A Phase IIb, Multicenter, Open-Label, Prospective Study of Bremelanotide in Diabetic Kidney Disease

NCT05709444 | Completed Phase 2 FDA Drug

• 1 other identifier: BMT-701
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 9

Brief Summary

This is a prospective, open-label trial to assess the efficacy of melanocortin receptor agonist bremelanotide (BMT) when administered with RAAS inhibition therapy after six months in subjects with Type II diabetic nephropathy. After six months of therapy, all subjects will remain in trial for further assessment and undergo a diagnostic renal biopsy to assess the effect of melanocortin therapy on diabetic histopathology at 12 months.

Conditions

Kidney Disease

Outcome Measures

Primary Outcomes (2)

• To demonstrate the efficacy of 0.5 mg subcutaneous BMT (given twice a day), used in combination with a subject's maximum tolerated dose of RAAS inhibition therapy, reduces urinary protein by 50% from baseline UP/Cr levels.

  Proportion of subjects with Type II diabetic nephropathy who achieve a 50% reduction in their urine protein Cr (UP/Cr) ratio after six months of combined therapy (RAAS inhibition therapy plus BMT). Inhibition therapy to reduce urinary protein and maintain podocyte density and functions in subjects with Type II diabetic nephropathy after six months.

  Baseline to after six months of combined therapy (RAAS inhibition therapy plus BMT).

• To determine the incidence of overall adverse events, related adverse events, a composite of adverse events of special interest, serious adverse events, and the incidence of BMT discontinuation.

  Proportion of subjects with Type II diabetic nephropathy who achieve a 50% reduction in their urine protein Cr (UP/Cr) ratio after six months of combined therapy (RAAS inhibition therapy plus BMT) to determine the incidence of adverse events, related adverse events, adverse events of special interest, serious adverse events and BMT discontinuation.

  Baseline to after six months of combined therapy (RAAS inhibition therapy plus BMT).

Secondary Outcomes (4)

• To evaluate the percentage of patients receiving SQ BMT in combination with RAAS inhibition to achieve a complete remission defined as a UP/Cr ratio of ≤ 500 mg/gm at 6 months.

  < 500 mg/gm at 6 months.

• To evaluate the percentage of patients receiving SQ BMT in combination with RAAS inhibition to achieve partial remission defined as a UP/Cr ratio of ≥ 50% reduction from baseline UP/Cr at 6 months.

  ≥ 50% reduction from baseline UP/Cr at 6 months.

• To determine the percentage of patients to achieve a clinical response defined as ≥ 30% reduction from BL UP/Cr at 6 months.

  ≥ 30% reduction from BL UP/Cr at 6 months.

• To measure the percentage of subjects receiving SQ BMT in combination with RAAS inhibition therapy whose eGFR decreases by less than 5.0 mL/min/1.73m2 from baseline at 6 months.

  <5.0mL/min/1.73m^2 from baseline at 6 months.

Study Arms (1)

Subcutaneous Bremelanotide

EXPERIMENTAL

BMT sterile aqueous solution for injection provided as a prefilled syringe, administered by subcutaneous (SQ) injection into the abdomen.

Drug: Bremelanotide; Drug: RAAS inhibition therapy

Interventions

Bremelanotide DRUG

Bremelanotide is a cyclic, heptapeptide analog of the endogenous peptide alpha melanocortin stimulating hormone (αMSH).

Also known as: Bremelanotide acetate

Subcutaneous Bremelanotide

RAAS inhibition therapy DRUG

RAS-acting agents are medicines acting on a hormone system that helps to control blood pressure and the amount of fluid in the body.

Also known as: Angiotensin-converting enzyme (ACE) inhibitors, Angiotensin II receptor blockers (ARBs)

Subcutaneous Bremelanotide

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged between 18 years and 80 years, inclusive, willing, and able to understand the risks of the trial and consents to trial conduct documented by the signing of the trial informed consent form.
• Have a diagnosis of Type II diabetes mellitus in a controlled state (defined as Hemoglobin A1c (HgbA1c) ≤ 10%). Note: Efforts will be made to enroll subjects with known diabetic retinopathy and diabetic peripheral neuropathy to examine the potential benefits of melanocortin receptor activation outside kidney disorders.
• Have a BMI ≤ 45 kg/m\^2 at screening.
• Have a diagnosis of Stage I, II, or III diabetic nephropathy, confirmed by renal biopsy within 5 years of Screening.
• Have been on a stable dose of oral diabetic agents or insulin injections for ≥3 months prior to enrollment. Sliding scale dose of insulin based on blood sugar readings is acceptable as long as the type of insulin has remained stable.
• Be on a stable, maximum tolerated dose (as determined by the Investigator) of an angiotensin-converting enzyme (ACE) or angiotensin-receptor blockers (ARB) as primary antihypertensive therapy (blood pressure of \<140/90 at screening).
• Note: If the blood pressure is \>140/90 at screening it can be repeated twice and if it is \<140/90 upon repeat the subject is eligible for study enrollment.
• Note: The addition or dose modification of ACE-ARB agents after consent is not allowed unless for a safety reason and in consultation with the Medical Monitor prior to adding or modifying.
• Note: Subjects requiring additional medications to achieve the target blood pressure will use antihypertensive agents that have neutral effects on urinary proteinuria (e.g., Hydralazine or long-acting Dihydropyridine calcium channel blockers, etc.).
• Any subject taking Finerenone, Spironolactone, Eplerenone or any other mineralocorticoid receptor antagonists (MRAs), SGLT inhibitors, and non-dihydropyridine channel blockers (e.g., Diltiazem and Verapamil) must have been on a stable dose for ≥3 months prior to enrollment.
• Note: The addition or dose modification of these agents after consent is not allowed unless for a safety reason and in consultation with the Medical Monitor prior to adding or modifying.
• Any subject taking a medication that the Investigator believes could alter urinary protein or eGFR must agree to maintain a stable dose throughout the study period, including SGLT2 inhibitors.
• Note: Insulin and other diabetic agents can be adjusted for glycemic control.
• Have an eGFR by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula ≥20ml/min/1.73m\^2, at screening.
• For female subjects:

