A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of LAM-001 in Patients with Lymphangioleiomyomatosis
- Conditions
- LAM (laymans term) and Lymphangioleiomatosis10006436
- Registration Number
- NL-OMON48177
- Lead Sponsor
- AI Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
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.
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 <100 kg/m3
c. Platelets <120,000/mm3
d. Absolute neutrophil count <1,500/mm3
e. Total white blood cell count <4,000/mm3
f. Serum creatinine >1.5 mg/dL
13. The patient has significantly abnormal ECG results at Visit 1. The
investigator will use clinical jud
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Pharmacokinetic Endpoints<br /><br>The following are the primary rapamycin PK endpoints:<br /><br>* Cmax: Period 1, Days 1 and 14; Period 2, Day 84<br /><br>* AUC0-24: Period 1, Days 1 and 14; Period 2, Day 84<br /><br>* AUC0-t: Period 1, Days 1 and 14; Period 2, Day 84</p><br>
- Secondary Outcome Measures
Name Time Method <p>Exploratory Biomarker Endpoints<br /><br>The endpoints for VEGF-D and other biomarkers are absolute concentration,<br /><br>changes over time, and variability.<br /><br><br /><br>Efficacy Endpoints<br /><br>Not applicable.<br /><br><br /><br>Safety Endpoints<br /><br>* AE monitoring and recording<br /><br>* Clinical laboratory results (hematology, serum chemistry, and urinalysis)<br /><br>* PFTs<br /><br>* 6MWT<br /><br>* Vital sign measurements (systolic and diastolic blood pressures, heart rate,<br /><br>respiratory rate, and body temperature)<br /><br>* Resting pulse oximetry<br /><br>* 12-lead ECG results<br /><br>* Physical examination findings</p><br>