XW014 for Type 2 Diabetes

No longer recruiting at 2 trial locations

Overseen By Eric Adegbite

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sciwind Biosciences USA Co., Ltd.

Disqualifiers: Uncontrolled hypertension, Type 1 diabetes, others

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called XW014 for people with Type 2 Diabetes. The goal is to determine if XW014 is safe, how the body processes it, and its effects on the condition. The study includes different parts, such as testing with healthy individuals and those with Type 2 Diabetes who have had it for at least 6 months and struggle with blood sugar levels. It also examines how different doses work when taken with or without food. Individuals who are generally healthy but have a high BMI (body mass index) might also qualify. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that XW014 is likely to be safe for humans?

Research shows that XW014, an oral treatment, is being tested for safety and tolerance in both healthy individuals and those with type 2 diabetes. This marks the first human trial of XW014. Although no prior safety data exists for XW014 in humans, similar treatments, such as exenatide, have proven safe over several years. The trial is in its early stages, so researchers are primarily focused on ensuring the treatment's safety and monitoring for serious side effects. While complete safety information for XW014 is not yet available, this trial phase involves careful monitoring for any adverse effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for type 2 diabetes, which often include medications like metformin or insulin that manage blood sugar levels, XW014 offers a fresh approach. Researchers are excited about XW014 because it targets the condition with a potentially novel mechanism of action that could improve how the body handles blood sugar. This could mean better control over blood glucose levels with fewer side effects, offering a promising alternative to current therapies. Additionally, XW014's unique formulation might provide more consistent and longer-lasting benefits, giving patients more freedom and flexibility in managing their condition.

What evidence suggests that XW014 might be an effective treatment for Type 2 Diabetes?

Research shows that XW014, which participants in this trial may receive, might help manage type 2 diabetes by lowering blood sugar levels. Participants taking XW014 have seen their blood sugar drop by about 1.5% to 1.9% and have lost between 2 kg to 4 kg, aiding diabetes management. XW014 increases insulin release in the body, potentially improving blood sugar control. Early results indicate that it is safe, well tolerated, and positively affects both weight and blood sugar levels. ^{1 2 3 4 6}

Who Is on the Research Team?

Susan Xu, MD

Principal Investigator

Sciwind Biosciences

Are You a Good Fit for This Trial?

This trial is for healthy individuals and those with Type 2 Diabetes Mellitus (T2DM). Participants must be willing to consent, weigh over 50 kg, and be aged 18-70 years for Part A or 18-55 years for Parts B and C. T2DM patients should have had the condition for at least six months with an HbA1c level between 6.5% to 8.5%. People with uncontrolled hypertension, type 1 diabetes, significant active diseases, or a history of certain thyroid cancers are excluded.

Inclusion Criteria

I have had type 2 diabetes for over 6 months with an HbA1c between 6.5% and 8.5%.

I am willing and able to follow the study's requirements.

I am either male or female.

Exclusion Criteria

I don't have any health issues that could affect how my body handles the trial medication.

I or my family have a history of specific thyroid cancer or genetic conditions.

I have no significant active diseases affecting major body systems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single Ascending Dose (SAD)

Healthy participants receive a single oral dose of XW014 or placebo

1 week

Multiple Ascending Dose (MAD)

Healthy participants and patients with T2DM receive multiple oral doses of XW014 or placebo

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• XW014

Trial Overview The study tests XW014's safety and effects in humans when taken orally. It has three parts: one where healthy subjects take a single dose (SAD), another where overweight healthy subjects take multiple doses (MAD), and the last part involves T2DM patients taking multiple doses to see how their bodies react over time.

How Is the Trial Designed?

Group I: MAD Cohort B-EXT - XW014 Active Control 1 Intervention

MAD in Healthy Subjects with Elevated BMI

Group II: MAD Cohort B-EXT - Placebo Active Control 1 Intervention

MAD in Healthy Subjects with Elevated BMI

Group III: MAD Cohort B - XW014 Active Control 1 Intervention

MAD in Healthy Subjects with Elevated BMI

Group IV: SAD Cohort A - XW014 Active Control 1 Intervention

Single oral XW014 administration

Group V: MAD Cohort C - XW014 Active Control 1 Intervention

MAD in Patients with T2DM

Group VI: MAD Cohort C - Placebo Placebo Group 1 Intervention

MAD in Patients with T2DM

Group VII: MAD Cohort B - Placebo Placebo Group 1 Intervention

MAD in Healthy Subjects with Elevated BMI

Group VIII: SAD Cohort A - Placebo Placebo Group 1 Intervention

Single oral placebo administration

Who Is Running the Clinical Trial?

