Detailed Description
This is a phase 2, double-blind, placebo-controlled study. Following screening, at their baseline visit, participants will initiate treatment with semaglutide at 0.25 mg/week and follow the product labelled dose escalation schedule until reaching the dose of 1.0 mg/week. Participants will remain on this dose until the end of study (EOS) visit.
At the baseline visit, participants will be randomized in a 1:1:1 ratio to receive AT673 25 mg, or 50 mg, or matching placebo, respectively, once weekly at the same time as semaglutide.
Participants will receive AT673 / placebo injections concurrently with Semaglutide during weekly clinic visits. Treatment with the AT673 / placebo will continue through the end of 13 weeks. This will be followed by a 4-week safety follow-up. The end of study visit will be at week 17.
Eligibility Criteria
Age Range: 18 years to No maximum
Inclusion Criteria:
1. Signed informed consent prior to start the Screening Visit procedures.
2. Female and male participants ≥18 years of age at time of consent
3. BMI g ≥27.0 kg/m2 at screening.
4. HbA1c ≥7 and ≤10% (53-86 mmol/mol) at screening.
5. Diagnosis of type 2 diabetes mellitus for ≥ 180 days prior to screening.
6. Either treated with diet and exercise alone or on stable (at least 90 days prior to screening) treatment with metformin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, sulfonylurea, and/or DPP4 inhibitor as monotherapy or combination therapy, per approved local label.
a) Note: Participants treated with sulfonylureas and/or DPP4 inhibitors must discontinue these at least 24 hours prior to initiation of semaglutide.
7. Participant has had at least 1 unsuccessful attempt at weight loss by diet and exercise in the opinion of the investigator.
8. Women of childbearing potential (WOCBP) meeting the criteria below:
i) Non-lactating and has a negative pregnancy test at screening and baseline -AND- ii) Uses an acceptable method of contraception as determined by the Investigator or Sub-Investigator for the duration of the study and 30 days following the last dose of study drug
9. Participants must, in the opinion of the Investigator, be suitable candidates to receive semaglutide (Wegovy®) as indicated according to the product label.
Exclusion Criteria:
1. Participant has had gastric bypass or other bariatric surgery or endoscopic procedure or any metabolic procedures (e.g. duodenal resurfacing, intragastric balloon, etc.) except for the following:
1. Liposuction and/or abdominoplasty that was performed \> 1 year before screening
2. Laparoscopic gastric band that was removed \> 1 year before screening
3. Intragastric balloon that was removed \> 1 year before screening
4. Duodenal-jejunal bypass sleeve that was removed \> 1 year before screening.
2. Participant has had a self-reported or medically recorded change in body weight \> 5% within 3 months of screening OR has recorded change in body weight \>3% between screening and randomization.
3. Participant is currently using insulin or used insulin within 3 months before screening.
4. Participant is currently using sulfonylureas and/or DPP4 inhibitors and is unable or unwilling to discontinue the use of these medications at least 24 hours prior to initiation of semaglutide.
5. Participant has a form of diabetes other than type 2.
a. Note: Previous diagnosis of gestational diabetes is permitted so long as the participant meets all inclusion and none of the exclusion criteria.
6. Participant is currently using or used within 3 months before screening any weight reducing medication including pramlintide, sibutramine, orlistat, zonisamide, topiramate, phentermine, naltrexone, bupropion.
7. Participant is currently using or used within 6 months before screening any medication that contains a GLP-1R agonist component or a GIPR modulator (either by prescription or as part of a clinical study)
8. For participants with a history of prior GLP-1R agonist use (\> 6 months prior to screening):
1. Participant has had a previous intolerance or hypersensitivity to GLP-1 receptor agonists or any of its excipients.
2. Participant has previously discontinued a GLP-1 receptor agonist after continuous treatment for 6 months or longer due to not meeting personal weight loss goals.
9. Participant is taking any medication that, may cause weight gain unless the participant has used these medications for more than 6 months at a stable dose prior to screening.
10. Participant has hepatic liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase levels \>2.5, or total bilirubin levels \> 1.5 times the upper limit of normal (ULN) at screening.
11. Participant's current alcohol intake exceeds 14 units/week for men or 7 units/week for women (1 unit = half pint of beer, 1 glass of wine, 1 measure of spirits).
12. Participant has a recent history of illicit substance use (\< 3 months) or in the opinion of the Investigator suspicion of current illicit substance use.
13. Participant has uncontrolled hypertension at screening (SBP above or equal to 160 mmHg and/or diastolic blood pressure above or equal to 100 mmHg).
14. A corrected QT interval (QTc) of \> 450 msec in males or \> 470 msec in females at screening, or history of long QT syndrome.
15. Concurrent participation in another interventional study (e.g., of a drug, over the counter product, device) or within ≤90 days or 5 half-lives prior to Screening.
16. Participant is unable to understand and communicate with the investigators; or to understand the protocol requirements, instructions, study-related restrictions, nature, scope, and possible consequences of the clinical study; or is unlikely to comply with the study requirements (e.g., uncooperative attitude and improbability of completing the clinical study).
17. Participant is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff, or relative thereof directly involved in the conduct of the study, or employee of the sponsor, site, or Contract Research Organization (CRO).
18. Participant whose obesity can be traced to a medical cause, suggestive of genetic or syndromic obesity of an endocrinologic disorder (e.g., hypothyroidism, Cushings syndrome, Prader-Willi syndrome).
19. Participant has a history of an active or untreated malignancy or in remission from a clinically significant malignancy for less than 5 years, except for basal cell carcinoma.
20. Participant has a glomerular filtration rate \< 60 mL/min/1.73 m2.
21. Participant has a history of major psychiatric disorders within 5 years or lifetime history of suicide attempt.
22. Participant has any suicidal ideation of type 4 or 5 on the C-SSRS at screening.
23. Participant with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia (MEN) syndrome type 2.
24. Participant with a previous history of chronic pancreatitis, or acute pancreatitis within 6 months prior to screening.
25. In the opinion of the Investigator, any disorder, condition, inability or unwillingness not covered by the exclusion criteria that may interfere with study procedures, assessments or participant's safety.