Tamoxifen Therapy for Myotubular Myopathy (TAM4MTM)

James Dowling

Status and phase: Terminated; Phase 2; Phase 1

Conditions: X Linked Myotubular Myopathy

Treatments: Drug: Placebo; Drug: ApoTamox 10mg

Study type: Interventional

Funder types: Other

Identifiers

NCT04915846

TAM4MTM / OZM-098

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6 patients

Sex: Male

Ages: 6+ months old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

INCLUSION CRITERIA

1. Male
2. Patients ages 6 months and older may participate.
3. XLMTM resulting from a confirmed mutation in the Myotubularin 1 (MTM1) gene
4. 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.
5. Willing and able to comply with all protocol requirements and procedures.

EXCLUSION CRITERIA

1. 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.
2. 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.
3. Has a history of thromboembolic events
4. Currently enrolled in a treatment study for XLMTM or receiving treatment with an experimental therapy other than pyridostigmine.
5. Treatment with pyridostigmine for < 6 weeks duration (must be greater than 6 weeks to be included in TAM4MTM).
6. 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).
7. Subject has a contraindication to tamoxifen or its ingredients

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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6 participants in 2 patient groups, including a placebo group

Drug: ApoTamox 10mg

Experimental group

Description:

Drug: Tamoxifen (tamoxifen citrate); ApoTamox 10 mg tablets orally twice daily for 6 months

Treatment:

Drug: ApoTamox 10mg

Placebo

Placebo Comparator group

Description:

Placebo (no active ingredients) tablets orally twice daily for 6 months

Treatment:

Drug: Placebo