Phase-II randomized clinical trial to evaluate the effect of Loratadine associated with Rapamune on Lymphagioleiomyomatosis (LAM).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

18 Aug 2022 → 29 Nov 2024

Decision date (initial)

2024-09-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516808-42-00

EudraCT number

2020-000702-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

Evaluate the safety profile of loratadine in combination with rapamycin after 48 weeks Assess security (incidence of adverse events according to their intensity,severity, relation to treatment) of the combination of loratadine and rapamycin compared with rapamycin in monotherapy in patients with LAM.

Secondary objectives 3

1. - Quality of life and progression free-survival time.
2. -Changes in the established LAM serum biomarker VEGFD.
3. -The utility of the major histamine-derived metabolite methylimidazoleacetic acid (MIAA) for monitoring disease progression and biological treatment effect.

Conditions and MedDRA coding

Effect of loratadine in patients with lymphangioleiomyomatosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. -Patients affected by LAM, over 18 years of age, who present: - Definitive diagnosis of LAM based on international consensus and clinical guidelines, maximum 10 years before randomization. The diagnosis must be certain (after evaluation by the Multidisciplinary Interstice Committee of each participating center).
2. --FEV1 > 35% and DLCO > 20%
3. -Oxygen saturation (SatO2) > 85% at rest and without supplemental oxygen
4. -Chest CT 12 months before randomization suggestive of LAM
5. -Taking stable doses of rapamycin for at least the last 3 months

Exclusion criteria 14

1. - Habitual concomitant use (minimum 3 days/week) of any histamine antagonist (including in addition to loratadine, ebastine, and similar).
2. - Hypersensitivity to histamine antagonists or anti-histamines, especially the HR1 receptor.
3. - Pregnancy.
4. - Breastfeeding and desire to procreate in the year following inclusion.
5. - Inadequate contraceptive treatment. In the case of women of age fertile (between menarche and menopause) only those who follow contraceptive methods recommended by the Clinical Trial Facilitation Group (CTFG) will be included during treatment with the drug and during the 12 weeks following its interruption.
6. - Active smoking (at the time of study or taking last cigarette less than 3 months ago).
7. - Use of immunosuppressants or systemic immunomodulators or chemotherapy within 30 days of screening.
8. - Take oral corticosteroids at doses > 15 mg/day, vasodilator therapies for pulmonary arterial hypertension (for example, bosentan), unapproved or investigational drugs for LAM in the period of 4 weeks before the screening visit.
9. - Severe liver failure.
10. - Renal failure: Creatinine clearance (CrCl) <60 ml/min
11. - Patients who receive as treatment some powerful inhibitor or CYP liver enzyme inducer during screening or 14 days prior to randomization: antifungals (e.g. ketoconazole, itraconazole), clarithromycin, telithromycin, cobicistate, phenytoin, carbamazepine, barbiturates, rifampicin, protease inhibitors such as atazanavir, ritonavir and saquinavir, or good grapefruit intake.
12. - Allergic asthma or other major allergic disorder that requires daily or habitual taking of anti-histamines.
13. - Other coexisting serious lung disease (in researcher's opinion) such as severe emphysema, bronchiectasis, asthma, severe uncontrolled SAHS.
14. -Use of attenuated vaccines while taking Rapamune (according to the technical data sheet of this drug), and patients with lactose intolerance (according to the technical data sheet of loratadine).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of adverse effects associated with taking loratadine associated with rapamycin, including nausea, diarrhea, abdominal pain, vomiting, headache, hypertransaminasemia.

Secondary endpoints 4

1. - Maintenance of clinical stability (FEV1 drop < 10% or DLCO < 15%)
2. - Decrease in the number of hospitalizations for any cause and respiratory causes
3. - Lung transplant
4. - Death.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Sponsor organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Address

Avinguda De La Gran Via De L'hospitalet 199

City

L'Hospitalet De Llobregat

Postcode

08908

Country

Spain

Scientific contact point

Organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Contact name

María Molina

Public contact point

Organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Contact name

María Molina

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications