LAM (laymans term) and Lymphangioleiomatosis
Conditions
Interventions
Capsules of LAM-001 will contain 100 *g (up to a maximum of 200 *g) of
rapamycin formulated in hydroxypropyl methyl cellulose dry-powder capsules,
using lactose as the excipient.
Sponsors
AI Therapeutics
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. The patient is independently capable of providing informed consent and provides signed informed consent, witnessed by clinic staff, before any study-related assessments or procedures are performed. 2. The patient is female and from 18 to 70 years of age, inclusive, with a body mass index from 18.0 to 32.0 kg/m2, inclusive, at the time of screening (Visit 1) a. Patients cannot be pregnant or lactating/breast feeding and must be surgically sterile, postmenopausal (no menses for the previous 12 months), or practicing a highly effective method of birth control as described in this protocol. Acceptable methods of birth control are: certain types of hormonal contraception (eg, birth control pill, injection, implant, transdermal patch, or vaginal ring. Progestin-based contraception is allowed. Only low dose estrogen-containing contraceptives are allowed [estrogen dose between 10 and 25 *g]), intrauterine device, tubal ligation (tied tubes), or a partner with a vasectomy. High dose estrogen containing contraceptives are not allowed in this study. Gonadotropin-releasing hormone agonist contraceptives are not allowed in this study. b. Patients must not be planning to become pregnant during the study and agree to use highly effective contraception for at least 90 days after the last dose of study drug. 3. The patient has a confirmed diagnosis of LAM as determined by prior clinical evaluation, including compatible chest CT AND one of the following: a. Biopsy (lung, abdominal mass, lymph node, or kidney) or cytology (from thoracic or abdominal sources that show HMB45 positive staining of spindles/epithelioid cells); OR b. Tuberous sclerosis, angiomyolipoma (diagnosed by prior high resolution chest CT, magnetic resonance imaging, ultrasonography, or biopsy); OR c. Chylous pleural effusion, as verified by thoracentesis (without other etiology); OR d. Serum VEGF-D level *800 pg/mL as part of the previous diagnostic evaluation. 4. The patient's pulmonary symptoms and lung function have been stable, as judged by the investigator, over the 3 months before Visit 1. 5. The patient has the ability to perform study procedures, including correct use of the RS01 DPI and the spirometry maneuvers. 6. The patient agrees to comply with all protocol requirements.
Exclusion criteria
Exclusion criteria: 1. The patient has a pre-bronchodilator FEV1 of *60% of predicted during the screening or baseline visits. 2. The patient has used mTOR inhibitors (e.g., rapamycin, everolimus) within 90 days before Visit 1. 3. The patient is considered likely to need oral rapamycin or another mTOR inhibitor within 6 months following Visit 1, in the opinion of the investigator. 4. The patient has had a pneumothorax within the 2 months before Visit 1. 5. The patient is a smoker. Patients will be defined as ex smokers and eligible for participation in the study if they have not consumed tobacco products or other forms of nicotine replacement therapy for at least 6 months before Visit 1. 6. The patient has a concurrent significant respiratory disease, including any of the following: a. Confirmed or suspected smoking-related chronic obstructive pulmonary disease. b. Other significant respiratory disorder including, but not limited to, pulmonary hypertension, cor pulmonale, pulmonary fibrosis, or bronchiectasis. c. Previous lung transplantation or is active on a transplant list. 7. The patient requires regular use of inhaled corticosteroids. 8. The patient has significant or uncontrolled disease of any organ system, including psychological illness, that is likely to interfere with the study conduct, patient safety, or the interpretation of study evaluations, as determined by the investigator, including but not limited to the following: a. Unstable angina, myocardial infarction, previous history of pericarditis, or cerebrovascular event within the past 12 months before screening or uncontrolled hypertension or arrhythmia. b. Uncontrolled dyslipidemia. c. Poorly controlled diabetes mellitus, as evidenced by hemoglobin A1c >8.5%. d. Known history of human immunodeficiency virus or chronic viral hepatitis infection e. Diagnosed with active or untreated latent tuberculous infection or active pulmonary nontuberculous mycobacterial infection. A tuberculosis screening test is not required. Patients who completed a course of antituberculous therapy at least 1 year before screening with no clinical or radiological evidence of disease recurrence may be eligible for screening. f. History of malignancy or treatment for malignancy in the 2 years before screening. Patients who have received curative treatment with resection of nonmelanoma skin cancer or with in situ carcinoma of the cervix may be eligible. 9. The patient has a known allergy to rapamycin or has previously discontinued rapamycin due to pulmonary or other safety concerns. 10. The patient has a history of severe milk protein allergy (patients with lactose intolerance are eligible). 11. The patient requires supplemental oxygen therapy as either longterm oxygen therapy or as required ambulatory oxygen. 12. The patient has a significantly abnormal laboratory result at Visit 1, including any of the following: a. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 × upper limit of normal (ULN) b. Hemoglobin 1.5 mg/dL 13. The patient has significantly abnormal ECG results at Visit 1. The investigator will use clinical jud
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Exploratory Biomarker Endpoints The endpoints for VEGF-D and other biomarkers are absolute concentration, changes over time, and variability. Efficacy Endpoints Not applicable. Safety Endpoints * AE monitoring and recording * Clinical laboratory results (hematology, serum chemistry, and urinalysis) * PFTs * 6MWT * Vital sign measurements (systolic and diastolic blood pressures, heart rate, respiratory rate, and body temperature) * Resting pulse oximetry * 12-lead ECG results * Physical examination findings | — |
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic Endpoints The following are the primary rapamycin PK endpoints: * Cmax: Period 1, Days 1 and 14; Period 2, Day 84 * AUC0-24: Period 1, Days 1 and 14; Period 2, Day 84 * AUC0-t: Period 1, Days 1 and 14; Period 2, Day 84 | — |
Countries
Netherlands
Outcome results
None listed