study must roll over within 4 weeks of Main study Week 26
   2. Participants in the monotherapy arms (Nimacimab Injection or placebo) of the Main study can roll over anytime after they have completed Week 26 on study treatment but before completing the 13-week follow-up period.
2. Does not have any condition that interferes with the ability to complete the Extension in the judgment of the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nimacimab injection; Nimacimab injection 200 mg	Biological: Nimacimab injection; Nimacimab injection 200 mg
Placebo Comparator: Nimacimab placebo injection; Matching nimacimab placebo injection	Biological: Nimacimab placebo injection; matching nimacimab placebo injection
Experimental: Semaglutide injection + Nimacimab injection 200 mg; Semaglutide injection administered according to dose escalation described in semaglutide prescribing information plus concomitant administration of Nimacimab Injection 200 mg	Biological: Nimacimab injection; Nimacimab injection 200 mg; Combination product: semaglutide injection; semaglutide injection 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg + nimacimab 200 mg
Active Comparator: Semaglutide injection + Nimacimab placebo injection; Semaglutide injection administered according to dose escalation described in semaglutide Prescribing Information plus concomitant administration of Nimacimab Injection or matching placebo injection	Biological: Nimacimab placebo injection; matching nimacimab placebo injection; Combination product: semaglutide injection; semaglutide injection 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg + nimacimab 200 mg
Experimental: Open-label 300 mg Nimacimab injection (study extension); Weekly nimacimab injection 300 mg open-label (study extension)	Biological: Nimacimab 300 mg injection; Nimacimab injection 300 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in body weight (main study)	Percent of participants who have a reduction in body weight	From Baseline to Week 26
Nature, frequency and severity of AEs (study extension)	Nature, frequency and severity of treatment-emergent adverse events, including serious adverse events and adverse events of special interest	Baseline through Week 38 of study extension (approximately 10 months of participation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body weight (main study)	Change in body weight in kg	From Baseline to Week 26
Change in waist circumference (main study)	Change in waist circumference in cm	From Baseline to Week 26
Change in waist circumference (study extension)	Change in waist circumference in cm	From baseline to Week 26 of study extension (approximately 7 months of participation)
Change in lean versus fat mass ratio measured by DXA (main study)	Change in lean versus fat mass ratio measured by DEXA (DXA) scan.	From Baseline to Week 26
Change in lean versus fat mass ratio measured by DXA (study extension)	Change in lean versus fat mass ratio measured by DEXA (DXA) scan.	From baseline to Week 26 of study extension (approximately 7 months of participation)
Change in BMI (main study)	Change in BMI (weight and height will be combined to report BMI in kg/m^2)	From Baseline to Week 26
Change in BMI (study extension)	Change in BMI (weight and height will be combined to report BMI in kg/m^2)	From baseline to Week 26 of study extension (approximately 7 months of participation)
Percent of participants with greater than/equal to 5% body weight reduction as well as greater than/equal to 10% body weight reduction (main study)	Percent of participants with specific body weight reduction (percent based on weight measured in kg)	From Baseline to Week 26
Percent change in body weight (kg) (study extension)	Change in body weight (percent based on weight measured in kg)	From baseline to Week 26 of study extension (approximately 7 months of participation)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in lean versus fat mass ratio	Change in lean versus fat mass ratio measured by DEXA (DXA) scan.	Baseline to Week 26 and Week 38
Sleep stage quantification	Effect of Nimacimab injection 200 mg once weekly compared to placebo injection utilizing the Dreem 3S 5-channel dry-electrode headband in a sub-set of participants, to measure brain waves at each 30-sec epoch and process raw EEG data and accelerometer data to provide automatic sleep staging according to the AASM classification	Screening, week 12, week 24, and week 34

Collaborators and Investigators

• Sponsor: Skye Bioscience, Inc.
• Collaborators: Bird Rock Bio Sub, Inc.
• Investigators: Study Director: Chief Development Officer, Skye Bioscience, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2024
• Primary Completion (Estimated): November 20, 2026
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: August 19, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 29, 2024

Study Record Updates

• Last Update Posted (Estimated): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Nimacimab
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Therapeutics; Drug Administration Routes; Drug Therapy; Injections; semaglutide
• Other Study ID Numbers: SBI-018-201

Drug and device information, study documents

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