Effect of Loratadine in Lymphangioleiomyomatosis

NCT05190627 | Unknown Phase 2 DMC

• 1 other identifier: LORALAM
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 6

Brief Summary

INTRODUCTION: LAM is a rare and lethal disease characterized by progressive cystic lung destruction. Inhibition of mTOR with rapamycin is the current standard of care (SOC), which can slow-down disease. Plasma major histamine metabolite (Methylimidazoleacetic acid \[MIAA\]) is increased in LAM. Loratadine is a histamine receptor antagonist (HR1), which inhibits LAM cell proliferation. Therefore, a novel phase-II clinical trial for assessing safety and potential benefits of loratadine in LAM has been initiated. METHODS: LORALAM clinical trial, phase-II, double-blind, randomized, placebo controlled, parallel-group, multicentre study initiates recruitment in July 2020. Enrollment plan includes 62 subjects with LAM on treatment with rapamycin ≥3 months, randomized 1:1 to add oral loratadine 10mg/day or placebo, once daily, for 52 weeks. Recruitment will end in June 2021. The primary endpoints are 1) to assess the safety profile of loratadine associated with rapamycin, 2) lung function decline after 52 weeks of treatment. The secondary endpoints are a) quality of life and progression free-survival time, b) changes in the established LAM serum biomarker VEGFD, c) the utility of MIAA for monitoring disease progression and biological treatment effect. ETHICS AND DISSEMINATION: The study will be carried out in accordance with Good Clinical Practice guidelines, Declaration of Helsinki principles, and each ethical committee. This clinical trial contemplates the possibility of increasing the number of centers and including patients from patient support groups (LAM foundation, AELAM)

Conditions

Lymphangioleiomyomatosis

Keywords

LAM; Rapamycin; Loratadine

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events (safety) of loratadine in combination with sirolimus after 52 weeks of treatment

  To compare the incidence of adverse events in LAM patients treated with sirolimus and loratadine versus sirolimus alone. Any adverse event related to both drugs, including nausea, diarrhea, stomach discomfort, vomiting, headache and liver hipertransaminasemia, will be evaluated.

  52 weeks

Secondary Outcomes (6)

• To evaluate the effect of loratadine associated with sirolimus on quality of life measured by the Saint George's Questionnaire

  52 weeks

• Study-drug discontinuation

  52 weeks

• Serum levels of sirolimus

  52 weeks

• To evaluate the effect of loratadine associated with sirolimus on progression-free survival time

  52 weeks

• To evaluate the effect of loratadine associated with sirolimus on hospitalization rate

  52 weeks

Study Arms (2)

Loratadine treatment on rapamycin

EXPERIMENTAL

Loratadine (oral administration, daily dose 10mg) in LAM patients that are treated with rapamycin

Drug: Loratadine

Placebo treatment on rapamycin

PLACEBO COMPARATOR

Placebo (oral administration, daily dose 10 mg) in LAM patients that are treated with rapamycin

Drug: Placebo 10mg/day added to rapamycin for 12 months

Interventions

Loratadine DRUG

Loratadine 10mg/day added to rapamycin for 12 months

Also known as: Clarytine

Loratadine treatment on rapamycin

Placebo 10mg/day added to rapamycin for 12 months DRUG

Placebo in the same type of capsule than the experimental drug

Placebo treatment on rapamycin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Written informed consent consistent with GCP and local laws signed prior to entry into the study.
• \. Patients with LAM and \> 18 years-old with:
• FEV1 \> 35% and DLCO \> 20%
• Oxygen saturation (SpO2) \> 85% by pulse oximetry while breathing ambient air at rest
• Patients with a definite diagnosis consistent with LAM prior to screening based on International consensus criteria within 10 years prior to randomization
• HRCT within 12 months prior to randomization with central reading demonstrating a radiological pattern suggesting LAM and some other criteria for initiating sirolimus (symptoms, FEV1 decline or the presence of abdominal lynphangioleiomiomas).

You may not qualify if:

• Concomitant use of other HR1 antagonist
• Hypersensitivity to HR1 antagonists
• Current smoker or ex-smoker having quit smoking \< 4 months prior to firs screening visit - Use of systemic immunosuppressants or chemotherapy within 30 days of screening.
• Receiving oral corticosteroids\>15mg/day, vasodilator therapies for pulmonary hypertension (e.g., bosentan), unapproved and/or investigational therapies for LAM or administration of such therapies within 4 weeks of initial screening.
• At baseline/screening visit, values of liver transaminases above 3 times upper limit, alkaline phosphatase above 2.5 times upper limit, or bilirubin above 1.5 times upper limit
• Creatinine clearance (CrCl)\<60ml/min (determined by Cockcroft-Gault Equation) at baseline/ screening visit.
• Patients treated with strong inhibitors and inducers of CYP either during the study or 14 days prior to enrolment in the study: antifungals (e.g., ketoconazole, itraconazole), clarithromycin, telithromycin, cobicistat, protease inhibitors (e.g., atazanavir, ritonavir, and saquinavir) and grapefruit juice, phenytoin, carbamazepine, barbiturates, rifampin.
• Current allergic asthma or other major allergic diseases that requires different daily anti- histaminic treatment.
• History of coexistent and clinically significant (in the opinion of the Investigator) chronic obstructive pulmonary disease (COPD), bronchiectasis, asthma, inadequately treated sleep- disordered breathing, or any clinically significant pulmonary diseases other than LAM.

Sponsors & Collaborators

• Institut d'Investigació Biomèdica de Bellvitge: lead

Study Sites (6)

University Hospital of Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

RECRUITING

Hospital Vall d'Hebron

Barcelona, Spain

NOT YET RECRUITING

Hospital La Princes

Madrid, Spain

ACTIVE NOT RECRUITING

Hospital Puerta de Hierro

Madrid, Spain

ACTIVE NOT RECRUITING

Hospital Marqués de Valdecillas

Santander, Spain

NOT YET RECRUITING

Hospital Virgen del Rocío

Seville, Spain

NOT YET RECRUITING

Related Links

• IDIBELL webpage

MeSH Terms

Conditions

Lymphangioleiomyomatosis

Interventions

Loratadine

Condition Hierarchy (Ancestors)

Lymphangiomyoma; Neoplasm, Lymphatic Tissue; Neoplasms by Histologic Type; Neoplasms; Perivascular Epithelioid Cell Neoplasms; Neoplasms, Connective and Soft Tissue; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyproheptadine; Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Study Officials

• Maria Molina-Molina, MD, PhD

  Institut d'Investigació Biomèdica de Bellvitge

  STUDY DIRECTOR

Central Study Contacts

Mar Chicote, PM

CONTACT

0034932607689; ufip@bellvitgehospital.cat

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Interstitial Lung Diseases Unit, Respiratory Department. Associated Professor (University of Barcelona)

Study Record Dates

• First Submitted: December 11, 2021
• First Posted: January 13, 2022
• Study Start: November 1, 2021
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2023
• Last Updated: January 27, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (6)