GM604 Phase 2A Randomized Double-blind Placebo Controlled Pilot Trial in Amyotrophic Lateral Disease (ALS)

NCT01854294 | Completed Phase 2

• 1 other identifier: GALS 001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

GM604 is an endogenous human embryonic stage neural regulatory and signaling peptide that controls the development, monitoring and correction of the human nervous system. Neurological diseases are multisystem, multifactorial, and single target drugs are ineffective. Genervon's Master Regulators play a significant role in embryonic/fetal nervous system development and are potent disease modification drug candidates modulating many pathways including inflammation, apoptotic, and hypoxia. The study drug is an regulatory peptide with a sequence identical to one of the active sites of human Motoneuronotrophic Factor and is manufactured by solid phase synthesis. Pre-clinical research indicates it to be a neuro-protective agent in animal models of ALS, motorneuron diseases, PD, other neuro-degenerative diseases and stroke. GM604 controls and modulates over many known and significant ALS genes with positive effects interactively and dynamically through multiple pathways, and up to twenty-two biological processes, including neuro-protection, neurogenesis, neural development, neuronal signaling, neural transport, and other processes. GM6 is not a cocktail of drugs, but one master regulator peptide drug that functions through multiple pathways. Genervon hypothesized that studying the biomarkers of protein expressions of these ALS genes such as superoxide dismutase 1 (SOD1) and the protein expression of substances such as tau, neurofilament - heavy (NF-H), Cystatin C which were indications of degeneration of neuron in the CSF collected from ALS patients will provide information of the possible GM604's mechanisms of action in treating ALS. 1. This pilot trial is designed to test proof of principle, i.e. determine if a 2-week IV bolus treatment with this agent can (1) change ALS protein expression (target biomarkers and efficacy biomarkers) after treatment (2) have preliminary effects measures of ALS disease clinical progression. Study Objectives are:

1. 1.To test the safety and tolerability of GM604 in a population of ALS patients.
2. 2.To test for changes in ALS biomarkers before and after treatment.
3. 3.To determine preliminary effects of injections of GM604 on measures of ALS disease biomarkers and clinical progression

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; motorneuron disease; Central Nervous System (CNS) disease; neurodegeneration; neuroprotective; mechanisms of action; pathways; biomarkers; Cerebral Spinal Fluid (CSF); blood biomarkers; multi-factorial; multisystem; single target; pathogenic mechanisms; Protein Bands Selection by Function; in silico analysis; active site; protein; peptide; embryonic stage; endogenous; master regulators; fetal development; embryonic development; common pathways; Blood Brain Barrier (BBB); anti-inflammatory; anti-apoptotic; anti-oxidative; regenerative; distress signals; neurotrophin; Motoneuronotrophic factor (MNTF); ALS model; life span; disease onset; grip strength; protein expression; DNA microarray; differential expression; Phase 1 clinical trial; rare disease; common underlying pathogenic mechanisms; neurological deficits; gene mutation; misfolded proteins; inadvertent errors; modulation of genes; master regulator peptide drug; ALS related genes; mitochondria dysfunction; excitotoxicity; axonal transport; oxidative stress; protein aggregation; pathogenesis; target biomarkers; efficacy biomarkers

Outcome Measures

Primary Outcomes (3)

• Efficacy by percent change in biomarker in th CSF at week 12 from baseline

  Efficacy by percent change in biomarker in the CSF at week 12 from baseline: (a) Efficacy biomarkers (b) Target biomarkers (c) Efficacy/target biomarkers

  baseline, week 2, week 12

• Safety by measuring 1. adverse event frequency and severity, changes in vital signs, clinical laboratory values. 2. Serious adverse event frequency

  Safety: 1. adverse event frequency and severity, changes in vital signs, clinical laboratory values. 2. Serious adverse event frequency

  baseline, week 2, week 12

• Tolerability by measuring the ability to complete the first 2 weeks of active treatment in the study

  Tolerability: The ability to complete the first 2 weeks of active treatment in the study

  Baseline, week 2, week 12

Secondary Outcomes (6)

• ALSFRS-R (Amyotrophic Laeral Sclerosis Functional Rating Scale - Revised)

  Symptom onset, screening, baseline, week 2, week 6, week 12

• Forced Vital Capacity (FVC)

  Symptom onset, baseline, week 2, week 6, week 12

• Time Up and Go (TUG)

  Symptom onset, baseline, week 2, week 6, week 12

• muscle strength

  Symptom onset, baseline, week 2, week 6, week 12

• Biomarker in blood

  baseline, week 2, week 6, week 12

Other Outcomes (2)

• comparison of slopes (change in the rate of decline)of disease progression

  Symptom onset, baseline, week 2, week 6, week 12

• stratification of patients by symptoms

  Symptom onset, baseline, week 2, week 6, week 12

Study Arms (2)

GM604 treated

EXPERIMENTAL

8 subjects will receive GM604. Each GM604 treated subject will receive a slow IV bolus injection (\~1min) of 6.4 mL (320mg @50 mg/mL=6.4 mL) for each dose. A total of 6 doses will be administered over two weeks (on Mondays, Wednesdays and Fridays for the first 2 weeks).

Drug: GM604

Placebo comparator

PLACEBO COMPARATOR

4 subjects will receive placebo. 6.4 mL Bacteriostatic saline will be used for the Placebo group. Injections will be given to the subject in the same manner as in GM604 treated group. A total of 6 doses will be administered over two weeks (on Mondays, Wednesdays and Fridays for the first 2 weeks).

Drug: Placebo comparator

Interventions

GM604 DRUG

GM604 treated group subject will receive a slow IV bolus injection (\~1min) of 6.4 mL (320mg @50 mg/mL=6.4 mL) for each dose. A total of 6 doses will be administered over two weeks (on Mondays, Wednesdays and Fridays for the first 2 weeks).

Also known as: GM6, GM602, GM608

GM604 treated

Placebo comparator DRUG

Placebo comparator group subject will receive a slow IV bolus injection (\~1min) of 6.4 mL bacteriostatic saline for each dose. A total of 6 doses will be administered over two weeks (on Mondays, Wednesdays and Fridays for the first 2 weeks).

Also known as: Bacteriostatic saline

Placebo comparator

Eligibility Criteria

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

You may qualify if:

• Patients with ALS: Familial and Sporadic ALS, with symptom onset \< or equal to 24 months.
• At least 18 years of age
• Subjects meet the El Escorial criteria of definite criteria for a diagnosis of ALS.
• Subjects can be on a stable dose of riluzole for at least a month or not taking or initiating riluzole for the duration of the trial.
• Not on any experimental medication for the last 1 month or five times the half-life of experimental medication.
• At screening, must have a Forced Vital Capacity (FVC) ≥ 65% of predicted capacity for age, height and gender.
• Have fully completed informed consent form
• Ability to comply with study procedures
• Women of child-bearing age must be on birth control. Pregnancy test should be done in women in child bearing age.
• Medically safe to have lumbar puncture to collect CSF

You may not qualify if:

• History of liver disease, severe renal failure, diabetes, coronary heart disease, cancer
• Clinically significant EKG abnormality at screening
• Any comorbid condition which would make completion of the trial unlikely
• FVC \< 65%
• Presence of a bleeding disorder
• Allergy to local anesthetics
• Problem with CSF pressure
• Topical or other skin infection at the lumbar puncture site
• BMI \> 32 kg/m2
• Medical or surgical conditions in which a lumbar puncture is contraindicated
• Use of any anti-platelet or anticoagulant drugs, such as plavix, aggrenox, ticlid, warfarin or coumadin

Sponsors & Collaborators

• Genervon Biopharmaceuticals, LLC: lead
• Columbia University: collaborator
• Massachusetts General Hospital: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Columbia Medical Center NY

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Central Nervous System Diseases; Nerve Degeneration; Rare Diseases; Mitochondrial Diseases

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Study Officials

• Hiroshi Mitsumoto, MD

  Columbia Medical Center NY

  PRINCIPAL INVESTIGATOR

• Merit Cudkowicz, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2013
• First Posted: May 15, 2013
• Study Start: August 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: July 1, 2014
• Last Updated: April 27, 2021

Record last verified: 2019-07

Locations

US (2)