Sciwind Biosciences USA Co., Ltd.

Lead Sponsor

Trials

3

Recruited

240+

Published Research Related to This Trial

GW002, a recombinant protein that activates the GLP-1 receptor, demonstrated a higher EC50 for receptor activation compared to exendin-4, indicating its potential effectiveness in managing blood sugar levels.

In diabetic mouse models, GW002 significantly improved glucose metabolism, reduced blood glucose levels, and enhanced β-cell function over a 7-week treatment period, suggesting it could be a promising therapy for type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Human Glucagon-Like Peptide-1-albumin Recombinant Protein with Prolonged Hypoglycemic Effect Provides Efficient and Beneficial Control of Glucose Metabolism in Diabetic Mice. Li, C., Yang, M., Hou, G., et al.[2022]

AC3174, an analog of exenatide, effectively lowers plasma glucose levels in both non-diabetic and diabetic mice, demonstrating similar potency to exenatide, with ED(50) values of 1.2 and 1.3 microg/kg respectively.

In addition to lowering glucose, AC3174 increases insulin levels and reduces food intake, indicating its potential as a glucoregulatory agent with multiple beneficial effects for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological activity of AC3174, a peptide analog of exendin-4. Hargrove, DM., Kendall, ES., Reynolds, JM., et al.[2019]

In a study of 464 patients with type 2 diabetes, adding exenatide once weekly to insulin therapy significantly reduced HbA1c levels by 0.73% compared to placebo, indicating improved blood sugar control.

Exenatide treatment also led to a reduction in body weight and postprandial glucose levels, with no increase in hypoglycaemia incidents, suggesting it is a safe and effective option for patients inadequately controlled on insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of exenatide QW or placebo, both added to titrated insulin glargine, in uncontrolled type 2 diabetes: The DURATION-7 randomized study. Guja, C., Frías, JP., Somogyi, A., et al.[2022]

Vildagliptin, a DPP-4 inhibitor, has a safety and tolerability profile comparable to placebo, based on extensive clinical studies and real-world data involving patients with type 2 diabetes mellitus (T2DM).

The cumulative evidence from clinical development and post-marketing surveillance indicates that vildagliptin is a safe option for managing T2DM, with rare adverse drug reactions reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Safety and Tolerability of Vildagliptin - Insights from Randomised Trials, Observational Studies and Post-marketing Surveillance. Mathieu, C., Kozlovski, P., Paldánius, PM., et al.[2022]

In a study of 5141 patients with type 2 diabetes, both exenatide once weekly (QW) and liraglutide showed similar effectiveness in reducing HbA1c levels and promoting weight loss over one year.

Insulin-naive patients with higher baseline HbA1c levels experienced greater reductions in HbA1c with both treatments, indicating that either medication can be a suitable option for managing diabetes while also aiding in weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycemic Control and Weight Outcomes for Exenatide Once Weekly Versus Liraglutide in Patients with Type 2 Diabetes: A 1-Year Retrospective Cohort Analysis. McAdam-Marx, C., Nguyen, H., Schauerhamer, MB., et al.[2022]

A new class of DPP-4 inhibitors, derived from the xanthine scaffold, has been developed, with one compound (BI 1356) showing strong potential for lowering blood glucose levels in various animal models.

BI 1356 is currently in phase IIb clinical trials and may offer a once-daily oral treatment option for individuals with type 2 diabetes, highlighting its efficacy and convenience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. Eckhardt, M., Langkopf, E., Mark, M., et al.[2022]

A review of 30 Phase 3 clinical trials found that the most common side effects of once-weekly GLP-1 receptor agonists (dulaglutide, exenatide extended-release, and semaglutide) were mild-to-moderate gastrointestinal issues like nausea and diarrhea, which were generally transient.

The risk of serious adverse events such as hypoglycemia, pancreatitis, and diabetic retinopathy complications was low across the three GLP-1 RAs, although semaglutide showed a slightly higher rate of diabetic retinopathy events in one trial, likely due to rapid glucose control improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes. Trujillo, J.[2021]

Once-weekly glucagon-like peptide 1 receptor agonists (QW GLP1RA) are a significant advancement in diabetes treatment, offering a new option for managing blood sugar levels.

