Gleolan for Visualization of Newly Diagnosed or Recurrent Meningioma (MEN-301)

A Phase 3 Multicenter Study of Gleolan (Aminolevulinic Acid Hydrochloride) to Enhance Visualization of Tumor in Patients With Newly Diagnosed or Recurrent Meningiomas

This Phase 3 open-label single-arm study is designed to investigate the safety, diagnostic performance, and clinical usefulness of Gleolan for the real time detection and visualization of meningiomas during tumor resection surgery. The study is planned to run for 15 months with individual study participation lasting for approximately 2 months.

Study Overview

• Status: Completed
• Conditions: Meningioma
• Intervention / Treatment: Drug: Gleolan

Detailed Description

This Phase 3 open-label single-arm study is designed to investigate the safety, diagnostic performance, and clinical usefulness of the imaging agent Gleolan™ (Aminolevulinic Acid Hydrochloride, ALA HCl, ALA, 5-ALA), an orally administered imaging agent for the real time detection and visualization of meningiomas during tumor resection surgery. ALA is a prodrug that is metabolized intracellularly to form the fluorescent molecule Protoporphyrin IX (PpIX). The exogenous application of ALA leads to a highly selective accumulation of PpIX in tumor cells. Following excitation with blue light (BL) (λ = 375 - 440 nm), the PpIX, which has accumulated selectively in tumor tissue, emits a red-violet light. This phenomenon allows for the real-time visualization of tumor tissue during resection surgery.

Patients about to undergo resection for suspected meningioma [World Health Organization (WHO) Grade I, II, III] will be screened and informed consent will be obtained prior to surgery and prior to study participation. Eligible study participants will receive an oral solution of Gleolan (20 mg/kg body weight) 3 hours, (target range 2-4 hours) prior to anesthesia, and then undergo surgery for meningioma resection. During the surgery, the surgeon will use a microscope equipped with WL and BL for visualization of Gleolan-induced PpIX fluorescence for the selection of protocol-driven tissue locations and to assess fluorescence status.

Study participants will be evaluated within 48 hours post procedure, 2 weeks post procedure, and 6 weeks post procedure for study safety assessment.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna
• Germany
  • Münster, Germany
    • University Hospital Münster
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC
    • Orange, California, United States, 92868
      • Providence St. Joseph Hospital
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
  • Florida
    • Coral Gables, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33176
      • Baptist Health South Florida
  • Illinois
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • New York
    • Brooklyn, New York, United States, 11220
      • NYU Langone Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania- Penn Medicine
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. A pre-operative MRI within ≤ 90 days of study enrollment documenting a suspected meningioma or suspected recurrence of a meningioma for which a meningioma resection is indicated and has been planned.
2. Adult age ≥ 18 years.
3. Patient must have normal organ and bone marrow function and be appropriate surgical candidates per site SOC.

4. Patient must have recording of each parameter as defined below:

   Bilirubin Below upper limit of normal AST (SGOT) < 2.5 X institutional upper limit of normal ALT (SGPT) < 2.5 X institutional upper limit of normal Creatinine Below upper limit of normal OR Creatinine clearance >60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal

5. The patient must demonstrate the ability to understand the informed consent document and the willingness and ability to sign a written informed consent document. The study consent documents will be prepared in English and German and Spanish. Translation for non-English, non-German, or non-Spanish speaking participants will be provided as appropriate by institution, as required.
6. WOCBP and men participating must agree to use highly effective forms of contraception, and men must also agree not to donate sperm for the duration of treatment, and for at least 42 days after the one time use of the study drug.

Exclusion Criteria:

1. History of allergic reactions attributed to compounds of similar chemical/biologic composition to Gleolan.
2. Known or documented personal or family history of porphyria.
3. Uncontrolled concurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness.
4. Patient has had a meningioma resection or radiation treatment within 90 days of informed consent.
5. Social or medical situations that would limit compliance with study requirements (e.g. ability to travel for follow-up or inability to obtain appropriate pre-op MRI (e.g. cardiac pacemaker).
6. Women who are pregnant or plan to become pregnant during study participation.
7. Prior history of gastrointestinal perforation, diverticulitis, and or/peptic ulcer disease within 90 days of informed consent.
8. Simultaneous participation in another clinical study or participation in another clinical study in the 30 days directly preceding treatment or within 5 plasma half-life of the preceding study drug, whatever is longer.
9. Simultaneous use of other potentially phototoxic substances (St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulphonamides, quinolones and tetracyclines), and topical preparations containing ALA for 24 hours during the perioperative period (see MOPS for detailed list).
10. Unwillingness by patient to sign consent or return for subsequent visits following surgery.
11. Any condition that in the opinion of the Investigator would exclude the patient as a viable candidate for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm; Open-label, intra-subject control	Drug: Gleolan; One time oral dose on day of surgery (20 mg/kg bodyweight); Other Names: Aminolevulinic Acid Hydrochloride / ALA / ALA HCI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Participants Who Had at Least 1 Indeterminate Tissue or Unexpected Fluorescent End of Surgery (EOS) Tissue Where Gleolan-induced PpIX Fluorescence Status is Consistent With Histology (i.e., True Positive or True Negative for Meningioma).	Responders are defined as the percentage of participants among all participants receiving Gleolan (the Intent to Image Population) who had at least one indeterminate tissue or unexpected fluorescent end of surgery (EOS) tissue where Gleolan-induced PpIX fluorescence status was consistent with central laboratory histology. For a participant to be considered a success, only biopsies considered 'non-obvious' for tumor status by an external panel of neurosurgeons who reviewed videos and images were eligible to be assessed in the numerator. A two-sided 95% confidence interval was calculated using the Wilson (score) method. The lower bound of the confidence interval was tested against a null hypothesis value of 30%. A modified worst-case imputation was used for missing data.	Surgery (Day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Predicted Value (PPV) of Gleolan-induced PpIX Fluorescence Status of Biopsied Tissue Locations at the Margin of the Tumor [Indeterminate Tissues and Unexpected Fluorescent EOS Tissues (Combined)].	PPV calculation considers both indeterminate and unexpected fluorescent end-of-surgery tissues. Generalized Estimating Equation (GEE) models that take into account the correlation (clustering) of the biopsies within a participant were used to calculate the estimates and two-sided 95% confidence intervals. The models used a binomial distribution function with an exchangeable working correlation matrix and utilized a robust variance estimator. PPV = TP/(TP+FP) TP = True Positive; FP = False Positive; The truth standard was determined via central histopathology.	Surgery (Day 1)
Negative Predicted Value (NPV) of Gleolan-induced PpIX Fluorescence Status of Biopsied Tissue Locations at the Margin of the Tumor [Indeterminate Tissues].	NPV calculation considered indeterminate tissues only since unexpected fluorescent end-of-surgery tissues were, by definition, fluorescence positive. Generalized Estimating Equation (GEE) models that take into account the correlation (clustering) of the biopsies within a participant were used to calculate the estimates and two-sided 95% confidence intervals. The models used a binomial distribution function with an exchangeable working correlation matrix and utilized a robust variance estimator. NPV = TN/(TN+FN) TN = True Negative; FN = False Negative; The truth standard was determined via central histopathology.	Surgery (Day 1)
Positive Predictive Value of Single Bulk Tumor Sample Obtained From Each Participant.	PPV (PPV=TP/(TP+FP)) of Gleolan-induced PpIX fluorescence status of biopsied tissue locations of bulk/core meningioma tumor	Surgery (Day 1)

Collaborators and Investigators

• Sponsor: NX Development Corp
• Investigators: Principal Investigator: Walter Stummer, MD, Universitatsklinikum Munster; Principal Investigator: Bernard Bendok, MD, Mayo Clinic

Publications and helpful links

General Publications

• Stummer W, Holling M, Bendok BR, Vogelbaum MA, Cox A, Renfrow SL, Widhalm G, Ezrin A, DeSena S, Sackman ML, Wyse JW. The NXDC-MEN-301 Study on 5-ALA for Meningiomas Surgery: An Innovative Study Design for the Assessing the Benefit of Intra-Operative Fluorescence Imaging. Brain Sci. 2022 Aug 6;12(8):1044. doi: 10.3390/brainsci12081044.

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2020
• Primary Completion (Actual): November 7, 2022
• Study Completion (Actual): December 13, 2022

Study Registration Dates

• First Submitted: March 9, 2020
• First Submitted That Met QC Criteria: March 9, 2020
• First Posted (Actual): March 12, 2020

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: ALA; meningioma; fluorescence guided surgery; Gleolan
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Meningioma; Amino Acids, Peptides, and Proteins; Organic Chemicals; Carboxylic Acids; Amino Acids; Keto Acids; Levulinic Acids; Aminolevulinic Acid
• Other Study ID Numbers: NXDC-MEN-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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