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X Linked Myotubular MyopathyPhase 1/2TAM4MTMNCT04915846

Tamoxifen Therapy for Myotubular Myopathy

A Phase 1/2 study testing ApoTamox 10mg in people with X Linked Myotubular Myopathy, run by James Dowling at 4 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a phase 1 / 2, randomized, double-blinded, single cross-over study, with a washout period between treatment regimens, to test the efficacy and safety of tamoxifen therapy to improve motor and respiratory function in males with XLMTM. Read more about this study

Who is it for?
Ages 6 months and older, men only
Conditions the study is for
X Linked Myotubular Myopathy
What is being tested?
ApoTamox 10mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
6 participants
Where
4 sitesin 3 countries
Study dates
18 Dec 2020to 9 May 2024
Phase
Phase 1/2
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 6 months and older
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Male
  • Patients ages 6 months and older may participate.
  • XLMTM resulting from a confirmed mutation in the Myotubularin 1 (MTM1) gene
  • Patients over 18 years of age and parent(s)/legal guardian(s) of patients <18 years of age must provide written informed consent prior to participating in the study and informed assent will be obtained from minors, or at least 7 years of age when required by regulation.
  • Willing and able to comply with all protocol requirements and procedures.

Who cannot join

  • Other disease which may significantly interfere with the assessment of myotubular myopathy (MTM) and is clearly not related to the disease, at the discretion of the qualified investigator.
  • Has undergone surgery or hospitalization < 3 months before starting TAM4MTM (at t = -3 months), or has surgery scheduled during the 18 months of participation in TAM4MTM, which will impede motor assessments in the opinion of the Investigator.
  • Has a history of thromboembolic events
  • Currently enrolled in a treatment study for XLMTM or receiving treatment with an experimental therapy other than pyridostigmine.
  • Treatment with pyridostigmine for < 6 weeks duration (must be greater than 6 weeks to be included in TAM4MTM).
  • Use of concomitant medication known to inhibit CYP2D6 and/or CYP3A4, including clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal and grapefruit, paroxetine, troleandomycin, rifampin, phenobarbital, aminoglutethimide, medroxyprogesterone, amiodarone, haloperidol, indinavir, ritonavir, quinidine, rifampicin, or any selective serotonin reuptake inhibitor (SSRI).
  • Subject has a contraindication to tamoxifen or its ingredients

Trial locations and contacts

4 sites in 3 countries.

4 sites in 3 countries

United States2 sites

  • Ann and Robert H. Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60611

  • National Institutes of Health

    Rockville, Maryland, 20892

Other trials in United States

Canada1 site

  • Hospital for Sick Children

    Toronto, Ontario, M5G1X8

Other trials in Canada

United Kingdom1 site

  • Great Ormond Street Hospital for Children

    London, WC1N 3JH

Other trials in United Kingdom

About this study

Official title: TAM4MTM: a Phase 1/2 Randomized, Placebo-Controlled, Double-Blinded, Single Crossover Study to Determine the Safety and Efficacy of Tamoxifen Therapy for Myotubular Myopathy (XLMTM)

This is a phase 1 / 2, randomized, double-blinded, single cross-over study, with a washout period between treatment regimens, to test the efficacy and safety of tamoxifen therapy to improve motor and respiratory function in males with XLMTM.

Read the detailed description

Pre-clinical studies in Mtm1 knockout mice (a model of XLMTM) demonstrated prolonged survival, increased motor function (including muscle strength), and improved muscle histopathology with tamoxifen treatment. Based on these data, and the known safety profile of the drug in humans, we hypothesize that tamoxifen treatment will be safe and will improve motor and respiratory function in XLMTM patients. This is a randomized, double-blinded, single crossover clinical trial to test this hypothesis and determine the safety and efficacy of tamoxifen in improving motor and respiratory function in MTM patients. Each subject will serve as his own control during the placebo phase of the study. As treatments for XLMTM are current not available, this study addresses a critical unmet need by testing a therapy that, if effective, may serve as a primary treatment, or in the future as an adjunct to other therapies in development.

Being tested
ApoTamox 10mg, Placebo
Keywords
tamoxifen, X-linked myotubular myopathy
Medical subject headings
Myopathies, Structural, Congenital

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ApoTamox 10mgDrug

    Also called Tamoxifen Citrate

    All participants will receive tamoxifen (ApoTamox) for approximately 6 months (6 months + 1 week). Participants and study staff will be blinded as to whether the participants are starting with the placebo or the drug. Depending on randomization, drug or placebo will be dispensed at the end of the t=0 study visit (Phase 1). Dosing will commence the day after the t=0 study visit. At the end of Phase 1, participants will enter a 'washout' period, when they will cease treatment. After approximately 3 months of washout, participants will cross-over to the other treatment regimen and receive the other interventional product (IP) for the final 6 months of their study participation (Phase 2).