You may not qualify if:

• Subjects will be excluded from the trial if they meet any of the following criteria:
• Females who are pregnant or breastfeeding or plan to become pregnant or donate ova during the trial or 30 days after trial participation.
• Has a known allergy or intolerance to AECI, ARB, or Melanocortin peptides.
• Patients with a positive Serum Antigen/Antibody Hepatitis Panel (Hep B and C) and HIV antibody test Human Immunodeficiency Virus (HIV) antibody.
• Note: Patient with positive hepatitis C antibody but negative PCR test for active Hepatitis C viral shedding will be allowed to participate in the study. Patients with a positive Hepatitis B surface antigen antibody or core antigen antibody will be allowed to participate in the study. Patients with circulating hepatitis B surface antigen or have a positive PCR test for active hepatitis B virus will NOT be allowed to participate in the study.
• Patients with a known active history of alcohol dependence and/or drug use (with Cannabis exception) will be excluded from the study.
• Has significant medical illnesses that cannot be adequately controlled with appropriate therapy and may obscure toxicity, dangerously alter drug metabolism, or compromise the subject's ability to participate in the trial, as determined by the Investigator.
• Has current or prior receipt of bremelanotide therapy within the past year.
• Has used cyclosporine A, adrenocorticotropic hormones, long-term corticosteroids (\> 20 mg qd or its equivalent for \> 3 months), or cytotoxic agents within the past 3 months.
• Has a known positive ANA, or Anti-ds-DNA serology and considered by the site principal investigator to have active lupus will NOT be allowed to participate in the study. Patients with a positive RPR but a negative FTA test will be allowed to participate in the study. Patients with a positive Anti-PR3 or Anti-MPO antibody test and thought to have a clinical presentation consistent with ANCA vasculitis will NOT be allowed to participate in the study.
• Has a solitary kidney (acute kidney injury "AKI" risk) or is on dialysis.
• Has compromising heart failure or other cardiomyopathies in the opinion of the site Investigator.
• Has symptomatic and clinically significant hypotension or dehydration, as determined by the Investigator.
• Has taken any experimental drug or therapy within 28 days / 5 half-lives of trial treatment or concurrently participating in another clinical trial.
• Has a history of clinically significant bradycardia and/or a heart rate less than 50 bpm at screening.

Sponsors & Collaborators

• Palatin Technologies, Inc: lead

Study Sites (9)

California Institute of Renal Research

Chula Vista, California, 91910, United States

Location

California Institute of Renal Research DBA - Balboa Research

La Mesa, California, 91942, United States

Location

Georgia Nephrology, LLC DBA -GA Nephrology Research Institute

Decatur, Georgia, 30030, United States

Location

Georgia Nephrology, LLC [DBA] GA Nephrology Research Institute

Lawrenceville, Georgia, 30046, United States

Location

Brookview Hills Research Associates, LLC

Winston-Salem, North Carolina, 27103, United States

Location

Northeast Research Center, LLC

Bethlehem, Pennsylvania, 18017, United States

Location

Nephrotex Research Group

Dallas, Texas, 75231, United States

Location

Prolator Clinical Research Center

Houston, Texas, 77030, United States

Location

Clinical Advancement Center, PLLC

San Antonio, Texas, 78212, United States

Location

MeSH Terms

Conditions

Kidney Diseases

Interventions

bremelanotide; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Robert Jordan

  Palatin

  STUDY DIRECTOR

• James Tumlin, MD

  Georgia Nephrology Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This trial is a prospective, open-label trial to assess the efficacy of melanocortin receptor agonist bremelanotide (BMT) when administered with RAAS inhibition therapy after six months in subjects with Type II diabetic nephropathy.

Study Record Dates

• First Submitted: January 6, 2023
• First Posted: February 2, 2023
• Study Start: December 26, 2022
• Primary Completion: April 26, 2024
• Study Completion: April 26, 2024
• Last Updated: October 17, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)