Rapamycine vs Placebo for the Treatment of Inclusion Body Myositis (RAPAMI)

Étude de l'Effet de la Rapamycine Sur la Force Musculaire et la réponse Immunitaire au Cours de la Myosite à Inclusions: étude RAPAMI"

Sporadic Inclusion Body Myositis (IBM) is the most frequent inflammatory myopathy in patients over 50. It is a slowly progressive, but today untreatable (notably by classical immunosuppressants) disease.

Rapamycin used in organ transplantation blocks the activity of T effector cells, preserves T regulatory cells and induces autophagy (protein degradation), all parameters impaired during IBM.

RAPAMI is a prospective, randomised, controlled, double blind, monocentric, phase IIb trial evaluating rapamycine against placebo.

Study Overview

• Status: Completed
• Conditions: Inclusion Body Myositis (IBM)
• Intervention / Treatment: Drug: Rapamycin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75651
    • CIC Paris Est _Hôpital Pitié Salpêtrière

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• IBM defined by the Benveniste & Hilton-Jones ( Neuromuscul Disord. 2010;20: 414-21) or Llyod criteria (Neurology 2014; 83: 426-433)

Exclusion Criteria:

• Impossiblility to walk 10 meters
• Hypersensitivity to rapamycin or one compound of the oral solution
• Severe respiratory insufficiency (FVC < 50% and/or FEV1 < 50%)
• Severe chronic kidney disease (Estimated Glomerular Filtration Rate < 15 ml/min and/or proteinuria > 0.3 g/24h)
• Chronic liver disease (cirrhosis and/or ALT/AST > 2.5 normal values)
• Cancer non in remission (necessitating specific treatment) during the past 12 months
• Connective Tissue Disease non in remission (necessitating specific treatment) during the past 12 months
• Pregnancy
• Seropositivity for HIV, HCV or HBV
• Total cholesterolemia > 8 mmol/l
• Triglyceridemia > 5 mmol/l
• Hemoglobinemia < 11 g/dL
• Thrombopenia < 100 000/mm3
• Neutropenia < 1500/ mm3
• Lymphopenia < 1000/ mm3

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rapamycin; rapamycin 1 mg/ml oral solution, 2 mg/day (2 ml/day), once a day, during one year	Drug: Rapamycin; Experimental: rapamycin oral solution, 2 mg/day during one year Comparator: placebo; Other Names: Sirolimus; Rapamune
Placebo Comparator: Placebo; Placebo oral solution, 2 ml/day, once a day, during one year	Drug: Placebo; Comparator: placebo; Other Names: Phosal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
stabilization of quadiceps strength measured by myometry	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
stabilization of hand grip strength measured by myometry		52 weeks
comparison of 6 minutes walking test		52 weeks
composite measure of the handicap	Rivermead Mobility Index (RMI), scale Walton, Inclusion Body Myositis Weakness Composite Index (IBMWCI), Inclusion Body Myositis Functional rating scale (IBMFRS)	52 weeks
Quality of life by different scales	Health Assessment Questionnaire (HAQ), Instrumental activities of daily living (IADL),Individualized Neuromuscular Quality of Life Questionnaire (INQol)	52 weeks
measures of muscle fatty replacement by MRI		52 weeks
Measure of the tolerance	Efficacy will be measured by: check list of the known side effect of rapamycin.	52 weeks
measure of inflammation by MRI		52 weeks

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France

Publications and helpful links

General Publications

• Benveniste O, Hilton-Jones D. International Workshop on Inclusion Body Myositis held at the Institute of Myology, Paris, on 29 May 2009. Neuromuscul Disord. 2010 Jun;20(6):414-21. doi: 10.1016/j.nmd.2010.03.014. Epub 2010 Apr 21. No abstract available.
• Lloyd TE, Mammen AL, Amato AA, Weiss MD, Needham M, Greenberg SA. Evaluation and construction of diagnostic criteria for inclusion body myositis. Neurology. 2014 Jul 29;83(5):426-33. doi: 10.1212/WNL.0000000000000642. Epub 2014 Jun 27.
• Benveniste O, Hogrel JY, Belin L, Annoussamy M, Bachasson D, Rigolet A, Laforet P, Dzangue-Tchoupou G, Salem JE, Nguyen LS, Stojkovic T, Zahr N, Hervier B, Landon-Cardinal O, Behin A, Guilloux E, Reyngoudt H, Amelin D, Uruha A, Mariampillai K, Marty B, Eymard B, Hulot JS, Greenberg SA, Carlier PG, Allenbach Y. Sirolimus for treatment of patients with inclusion body myositis: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2b trial. Lancet Rheumatol. 2021 Jan;3(1):e40-e48. doi: 10.1016/S2665-9913(20)30280-0. Epub 2020 Oct 12.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2015
• Primary Completion (Actual): January 22, 2018
• Study Completion (Actual): January 22, 2018

Study Registration Dates

• First Submitted: May 13, 2015
• First Submitted That Met QC Criteria: June 23, 2015
• First Posted (Estimated): June 25, 2015

Study Record Updates

• Last Update Posted (Estimated): September 2, 2025
• Last Update Submitted That Met QC Criteria: August 25, 2025
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Myositis; Myositis, Inclusion Body; Organic Chemicals; Substandard Drugs; Pharmaceutical Preparations; Macrolides; Lactones; Sirolimus; Counterfeit Drugs
• Other Study ID Numbers: C12-66; 2013-003485-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO