Ataxia Telangiectasia Louis-BarPhase 2NCT04887311
MBM-01 (Tempol) for the Treatment of Ataxia Telangiectasia
A Phase 2 study testing MBM-01 in people with Ataxia Telangiectasia Louis-Bar and Ataxia Telangiectasia in Children, run by Matrix Biomed, Inc. at 1 site in United States.
Trial summary
Ataxia Telangiectasia (A-T) is an autosomal recessively inherited neurodegenerative disorder that also has dramatic effects on the immune and endocrine systems. The disorder results from mutations in the A-T mutated gene (ATM) leading to a loss in the production of the ATM protein. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Ataxia Telangiectasia Louis-Bar, Ataxia Telangiectasia in Children, Ataxia Telangiectasia
- What is being tested?
- MBM-01
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2021to Dec 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Have a confirmed diagnosis of A-T.
- Patients will either have a prior molecular confirmation or will be investigated;
- If female and of childbearing potential, must be using an effective birth-control method with a history of reliability for the individual patient;
- If a female with a male partner. If the male is of childbearing potential, adequate methods of contraception must be employed including use of condoms with spermicide. No sperm donation for 90 days until after the conclusion of the study;
- Body weight > 15 kg;
- Be able to participate for the full term of the clinical investigation;
- The patient and his/her parent/caregiver (if below the age of consent), or a legal representative, has provided written informed consent to participate. If consent is provided solely by the caregiver in accordance with local regulations, the patient must provide assent to participate in the study
Who cannot join
- Females that are
- pregnant, or are breast-feeding;
- Females of childbearing potential who do not use adequate birth control, as determined by their Health Care Provider;
- Patients with severe vision or hearing impairment (that is not corrected by glasses or hearing aids) that, at the investigator's discretion, interferes with their ability to perform study assessments;
- Patients who have been diagnosed with arthritis or other musculoskeletal disorders affecting joints, muscles, ligaments, and/or nerves that by themselves affects patient's mobility and, at the investigator's discretion, interferes with their ability to perform study assessments;
- A disability that may prevent the patient from completing all study requirements;
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- Severe or unstable pulmonary disease;
- Uncontrolled diabetes. Patients with diabetes that has been stabilized (i.e. no hypoglycemic or hyperglycemic episodes in the past 3 months) will be eligible;
- Current neoplastic disease or previous neoplastic disease not in remission for at least 2 years;
- Has participated in any other trial with an investigational drug and received a dose within 30 days;
- Requires any concomitant medication prohibited by the protocol;
- Any other severe, unstable, or serious disease or condition that in the Investigator's opinion would put the patient at risk for imminent life-threatening morbidity, need for hospitalization, or mortality; and
- Evidence of significant medical illness, or psychiatric illness/social situation that would, in the investigator's judgment, make the patient inappropriate for this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Health Science Center at Houston
Houston, Texas, 77030
Nick Russo, MD
Nicholas Russo, MD
About this study
Official title: An Open Label Study to Assess the Safety and Efficacy of MBM-01 for the Treatment of Ataxia Telangiectasia
Ataxia Telangiectasia (A-T) is an autosomal recessively inherited neurodegenerative disorder that also has dramatic effects on the immune and endocrine systems. The disorder results from mutations in the A-T mutated gene (ATM) leading to a loss in the production of the ATM protein.
The active compound in MBM-01 (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) may substitute for the loss of ATM by protecting cells from DNA damage, preventing and reducing oxidative damage, triggering an increase in cellular survival proteins, and preserving the brain and peripheral immune system.
Read the detailed description
Cells lacking ATM are left defenseless and unable to repair cellular damaged DNA, to exhibit normal cell cycle control, to effectively respond to oxidative damage, ionizing radiation, and, alkylating agents, and to maintain a healthy immune response among others. A-T patients have increased oxidative stress and significantly reduced total antioxidant levels. In an early study directed to oxidative stress in A-T patients, a decrease in the levels of total antioxidant capacity has been observed.
