Rapamycin Treatment for Activated Phosphoinositide 3-Kinase δ Syndrome

NCT03383380 | Completed Phase 1 DMC

• 1 other identifier: RTAPDS
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this proposed research is to evaluate the efficacy and safety of the rapamycin therapy in patients with activated phosphoinositide 3-kinase δ syndrome (APDS).

Conditions

Activated PI3K-delta Syndrome; Immunodeficiency Primary

Keywords

Activated PI3K-delta Syndrome; Immunodeficiency Primary; Akt/mTOR pathway; Rapamycin Therapy; Hyperphosphorylation

Outcome Measures

Primary Outcomes (3)

• Frequency of Recurrent Infections

  Frequency of recurrent infections of the patients as indicators of rapamycin efficacy.

  5 years

• Hepatosplenomegaly

  Changes in hepatosplenomegaly with rapamycin treatment.

  5 years

• Lymphocyte subset

  The changes of lymphocytes subset were evaluated by flow cytometry.

  5 years

Secondary Outcomes (1)

• Incidence of Adverse Events

  5 years

Study Arms (1)

Rapamycin

EXPERIMENTAL

Treatment for patients with activated phosphoinositide 3-kinase δ syndrome

Drug: Rapamycin

Interventions

Rapamycin DRUG

Gain-of-function (GOF) PIK3CD mutations lead to PI3Kδ hyperactivity, with the downstream mediators Akt and mTOR hyperphosphorylated. The mammalian/mechanistic target of rapamycin inhibitor rapamycin may be effective to control the progress of this disease.

Also known as: Sirolimus

Rapamycin

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with activated phosphoinositide 3-kinase δ syndrome
• No more than 18 years old

You may not qualify if:

• Patients with serious fungous infection
• Patients with serious complications
• Lack of parental consent

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead

Study Sites (2)

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, China

Location

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Location

Related Publications (6)

• Coulter TI, Chandra A, Bacon CM, Babar J, Curtis J, Screaton N, Goodlad JR, Farmer G, Steele CL, Leahy TR, Doffinger R, Baxendale H, Bernatoniene J, Edgar JD, Longhurst HJ, Ehl S, Speckmann C, Grimbacher B, Sediva A, Milota T, Faust SN, Williams AP, Hayman G, Kucuk ZY, Hague R, French P, Brooker R, Forsyth P, Herriot R, Cancrini C, Palma P, Ariganello P, Conlon N, Feighery C, Gavin PJ, Jones A, Imai K, Ibrahim MA, Markelj G, Abinun M, Rieux-Laucat F, Latour S, Pellier I, Fischer A, Touzot F, Casanova JL, Durandy A, Burns SO, Savic S, Kumararatne DS, Moshous D, Kracker S, Vanhaesebroeck B, Okkenhaug K, Picard C, Nejentsev S, Condliffe AM, Cant AJ. Clinical spectrum and features of activated phosphoinositide 3-kinase delta syndrome: A large patient cohort study. J Allergy Clin Immunol. 2017 Feb;139(2):597-606.e4. doi: 10.1016/j.jaci.2016.06.021. Epub 2016 Jul 16.

  PMID: 27555459 BACKGROUND

• Lucas CL, Kuehn HS, Zhao F, Niemela JE, Deenick EK, Palendira U, Avery DT, Moens L, Cannons JL, Biancalana M, Stoddard J, Ouyang W, Frucht DM, Rao VK, Atkinson TP, Agharahimi A, Hussey AA, Folio LR, Olivier KN, Fleisher TA, Pittaluga S, Holland SM, Cohen JI, Oliveira JB, Tangye SG, Schwartzberg PL, Lenardo MJ, Uzel G. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110delta result in T cell senescence and human immunodeficiency. Nat Immunol. 2014 Jan;15(1):88-97. doi: 10.1038/ni.2771. Epub 2013 Oct 28.

  PMID: 24165795 BACKGROUND

• Tsujita Y, Mitsui-Sekinaka K, Imai K, Yeh TW, Mitsuiki N, Asano T, Ohnishi H, Kato Z, Sekinaka Y, Zaha K, Kato T, Okano T, Takashima T, Kobayashi K, Kimura M, Kunitsu T, Maruo Y, Kanegane H, Takagi M, Yoshida K, Okuno Y, Muramatsu H, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Kojima S, Ogawa S, Ohara O, Okada S, Kobayashi M, Morio T, Nonoyama S. Phosphatase and tensin homolog (PTEN) mutation can cause activated phosphatidylinositol 3-kinase delta syndrome-like immunodeficiency. J Allergy Clin Immunol. 2016 Dec;138(6):1672-1680.e10. doi: 10.1016/j.jaci.2016.03.055. Epub 2016 Jul 14.

  PMID: 27426521 BACKGROUND

• Vignesh P, Rawat A, Singh S. An Update on the Use of Immunomodulators in Primary Immunodeficiencies. Clin Rev Allergy Immunol. 2017 Apr;52(2):287-303. doi: 10.1007/s12016-016-8591-2.

  PMID: 27873163 BACKGROUND

• Angulo I, Vadas O, Garcon F, Banham-Hall E, Plagnol V, Leahy TR, Baxendale H, Coulter T, Curtis J, Wu C, Blake-Palmer K, Perisic O, Smyth D, Maes M, Fiddler C, Juss J, Cilliers D, Markelj G, Chandra A, Farmer G, Kielkowska A, Clark J, Kracker S, Debre M, Picard C, Pellier I, Jabado N, Morris JA, Barcenas-Morales G, Fischer A, Stephens L, Hawkins P, Barrett JC, Abinun M, Clatworthy M, Durandy A, Doffinger R, Chilvers ER, Cant AJ, Kumararatne D, Okkenhaug K, Williams RL, Condliffe A, Nejentsev S. Phosphoinositide 3-kinase delta gene mutation predisposes to respiratory infection and airway damage. Science. 2013 Nov 15;342(6160):866-71. doi: 10.1126/science.1243292. Epub 2013 Oct 17.

  PMID: 24136356 BACKGROUND

• Walsh CM, Fruman DA. Too much of a good thing: immunodeficiency due to hyperactive PI3K signaling. J Clin Invest. 2014 Sep;124(9):3688-90. doi: 10.1172/JCI77198. Epub 2014 Aug 18.

  PMID: 25133419 BACKGROUND

MeSH Terms

Conditions

Activated PI3K-delta Syndrome; Primary Immunodeficiency Diseases

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Jinqiao Sun, Ph.D.,M.D

  Children's Hospital of Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 12, 2017
• First Posted: December 26, 2017
• Study Start: December 1, 2017
• Primary Completion: November 30, 2022
• Study Completion: November 30, 2023
• Last Updated: July 9, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)