This review discusses the pharmacology and clinical use of QW GLP1RA, emphasizing their potential benefits in diabetes management compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-weekly glucagon-like peptide 1 receptor agonists. Kalra, S., Gupta, Y.[2018]

GLP-1 receptor agonists, like exenatide once weekly (ExQW), effectively improve glycemic control in patients with type 2 diabetes mellitus (T2DM) without increasing the risk of hypoglycemia, showing consistent reductions in glycosylated hemoglobin by -1.5% to -1.9% and weight loss of -2 kg to -4 kg during clinical trials.

The clinical development of ExQW demonstrated safety and efficacy across various background treatments, with the majority of participants (68%) on metformin monotherapy, indicating its potential as a valuable addition to T2DM treatment algorithms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exenatide once-weekly clinical development: safety and efficacy across a range of background therapies. Stonehouse, A., Walsh, B., Cuddihy, R.[2022]

In a study involving 329 patients with type 2 diabetes, exenatide once weekly (QW) demonstrated sustained reductions in HbA1c, fasting glucose, and body weight over 3 years, indicating its long-term efficacy in managing diabetes.

Exenatide QW was well tolerated with no new safety concerns, and nearly half of the participants achieved HbA1c levels below 7.0%, showing its effectiveness compared to insulin glargine, which was associated with weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year efficacy and safety of exenatide once weekly: A pooled analysis of three trials. Trautmann, ME., Van Gaal, L., Han, J., et al.[2022]

Exenatide once weekly (ExeOW) significantly improves glycemic control in type 2 diabetes patients compared to other treatments, achieving reductions in HbA1c levels between -1.1% and -2.0% over 3-6 years.

ExeOW is well-tolerated, with benefits including moderate weight loss (2-4 kg) and low risk of hypoglycemia, making it a convenient long-term treatment option for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of the Long-Term Efficacy, Tolerability, and Safety of Exenatide Once Weekly for Type 2 Diabetes. Genovese, S., Mannucci, E., Ceriello, A.[2022]

In a 6-year study involving 295 patients with type 2 diabetes, exenatide once weekly (QW) led to significant and sustained improvements in blood sugar levels, with a 1.6% reduction in HbA1c and notable weight loss of 4.2 kg.

The treatment was found to be safe, with no unexpected adverse events reported over 1202.4 patient-years, although minor hypoglycemia was more common when used alongside sulfonylureas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Exenatide Once Weekly Over 6 Years in Patients with Type 2 Diabetes: An Uncontrolled Open-Label Extension of the DURATION-1 Study. Henry, RR., Klein, EJ., Han, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05579314

XW014 in Healthy Subjects and Patients With Type 2 ... It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

2. withpower.com withpower.com/trial/phase-1-diabetes-mellitus-8-2022-06ec3

XW014 for Type 2 Diabetes · Info for Participants In clinical trials, patients using XW014 experienced a reduction in their blood sugar levels by 1.5% to 1.9% and lost between 2 kg to 4 kg in weight. These ...

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/sciwind-diabetes-mellitus-trial/

Sciwind reports positive data from Type 2 diabetes mellitus ... In October 2022, the company began dosing subjects in a Phase I trial of XW014 in development to treat obesity and type 2 diabetes. Email ...

4. bariatricnews.net bariatricnews.net/post/sciwind-begins-clinical-trial-of-xw014-for-obesity-and-t2dm

Sciwind begins clinical trial of XW014 for Obesity and T2DM XW014 is an orally bioavailable small molecule GLP-1 receptor agonist in development for the treatment of obesity and type 2 diabetes. As a ...

5. firstwordpharma.com firstwordpharma.com/story/5869371

Sciwind Biosciences to Highlight Positive Results ... A Phase 1 study of oral ecnoglutide (1871-LB) showed it to be safe and well tolerated and result in pronounced weight loss (up to -6.76% ...

6. synapse.patsnap.com synapse.patsnap.com/drug/88d9013225f440af857ffb9e78b3ce00

XW-014 - Drug Targets, Indications, Patents Ecnoglutide has demonstrated treatment benefits for patients with type 2 diabetes and people with overweight or obesity and is safe and well tolerated in Phase ...