There is currently no cure for A-T, and current treatments are limited to palliative care. Therapies include rehabilitative care, infection prevention and treatment, and screening for pulmonary dysfunction and malignancies. Symptomatic treatments generally fall short and leave A-T patients debilitated and in a progressively wasting state. Patients suffering from A-T are in dire need of a treatment to alleviate the conditions of this disease. A drug product that can substitute for the loss of ATM has the potential to provide these patients with this critically unmet need. The active compound in MBM-01 has been shown to supplant the overall role of ATM by reducing oxidative stress, reducing DNA double strand breaks, and decreasing programmed cell death (in healthy cells). Accordingly, MBM-01 represents a potential breakthrough therapy for patients afflicted with A-T providing a multifactorial approached as evidenced by the following:
- Doubling the lifespan of otherwise short lived ATM-deficient mice ;
- Increasing NAD+, thereby decreasing the premature aging of A-T patients by reducing the severity of A-T neuropathology, normalizing neuromuscular function, delaying memory loss, and extending lifespan;
- Increasing the transcription factor BDNF and NRF2 to decrease neurodegeneration and activate cellular defense machinery via antioxidant genes;
- Maintaining and improving immune system function to ameliorate A-T symptoms ;
- Protecting DNA from damage and repairing the type of DNA damage observed in A-T patients;
- Preventing and reducing the type of oxidative stress observed in A-T patients;
- Increasing the lifespan of mice under various conditions and toxicities; and
- Decreasing tumorigenesis and carcinogenesis in general.
The study is a multi-center open label study to assess the efficacy of MBM-01 to treat ataxia telangiectasia. Patients will be assessed during three study phases: a baseline period, a 9-month treatment period, and a 3-month follow-up period. Patients will visit sites day 0, month 3, month 6, and month 9 for safety labs and efficacy assessments.
Dosing will follow a weight-tiered dosing schedule administered orally QD via premarked medicine cups. Patients will be administered study drug daily, 7-days a week. The patients will be placed into one of four dosing groups.
- Being tested
- MBM-01
- Medical subject headings
- Ataxia Telangiectasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MBM-01Drug
Also called Tempol oral solution
Patients will be administered study drug daily for 9 months QD via premarked medicine cups.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Group 1 Patients ≥13 years old will receive a total daily dose of 1200 mg/day.
Group 2 - Group 4
Patients 4-12 years old will receive group weight-tiered doses at 17 mg/kg:
Group 2
* Patients aged 4-12 years weighing 15kg to <25 kg will take 340 mg/day. Group 3
* Patients aged 4-12 years weighing 25kg to <35 kg will take 510 mg/day. Group 4
* Patients aged 4-12 years weighing ≥35 kg will take 850 mg/day. Receives: Drug: MBM-01 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in International Cooperative Ataxia Rating Scale (ICARS)
The ICARS is a 19 item rating scale of ataxia with the total score ranging from 0 to 100. A score of 0 means normal and higher scores represent worsened disease.
Measured: ICARS evaluations will be taken at baseline, month 3, month 6, and month 9.
Secondary outcomes (10)
Change in Nine Hole Peg Test (9HPT) Baseline (Day 1) to end of treatment with MBM-01
Measured: The change in 9HPT will be taken at baseline, month 3, month 6, and month 9.
Change in Timed 25 Feet Walking Test (T25FW)
The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time, in seconds, is calculated from the initiation of the instruction to start and ends when the patient has reached the 25-foot mark. Baseline values are recorded twice.
Measured: T25FW will be assessed at baseline, month 3, month 6, and month 9.
Change in total antioxidant capacity
The plasma antioxidant capacity will be determined by the trolox-equivalent antioxidant capacity test (TEAC)
Measured: (TEAC) taken at baseline, month 3, month 6, and month 9
Change in Total Plasma Lipid Peroxides
Measured: Change in total plasma lipid peroxide levels taken at baseline, month 3, month 6, and month 9.
Change in GSH/glutathione Disulfide (GSSG) Concentration Ratio
GSH concentrations will be compared to glutathione disulfide.
Measured: taken at baseline, month 3, month 6, and month 9.
Change in lymphocyte counts (CD3)
Measured: Change in serum lymphocyte counts (CD3) taken at baseline, month 3, month 6, and month 9
Change in lymphocyte counts (CD4)
Measured: Change in serum lymphocyte counts (CD4) taken at baseline, month 3, month 6, and month 9
Change in lymphocyte counts (CD8)
Measured: Change in serum lymphocyte counts (CD8) taken at baseline, month 3, month 6, and month 9
Change in lymphocyte counts (CD19)
Measured: Change in serum lymphocyte counts (CD19) taken at baseline, month 3, month 6, and month 9
Change 8-hydroxy-2- Deoxyguanosine (8-OHdG)
Evaluation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct levels in human peripheral blood lymphocytes taken at baseline, month 3, month 6, and month 9.