  • PlaceboDrug

    placebo comparator

Study groups in NCT04915846
Study groupRoleWhat they receive
Drug: ApoTamox 10mgExperimentalDrug: Tamoxifen (tamoxifen citrate); ApoTamox 10 mg tablets orally twice daily for 6 months
Receives: Drug: ApoTamox 10mg
PlaceboPlacebo comparatorPlacebo (no active ingredients) tablets orally twice daily for 6 months
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Motor Function Measure 32 (MFM32)

    Mean change from baseline of Motor Function Measure 32 for subjects aged 4 and older

    Measured: Baseline to 15 Months

  2. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders for subjects aged 2-4 years (CHOP INTEND)

    Mean change from baseline of Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders for subjects aged 2-4 years

    Measured: Baseline to 15 months

  3. 10 meter walk test

    Mean change from baseline in velocity in 10 meter walk test for ambulant participants

    Measured: Baseline to 15 months

Secondary outcomes (8)

  1. Change in pulmonary function testing scores 1) Forced Expiratory Volume in the first second

    Mean change from baseline in participants without invasive respiratory support

    Measured: Baseline to 15 months

  2. Change in pulmonary function testing scores 2) Forced Vital Capacity

    Mean change from baseline in participants without invasive respiratory support

    Measured: Baseline to 15 months

  3. Change in pulmonary function testing scores 3) Peak Cough Flow

    Mean change from baseline in participants without invasive respiratory support

    Measured: Baseline to 15 months

  4. Change in pulmonary function testing scores 4) Maximum Expiratory Pressure

    Mean change from baseline in participants without invasive respiratory support

    Measured: Baseline to 15 months

  5. Change in pulmonary function testing scores 5) Maximum Inspiratory Pressure or Sniff Inspiratory Pressure

    Mean change from baseline in participants without invasive respiratory support

    Measured: Baseline to 15 months

  6. invasive ventilation - time off ventilation

    Mean change in time off ventilator for participants dependent on invasive respiratory support

    Measured: Baseline to 15 months

  7. Incidence and severity of Adverse Events related to the treatment [ Time Frame: 15 Months ]

    Incidence of serious adverse events and adverse events throughout the study, as assessed by CTCAE v4.0

    Measured: Baseline to 15 months

  8. micro RNA 133a (miR133a)

    Assess miR133a as a biomarker of XLMTM

    Measured: Baseline to 15 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2021
  2. Study start18 Dec 2020
  3. Primary completion9 May 2024
  4. Study completion9 May 2024

Why it stopped: Study terminated due to safety concerns.

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
Double-blinded, placebo-controlled, single cross-over study with washout period before cross-over
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04915846
Sponsor's protocol ID
TAM4MTM / OZM-098
Acronym
TAM4MTM
Status last verified
Mar 2024
First submitted
6 May 2021
Last updated
19 Sep 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Amburgey K, Tsuchiya E, de Chastonay S, Glueck M, Alverez R, Nguyen CT, Rutkowski A, Hornyak J, Beggs AH, Dowling JJ. A natural history study of X-linked myotubular myopathy. Neurology. 2017 Sep 26;89(13):1355-1364. doi: 10.1212/WNL.0000000000004415. Epub 2017 Aug 25.

    PubMed 28842446

  • Maani N, Sabha N, Rezai K, Ramani A, Groom L, Eltayeb N, Mavandadnejad F, Pang A, Russo G, Brudno M, Haucke V, Dirksen RT, Dowling JJ. Tamoxifen therapy in a murine model of myotubular myopathy. Nat Commun. 2018 Nov 19;9(1):4849. doi: 10.1038/s41467-018-07057-5.

    PubMed 30451841

  • Gayi E, Neff LA, Massana Munoz X, Ismail HM, Sierra M, Mercier T, Decosterd LA, Laporte J, Cowling BS, Dorchies OM, Scapozza L. Tamoxifen prolongs survival and alleviates symptoms in mice with fatal X-linked myotubular myopathy. Nat Commun. 2018 Nov 19;9(1):4848. doi: 10.1038/s41467-018-07058-4.

    PubMed 30451843

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ApoTamox 10mg in people with X Linked Myotubular Myopathy, run by James Dowling at 4 sites in 3 countries.

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 5 inclusion and 7 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: stopped early, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, Canada, United Kingdom. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study was stopped early (reason given: Study terminated due to safety concerns.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Motor Function Measure 32 (MFM32) (time frame: Baseline to 15 Months). The study lists 3 primary outcomes in all. 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 NCT04915846, which also lists 3 linked publications.

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 19 Sep 2024; AzTrials last refreshed its copy on 6 Nov 2026.

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