NCT02147886

A Single-Center, Randomized, Double-Blind, Parallel-Group, Dose-Controlled Study, to Assess Safety, Tolerability and Efficacy of Intravenous Cabaletta® in Patients With Machado-Joseph Disease

Completed Phase 2 Last updated 21 November 2016

What this trial tests

Phase 2 trial testing Cabaletta for IV infusion once weekly during 24 weeks in Machado-Joseph Disease / Spinocerebellar Ataxia 3 in 15 participants. Completed in 1 November 2016.

Timeline

1 July 2014

Primary endpoint
1 October 2016

1 November 2016

Quick facts

Lead sponsor	Bioblast Pharma Ltd.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	15
Start date	1 July 2014
Primary completion	1 October 2016
Estimated completion	1 November 2016
Sites	1 location across Israel

Drugs / interventions tested

• Cabaletta for IV infusion once weekly during 24 weeks — full drug profile →
• Cabaletta for IV infusion once weekly during 24 weeks — full drug profile →

Conditions studied

• Machado-Joseph Disease / Spinocerebellar Ataxia 3 — all drugs for Machado-Joseph Disease / Spinocerebellar Ataxia 3 →

Sponsor

Bioblast Pharma Ltd. — full company profile →

Who can join

Adults 18 to 75, any sex, with Machado-Joseph Disease / Spinocerebellar Ataxia 3. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Adverse events
  Time frame: 28 weeks
  Safety will be evaluated on the basis of the following assessments: Adverse events , physical examination, 12-lead ECG, vital signs, safety laboratory evaluations
• Physical examination
  Time frame: 28 weeks
  Safety will be evaluated on the basis of the following assessments: Adverse events , physical examination, 12-lead ECG, vital signs, safety laboratory evaluations
• Vital signs
  Time frame: 28weeks
  Safety will be evaluated on the basis of the following assessments: Adverse events , physical examination, 12-lead ECG, vital signs, safety laboratory evaluations
• 12-lead ECG
  Time frame: 28weeks
  Safety will be evaluated on the basis of the following assessments: Adverse events , physical examination, 12-lead ECG, vital signs, safety laboratory evaluations
• Safety laboratory tests
  Time frame: 28weeks
  Safety will be evaluated on the basis of the following assessments: Adverse events , physical examination, 12-lead ECG, vital signs, safety laboratory evaluations

Sponsor's own description

* This is an exploratory, randomized, parallel-group, dose escalation and dose-controlled study without a placebo arm.
* Eligible patients will be randomized in a 1:1 ratio (double-blind) to receive Cabaletta in 2 doses, once weekly for 22 weeks (total of 24 weeks of treatment).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: a novel therapeutic lead to treat frontotemporal dementia.
   Holler CJ, Taylor G, McEachin ZT, Deng Q, et al · · 2016 · cited 88× · PMID 27341800 · DOI 10.1186/s13024-016-0114-3
2. From Pathogenesis to Novel Therapeutics for Spinocerebellar Ataxia Type 3: Evading Potholes on the Way to Translation.
   Da Silva JD, Teixeira-Castro A, Maciel P. · · 2019 · cited 53× · PMID 31691128 · DOI 10.1007/s13311-019-00798-1
3. AKT modulates the autophagy-lysosome pathway via TFEB.
   Palmieri M, Pal R, Sardiello M. · · 2017 · cited 43× · PMID 28636416 · DOI 10.1080/15384101.2017.1337968
4. Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado-Joseph Disease through Integration of Pathological Biomarkers and Therapeutic Strategies.
   Chen YS, Hong ZX, Lin SZ, Harn HJ. · · 2020 · cited 25× · PMID 32357546 · DOI 10.3390/ijms21093063
5. Trehalose restores functional autophagy suppressed by high glucose.
   Xu C, Chen X, Sheng WB, Yang P. · · 2019 · cited 24× · PMID 30769031 · DOI 10.1016/j.reprotox.2019.02.005
6. Current concepts in the treatment of hereditary ataxias.
   Braga Neto P, Pedroso JL, Kuo SH, Marcondes Junior CF, et al · · 2016 · cited 24× · PMID 27050855 · DOI 10.1590/0004-282x20160038
7. The increased activity of a transcription factor inhibits autophagy in diabetic embryopathy.
   Xu C, Chen X, Reece EA, Lu W, et al · · 2019 · cited 14× · PMID 30312583 · DOI 10.1016/j.ajog.2018.10.001
8. Small Molecules Inducing Autophagic Degradation of Expanded Polyglutamine Protein through Interaction with Both Mutant ATXN3 and LC3.
   Lin TH, Chen WL, Hsu SF, Chen IC, et al · · 2024 · cited 2× · PMID 39409036 · DOI 10.3390/ijms251910707