Measured: Taken at baseline, month 3, month 6, and month 9.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2021
- Study startJul 2021 (estimated)
- Primary completionJun 2022 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ataxia Telangiectasia Louis-BarStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Matrix Biomed, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04887311
- Sponsor's protocol ID
- MBI-09-01
- Status last verified
- May 2021
- First submitted
- 5 May 2021
- Last updated
- 17 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Publications
Schubert R, Erker L, Barlow C, Yakushiji H, Larson D, Russo A, Mitchell JB, Wynshaw-Boris A. Cancer chemoprevention by the antioxidant tempol in Atm-deficient mice. Hum Mol Genet. 2004 Aug 15;13(16):1793-802. doi: 10.1093/hmg/ddh189. Epub 2004 Jun 22.
PubMed 15213104
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Study to Assess the Safety and Efficacy of MBM-01 for the Treatment of Ataxia Telangiectasia
- ClinicalTrials.gov ID
- NCT04887311
- Acronym / sponsor ID
- MBI-09-01
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Matrix Biomed, Inc.Industry (pharma, biotech, devices)
- Collaborators
- The University of Texas Health Science Center, Houston
- Study start
- Jul 2021 (estimated)
- Primary completion
- Jun 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 14 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ataxia Telangiectasia (A-T) is an autosomal recessively inherited neurodegenerative disorder that also has dramatic effects on the immune and endocrine systems. The disorder results from mutations in the A-T mutated gene (ATM) leading to a loss in the production of the ATM protein.
The active compound in MBM-01 (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) may substitute for the loss of ATM by protecting cells from DNA damage, preventing and reducing oxidative damage, triggering an increase in cellular survival proteins, and preserving the brain and peripheral immune system.
Detailed description
Cells lacking ATM are left defenseless and unable to repair cellular damaged DNA, to exhibit normal cell cycle control, to effectively respond to oxidative damage, ionizing radiation, and, alkylating agents, and to maintain a healthy immune response among others. A-T patients have increased oxidative stress and significantly reduced total antioxidant levels. In an early study directed to oxidative stress in A-T patients, a decrease in the levels of total antioxidant capacity has been observed.
There is currently no cure for A-T, and current treatments are limited to palliative care. Therapies include rehabilitative care, infection prevention and treatment, and screening for pulmonary dysfunction and malignancies. Symptomatic treatments generally fall short and leave A-T patients debilitated and in a progressively wasting state. Patients suffering from A-T are in dire need of a treatment to alleviate the conditions of this disease. A drug product that can substitute for the loss of ATM has the potential to provide these patients with this critically unmet need. The active compound in MBM-01 has been shown to supplant the overall role of ATM by reducing oxidative stress, reducing DNA double strand breaks, and decreasing programmed cell death (in healthy cells). Accordingly, MBM-01 represents a potential breakthrough therapy for patients afflicted with A-T providing a multifactorial approached as evidenced by the following:
- Doubling the lifespan of otherwise short lived ATM-deficient mice ;
- Increasing NAD+, thereby decreasing the premature aging of A-T patients by reducing the severity of A-T neuropathology, normalizing neuromuscular function, delaying memory loss, and extending lifespan;
- Increasing the transcription factor BDNF and NRF2 to decrease neurodegeneration and activate cellular defense machinery via antioxidant genes;
- Maintaining and improving immune system function to ameliorate A-T symptoms ;
- Protecting DNA from damage and repairing the type of DNA damage observed in A-T patients;
- Preventing and reducing the type of oxidative stress observed in A-T patients;
- Increasing the lifespan of mice under various conditions and toxicities; and
- Decreasing tumorigenesis and carcinogenesis in general.
The study is a multi-center open label study to assess the efficacy of MBM-01 to treat ataxia telangiectasia. Patients will be assessed during three study phases: a baseline period, a 9-month treatment period, and a 3-month follow-up period. Patients will visit sites day 0, month 3, month 6, and month 9 for safety labs and efficacy assessments.
