MBL949 for Obesity

No longer recruiting at 4 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must be taking: Metformin, SGLT2i, DDP4, Acarbose

Disqualifiers: Bariatric surgery, Myocardial infarction, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 14 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new treatment called MBL949, an experimental therapy for individuals struggling with obesity, regardless of Type 2 Diabetes status. Participants will receive varying doses of MBL949 or a placebo to evaluate the treatment's effectiveness. It suits those with a body mass index (BMI) of 32 or higher, who have maintained a stable weight recently, and may be managing Type 2 Diabetes with medications like Metformin. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

If you are taking medications for Type 2 Diabetes, you can continue with Metformin, SGLT2 inhibitors, DDP4 inhibitors, or Acarbose, as long as they have been stable for 90 days before joining the trial. The protocol does not specify about other medications, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that MBL949 is safe and generally well-tolerated in people. Some participants experienced mild side effects, mostly related to the stomach, such as nausea or an upset stomach. For most, these side effects were not severe and resembled those seen with other obesity treatments.

MBL949 has also undergone testing in animals like mice, rats, dogs, and monkeys. These studies found it to be safe and effective in reducing food intake and body weight.

Overall, while some side effects have been reported, research suggests that MBL949 is safe for use in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about MBL949 because it offers a new approach to treating obesity, with or without type 2 diabetes. Unlike standard treatments like bariatric surgery or medications such as metformin and GLP-1 receptor agonists, MBL949 is administered subcutaneously and explores different dosing regimens, potentially enhancing its effectiveness and tolerability. Additionally, MBL949's novel dosing strategies, involving varied dosages over the treatment period, aim to optimize weight loss while minimizing side effects, marking it as a promising alternative in obesity management.

What evidence suggests that this trial's treatments could be effective for obesity and Type 2 Diabetes Mellitus?

Research has shown that MBL949, a drug targeting a specific receptor, reduced food intake and body weight in animal studies with mice, rats, dogs, and monkeys. However, in human studies, weight loss was minimal after taking the drug every two weeks for 14 weeks. The treatment was generally safe and well-tolerated, but the weight loss effects were not significant, especially given the number of reported side effects. This suggests that while MBL949 appears promising in animal studies, it has not been as effective in humans. Participants in this trial will be assigned to different arms receiving varying dosages of MBL949 or a placebo to further evaluate its effectiveness and safety in humans. ^{1 2 3 5 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Inclusion Criteria

Body mass index: ≥ 32 kg/m2, weight ≥ 77 kg, stable body weight i.e., less than 1.5 kg self-reported change within 90 days

Diagnosed T2DM as documented by medical history and confirmed by Investigator and with diagnosed duration < 10 yrs, HbA1c ≤ 9%, and fasting C-peptide ≥ 0.2 ng/ml

If treated for T2DM, treatment must be limited to diet and exercise and treatment with one of the following anti-diabetic agents (stable for 90 days prior to randomization): Metformin, SGLT2i inhibitors (if prescribed as the first line, ie. single agent), DDP4 inhibitors, Acarbose

Exclusion Criteria

History of bariatric surgery, Roux-en-Y Gastric Bypass, Sleeve Gastrectomy, gastric banding, and any other intrabdominal procedures designed for weight loss at screening

Participation in organized weight reduction program within 6 months of screening

Vitals at screening: systolic blood pressure less than 95 mm Hg or greater than 155 mm Hg, diastolic blood pressure less than 60 mg Hg or greater than 95 mm Hg, pulse rate less than 56 or greater than 110 bpm

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

5 weeks

Treatment

Participants receive MBL949 or placebo over 14 weeks with 8 biweekly doses

14 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MBL949

How Is the Trial Designed?

Group I: MBL949 Arm 4 Active Control 1 Intervention

MBL949 one 1.5 mg dose followed by seven doses of 2.2 mg

Group II: MBL949 Arm 1 Active Control 1 Intervention

MBL949 one 3 mg dose followed by two doses of 6 mg followed by five doses of 4.5 mg

Group III: MBL949 Arm 5 Active Control 1 Intervention

MBL949 one 3 mg dose followed by two doses of 6 mg followed by five doses of 7.5 mg

Group IV: MBL949 Arm 2 Active Control 1 Intervention

MBL949 two 3 mg doses followed by six doses of 4.5 mg

Group V: MBL949 Arm 3 Active Control 1 Intervention

MBL949 one 12 mg dose followed by seven doses of 4.5 mg

Group VI: Placebo Placebo Group 1 Intervention

Placebo to MBL949

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39148430/

A Growth Differentiation Factor 15 Receptor Agonist in ... MBL949 was generally safe and effective with reduced food intake and body weight in mice, rats, dogs, and monkeys.

2. oak.novartis.com oak.novartis.com/53811/

MBL949, a long acting GDF15 receptor agonist, in ... In the Phase 2 trial, weight loss was minimal following biweekly dosing of MBL949 for 14 weeks. MBL949 was safe and generally tolerated in ...

3. novctrd.com novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2083

Thank you! The trial sponsor reviewed the data and decided MBL949 did not have enough of an effect on weight loss given the number of adverse events. Because of this, the ...

4. academic.oup.com academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgae550/7734046

A Growth Differentiation Factor 15 Receptor Agonist in ... In the phase 2, weight loss was minimal following biweekly dosing of MBL949 for 14 weeks. MBL949 was safe and generally tolerated in humans over ...

5. trial.medpath.com trial.medpath.com/clinical-trial/ea5e296847136a73/nct05199090-randomized-placebo-controlled-study-mbl949-obesity-diabetes

Study to Assess Safety, Tolerability and Efficacy of SC ... The study comprised a screening/baseline period of up to 35 days (5 weeks), a 14-week treatment period in which participants were administered MBL949 or ...

6. synapse.patsnap.com synapse.patsnap.com/drug/062025e22c9b4c5aa5d393d2d007b2f4

MBL-949 - Drug Targets, Indications, Patents MBL949 was safe and generally tolerated in humans over the dose range tested, adverse events of the gastrointestinal system were the most frequent observed.