Study evaluating the treatment with colchicine for the amyotrophic lateral sclerosis

• Register: EUCTR
• Last refreshed on: 12 November 2018
• Main ID: EUCTR2017-004459-21-IT
• Date of registration: 07/11/2018
• Prospective Registration: No
• Primary sponsor: AZIENDA OSPEDALIERO-UNIVERSITARIA POLICLINICO DI MODENA
• Public title: Study evaluating the treatment with colchicine for the amyotrophic lateral sclerosis
• Scientific title: Colchicine for Amyotrophic Lateral Sclerosis: a phase II, randomized, double blind, placebo controlled, multicenter clinical trial - Co-ALS
• Date of first enrolment: 11/09/2018
• Target sample size: 54
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004459-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Italy

Contacts

• Name: Centro coordinatore
• Affiliation: Ospedale Civile S. Agostino Estense

• Name: Centro coordinatore
• Affiliation: Ospedale Civile S. Agostino Estense

Key inclusion & exclusion criteria

Inclusion criteria:
- Patients diagnosed with a laboratory supported , clinically “probable” or “definite” amyotrophic lateral sclerosis according to the Revised El Escorial criteria (Brooks, 2000)
- Sporadic ALS
- ALS phenotypes: classic or bulbar
- Female or male patients aged between 18 and 80 years old
- Disease duration from symptoms onset no longer than 18 months at the screening visit
- Patients treated with a stable dose of Riluzole (100 mg/day) for at least 30 days prior to screening
- Patients with a weight > 50 kg and a BMI =18
- Patients with a FVC (Forced Vital Capacity) equal or more than 65 % predicted normal value for gender, height, and age at the screening visit
- Patients able and willing to comply with study procedures as per protocol
- Patients able to understand, and capable of providing informed consent at screening visit prior to any protocol-specific procedures
- Use of highly effective contraception both for males and females
Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 29
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion criteria:
- Prior use of colchicine
- Prior allergy/sensitivity to colchicine
- Receiving colchicine or other anti-inflammatory drugs (such as corticosteroids, methotrexate, anti-neoplastic, Interleukin 1-1b antagonist, Tumor necrosis factor-alpha inhibitor)
- Receiving food or co-medications such as strong-moderate cytochrome P450 3A4 inhibitors that will result in elevated plasma level of colchicine
- Inflammatory disorders (SLE, Rheumatoid arthritis, connective tissue disorder) or chronic infections (HIV, hepatitis B or C infection) or significant history of malignancy
- Severe renal (eGFR< 30ml/min/1.73m2), or liver failure or liver aminotransferase (ALT/AST > 2x Upper limit of normal)
- Existing blood dyscrasia (e.g., myelodysplasia)
- White blood cells<4,000/mm³, platelets count<100,000/mm³, hematocrit<30%
- Severe comorbidities (heart, renal, liver failure), autoimmune diseases or any type of interstitial lung disease
- Patients who underwent non invasive ventilation, tracheotomy and /or gastrostomy
- Women who are pregnant or breastfeeding
- Participation in pharmacological studies within the last 30 days before screening
- Patients with known pathogenic mutations (SOD1, TARDBP, FUS, C9ORF72)
- Patients with familial ALS defined as presence of at least one first degree family member (parents/son/daughter/brother/sister) affected by ALS
- Patients with the following ALS phenotypes: flail arm, flail leg, UMN-p, respiratory, PLS, progressive muscular atrophy



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Definite or probable amyotrophic lateral sclerosis
MedDRA version: 20.0 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: LLT Classification code 10052889 Term: ALS System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: COLCHICINA LIRCA - 1 MG COMPRESSE 60 COMPRESSE
Product Name: Colchicina
Product Code: Colchicina
Pharmaceutical Form: Tablet
INN or Proposed INN: COLCHICINA
CAS Number: 64-86-8
Current Sponsor code: Colchicina
Other descriptive name: COLCHICINA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)

Primary end point(s): Proportion of patients exhibiting a positive response (considered as a decrease in ALS progression) comparing baseline and treatment end (week 30) between colchicine and placebo arm, using ALS Functional Rating Scale—Revised (ALSFRS-R)

Main Objective: The primary objective is to assess whether different colchicine doses decrease disease progression, measured through ALSFRS-R (ALS Functional Rating Scale-Revised), in ALS patients compared to the control arm.

Secondary Objective: - To evaluate colchicin safety and tolerability in ALS patients;
- To analyse colchicine efficacy in enhancing autophagy quantifying mRNA and protein levels of p62, LC3, TFEB, ATGs, HSPB8, BAG3, BAG1, HSP70, and HSF1, also in muscle biopsy of patients (optional);
- To identify changes in stress granules response and composition;
- Measure of the overall levels and the relative ratio between soluble and insoluble species of TDP-43, TDP-43 fragments, SQSTM1/p62, UBQLN, OPTN in fibroblasts and lymphoblasts;
- To study colchicine effects on extracellular vesicles secretion of TDP-43, hyperphosphorylated TDP-43, SQSTM1/p62, UBQLN and OPTN;
- To study colchicine effects on peripheral and CSF biomarkers: creatinine, albumin, CK, and vitamin D, phosphorylated neurofilaments heavy chain, IL18 and its endogenous inhibitor IL-18BP, MCP1 and IL17;
- To evaluate colchicine efficacy in terms of survival and forced vital capacity (FVC) progression

Timepoint(s) of evaluation of this end point: The primary endpoint will be assessed after 30 weeks from the start of treatment with colchicine or placebo

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The endpoint will be evaluated at weeks 8, 30 and 54 after the start of treatment with colchicine or placebo

Secondary end point(s): Absolute and relative change from baseline of the score of ALSAQ-40 (Amyotrophic Lateral Sclerosis Specific Assessment Questionnnaire) at weeks 8, 30 and 54

Secondary ID(s)

Co-ALS