Dosing will follow a weight-tiered dosing schedule administered orally QD via premarked medicine cups. Patients will be administered study drug daily, 7-days a week. The patients will be placed into one of four dosing groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: MBM-01Group 1 Patients ≥13 years old will receive a total daily dose of 1200 mg/day. Group 2 - Group 4 Patients 4-12 years old will receive group weight-tiered doses at 17 mg/kg: Group 2 * Patients aged 4-12 years weighing 15kg to <25 kg will take 340 mg/day. Group 3 * Patients aged 4-12 years weighing 25kg to <35 kg will take 510 mg/day. Group 4 * Patients aged 4-12 years weighing ≥35 kg will take 850 mg/day. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Have a confirmed diagnosis of A-T.
- If female and of childbearing potential, must be using an effective birth-control method with a history of reliability for the individual patient;
- If a female with a male partner. If the male is of childbearing potential, adequate methods of contraception must be employed including use of condoms with spermicide. No sperm donation for 90 days until after the conclusion of the study;
- Body weight > 15 kg;
- Be able to participate for the full term of the clinical investigation;
Key exclusion criteria (13 listed)
- Females that are
- Females of childbearing potential who do not use adequate birth control, as determined by their Health Care Provider;
- Patients with severe vision or hearing impairment (that is not corrected by glasses or hearing aids) that, at the investigator's discretion, interferes with their ability to perform study assessments;
- Patients who have been diagnosed with arthritis or other musculoskeletal disorders affecting joints, muscles, ligaments, and/or nerves that by themselves affects patient's mobility and, at the investigator's discretion, interferes with their ability to perform study assessments;
- A disability that may prevent the patient from completing all study requirements;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MBM-01Also: Tempol oral solutionPatients will be administered study drug daily for 9 months QD via premarked medicine cups. | Drug | Cohort 1 |
Primary outcome
Change in International Cooperative Ataxia Rating Scale (ICARS)
Time frame: ICARS evaluations will be taken at baseline, month 3, month 6, and month 9.
The ICARS is a 19 item rating scale of ataxia with the total score ranging from 0 to 100. A score of 0 means normal and higher scores represent worsened disease.
10 secondary outcomes
Change in Nine Hole Peg Test (9HPT) Baseline (Day 1) to end of treatment with MBM-01
Time frame: The change in 9HPT will be taken at baseline, month 3, month 6, and month 9.
Change in Timed 25 Feet Walking Test (T25FW)
Time frame: T25FW will be assessed at baseline, month 3, month 6, and month 9.
Change in total antioxidant capacity
Time frame: (TEAC) taken at baseline, month 3, month 6, and month 9
Change in Total Plasma Lipid Peroxides
Time frame: Change in total plasma lipid peroxide levels taken at baseline, month 3, month 6, and month 9.
Change in GSH/glutathione Disulfide (GSSG) Concentration Ratio
Time frame: taken at baseline, month 3, month 6, and month 9.
Change in lymphocyte counts (CD3)
Time frame: Change in serum lymphocyte counts (CD3) taken at baseline, month 3, month 6, and month 9
Change in lymphocyte counts (CD4)
Time frame: Change in serum lymphocyte counts (CD4) taken at baseline, month 3, month 6, and month 9
Change in lymphocyte counts (CD8)
Time frame: Change in serum lymphocyte counts (CD8) taken at baseline, month 3, month 6, and month 9
Change in lymphocyte counts (CD19)
Time frame: Change in serum lymphocyte counts (CD19) taken at baseline, month 3, month 6, and month 9
Change 8-hydroxy-2- Deoxyguanosine (8-OHdG)
Time frame: Taken at baseline, month 3, month 6, and month 9.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2021.
- Background: PubMed 15213104Schubert R, Erker L, Barlow C, Yakushiji H, Larson D, Russo A, Mitchell JB, Wynshaw-Boris A. Cancer chemoprevention by the antioxidant tempol in Atm-deficient mice. Hum Mol Genet. 2004 Aug 15;13(16):1793-802. doi: 10.1093/hmg/ddh189. Epub 2004 Jun 22.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MBM-01 in people with Ataxia Telangiectasia Louis-Bar and Ataxia Telangiectasia in Children, run by Matrix Biomed, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Benji Crane (6264376506, bjcrane@matrixbiomed.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in International Cooperative Ataxia Rating Scale (ICARS) (time frame: ICARS evaluations will be taken at baseline, month 3, month 6, and month 9.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04887311, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2021.