Background: The ATTeST study (NCT02770807), conducted in 22 centers on five continents, was a randomized, double-blind, placebo-controlled phase 3 clinical trial of safety and efficacy of two dose levels of intra-erythrocyte dexamethasone sodium phosphate (EryDex) compared to placebo, on neurological symptoms of children with ataxia-telangiectasia (A-T).Methods: The primary efficacy endpoint was change in neurological symptoms from baseline to month 6, measured by modified International Cooperative Ataxia Rating Scale (mICARS) and compared between EryDex and the placebo control using a mixed model repeated measures (MMRM) analysis. The point estimate of treatment effect (least square mean [LSM]) and a p-value are presented.Results: Between March 2nd, 2017 and May 13th, 2021, 175 participants were randomized and received at least one dose of drug: 59 low dose (LD), 57 high dose (HD), and 59 placebo, comprising the intention to treat (ITT) population. Modified ITT (mITT) population comprised 164 participants who received ≥1 dose of drug and had ≥1 efficacy assessments. Per protocol (PP) population comprised 107 participants who missed ≤1 dose of treatment. In the mITT population, mICARS LSM scores were -1·37 (p=0·0847) and -1·40 (p=0·0765), and in PP population LSM scores were -2·80 (p=0·0037) and -2·21 (p=0·0193) for LD and HD group, compared to placebo. For 6 to 9-year-olds in mITT population, LSM scores were -1·35 (p=0·2392) and -2·79 (p=0·0185) for LD and HD; and in PP population, LSM scores were -3·59 (p=0·0071) and -4·39 (p=0·0016) for LD and HD group, compared to placebo. Safety data are presented descriptively.Conclusions: At 6-month follow-up HD EryDex was effective in reducing mICARS scores in 6 to 9-year-olds. Both LD and HD EryDex were effective when used without skipping treatments and as outlined in the protocol. There were no safety concerns identified. Further studies of HD EryDex in the 6 to 9-year group are under way.Trial Registration: NCT02770807.Funding: EryDel S.p.A., Quince Therapeutics.Declaration of Interest: Declares “none” for interests: A.V., B.P., M.R., R.B., S.I.P., S.G., S.W., S.P., V.L., D.T., A.H., A.N. declares being a part of consortium which obtained Horizon 2020 grant for this project. A.S-P. declares funds, equipment and drug from EryDel received for this trial; grants for research in A-T (AT children’s project, AEFAT, Action for AT, Klinbeforsk, and Dam Foundation); and being the President of Norwegian Society for Medical Genetics. E.F. declares receiving support from EryDel for this project. G.J. declares being employed as a Chief Medical Officer by the study sponsor; he was medical monitor for this trial, and received stock options. I.M. declares receiving consulting fees/honoraria/travel support from Boehringer-Ingelheim, Takeda and CSL-Behring, for work unrelated to this project. She declares holding unpaid leadership positions in the past (president for ESID Society, MAB IPOPI). K.V. declares getting honoraria from MedLink Neurology and holding leadership positions (Secretary General, Indian Epilepsy Society and Asian Epilepsy Academy). L.B. declares holding a leadership role in Newron Pharmaceuticals and receiving stock options from Quince Therapeutics. MK.K. declares funding to her institution from EryDel for this trial; receiving funding from Quince Therapeutics for expanded access program; and getting travel support for the investigator meeting. M.M. declares receiving a grant/contract and travel support from EryDel; leadership position with Diatheva SrL; and holding EryDel and Quince Therapeutics stocks. P.P. declares EryDel’s research support for this trial, paid to his institution; research grants from ICMR, DST, SERB, DBT, Welcome-DBP, PACE, SKAN and MJF all paid to his institution; honoraria as faculty/speaker/author or travel/meeting registration support from the International Parkinson and Movement Disorder Society, Movement Disorders Societies of Korea, Taiwan and Bangladesh, and National Institute of Mental Health and Neurosciences; leadership positions include Chair of Education Committee of IPMDS, and unpaid Editor-in-Chief of Annals of Movement Disorders. R.Y. declares research grants from Indian Council of Medical Research (ICMR), Parkinson’s and Movement Disorders Research Fund of NIMHANS, SKAN foundation; book royalties from Jaypee Publisher; speaker honoraria from International Parkison’s and Movement Disorders Society; and leadership role in Parkinson’s Society of Karnataka. R.G. declares participation in data safety monitoring or advisory boards of: Biogen, Hikma, Merck, Roche, and Sanofi. T.C. declares consulting fees from Syneos Health Communications and Scholar Rock; honoraria for CME educational program development/review from MedForce and Muscular Dystrophy Association; and participation on safety monitoring or advisory boards for Taysha Giant Axonal Neuropathy. W.W. declares research funding from EryDel to the institution for this trial; being a member of a data safety monitoring board for clinical trial of an IMP in A-T; and being trustee of charity STARS. H.L. declares research funding and equipment from EryDel to the institution for this trial; consulting fees from EryDel for analysis of adverse events and presentation to the FDA, travel support for attending investigator meetings for this trial. V.U. declares research funding from EryDel to his institution for this trial. S.Z. declares that the Frankfurt University was funded by the Horizon grant of the EU and EryDel for conducting this trial; research grants outside submitted work (Palas GmbH Company Karlsruhe Germany “Aerosol measurement” and a grant from Ministry of Health of the German Republic (BMBF) for the study of Tiotropium in asthma 1-5 years); consulting fees or honoraria from Engelhard GmbH, Bӧhringer Ingelheim, Allergy Therapeutics, AstraZeneca, Sanofi Aventis, EryDel SpA, and Lofarma; member of EAACI Guidelines group on allergic asthma. M.K. declares funding from EryDel for this trial and funding from Quince Therapeutics for the expanded access program; consulting fees from Desitin Pharma, Eisai Pharma, STADApharm, and Life Science Consulting; travel support from Desitin Pharma; participation on a data safety monitoring board for Eisai Pharma; being on the Board and being a Vice President for Neuropaediatric Society (Germany, Austria, Switzerland).Ethical Approval: The trial was conducted in accordance with the Good Clinical Practice guidelines of the International Conference on Harmonization (ICH) and the ethical principles of the Declaration of Helsinki. Written informed consent/parental permission was obtained from all participants and/or parents or legal guardians, before screening. An independent data and safety monitoring board reviewed the safety data throughout the trial. The protocol, approved by regulatory authorities and ethics committees of all participating study sites.