Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of ANX005 in Adults With Amyotrophic Lateral Sclerosis (ALS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04569435
Recruitment Status : Not yet recruiting
First Posted : September 29, 2020
Last Update Posted : October 20, 2020
Sponsor:
Collaborator:
Worldwide Clinical Trials
Information provided by (Responsible Party):
Annexon, Inc.

Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of Intravenous ANX005 in Subjects with Amyotrophic Lateral Sclerosis (ALS).

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: ANX005 Phase 2

Detailed Description:

In this Phase 2a, multi-center, open label, proof-of-biology study of ANX005 will be administered to up to approximately 24 subjects with Amyotrophic Lateral Sclerosis (ALS) for up to 12 weeks.

Induction Dose: Each subject will receive induction dosing of ANX005 on Days 1 and 5 or 6 (5/6).

Maintenance Dose: Each subject will receive a maintenance dose of ANX005 every 2 weeks (Weeks 2, 4, 6, 8, and 10). Maintenance doses are expected to be completed over approximately 4-5 hours.

Follow-up visits will be on Weeks 12, 16, and 24. All subjects will be contacted by phone 6 months after study completion.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: ANX005 administered for up to 12 weeks
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2a Safety, Tolerability, Pharmacokinetic (PK), and Pharmacodynamic (PD) Study of Intravenous ANX005 in Subjects With Amyotrophic Lateral Sclerosis (ALS)
Estimated Study Start Date : November 15, 2020
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: ANX005

Induction dose of ANX005 IV (over 21-hour infusion) on Days 1 and 5 or 6 (5/6).

Maintenance dose of ANX005 IV (over 4-5 hour infusion) every 2 weeks (Weeks 2, 4, 6, 8, and 10).

Drug: ANX005
Induction Dose and Maintenance Dose




Primary Outcome Measures :
  1. Safety: Number of Participants Who Experienced Treatment-Emergent Adverse Events [ Time Frame: Up to week 12 ]
    Incidence and severity of treatment-emergent adverse events (AEs). AEs will be coded using MedDRA and severity of AEs will be graded using National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE).

  2. Pharmacokinetic: AUC(0-t) [ Time Frame: Blood samples collected predose to Day 5/6 after end of infusion on Day 1 and to EOS after Week 12 visit ]
    Area under the curve from time 0 to the last measurable observation. Blood samples will be obtained, and serum ANX005 concentrations determined using a validated ELISA method.

  3. Pharmacokinetic: AUC(0-inf) [ Time Frame: Blood samples collected predose to Day 5/6 after end of infusion on Day 1 and to EOS after Week 12 visit ]
    Area under the curve from time 0 to infinity.

  4. Pharmacokinetic: Cmax [ Time Frame: Blood samples collected predose to Day 5/6 after end of infusion on Day 1 and to EOS after Week 12 visit ]
    Maximum ANX005 serum concentration.

  5. Pharmacodynamic: C1q inhibition in CSF [ Time Frame: CSF samples collected predose and Week 12 ]
    CSF samples will be obtained to determine the amount of C1q. C1q will be measured using a validated enzyme-linked immunosorbent assay (ELISA) method.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects must meet all of the following criteria:

  1. Males or females aged 18 and above at the time of informed consent.
  2. Diagnosis of ALS according to the World Federation of Neurology revised E1 Escorial criteria.
  3. Onset of weakness within 3 years prior to enrollment.
  4. Slow Vital Capacity ≥ 60% of predicted normal adjusted for sex, age, and height (from the sitting position).
  5. Able to perform reproducible pulmonary function tests.
  6. ALS concomitant medications stable for at least 2 months prior to Screening.
  7. ALSFRS-R ≥ 30 at the Screening Visit.
  8. If female, must be postmenopausal, surgically sterilized, or agree to use highly effective methods of contraception from screening through Week 24.
  9. Males with a woman partner of childbearing potential must agree to use highly effective methods of contraception from Screening through Week 24.
  10. Documented history of vaccinations within 5 years prior to screening visit against encapsulated bacterial pathogens.
  11. Complete the full sequence of protocol related procedures and evaluations, including lumbar punctures for collection of cerebrospinal fluid.
  12. Ability to understand and provide written, informed consent.

Exclusion Criteria:

Subjects must not meet any of the following criteria:

  1. Clinically significant, ongoing illness or medical condition that would jeopardize the safety of the subject, limit participation, or compromise the interpretation of the safety data derived from the subject.
  2. Subjects with body weight > 150 kg.
  3. Clinically significant findings on screening laboratory testing, physical examination or vital signs that are not specific to ALS that could interfere with the conduct of the study, the interpretation of the data or increase subject risk.
  4. An ANA titer ≥ 1:160.
  5. History of previous infusion reactions, sensitivities, allergic, or anaphylactic reactions to previous medications, environmental stimuli or other substances.
  6. Receipt of an experimental agent within 60 days prior to Screening or through Week 24.
  7. Prior treatment with any monoclonal antibody within 6 months of screening.
  8. Hypersensitivity to any of the excipients in the ANX005 drug product.
  9. Clinically significant intercurrent illness, medical condition, or medical history that would jeopardize the safety of the subject, limit participation, or compromise the interpretation of the data derived from the subject.
  10. Any known genetic deficiencies of the complement-cascade system.
  11. History of chronic systemic steroid use or immunosuppressant medication ending less than 1 month prior to screening.
  12. Active alcohol, drug abuse or substance abuse.
  13. Females who are pregnant or unwilling to use highly effective methods of contraception.
  14. Contraindication to undergoing an LP.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04569435


Contacts
Layout table for location contacts
Contact: Maria Hernandez 650-822-5523 mhernandez@annexonbio.com
Contact: Marta Schumacher 650-822-5507 mschumacher@annexonbio.com

Locations
Layout table for location information
United States, California
Annexon Investigational Site 01
Irvine, California, United States, 92868
Contact: Maria Hernandez         
United States, Florida
Annexon Investigational Site 02
Gainesville, Florida, United States, 32608
Contact: Maria Hernandez         
Annexon Investigational Site 03
Tampa, Florida, United States, 33612
Contact: Maria Hernandez         
Sponsors and Collaborators
Annexon, Inc.
Worldwide Clinical Trials
Layout table for additonal information
Responsible Party: Annexon, Inc.
ClinicalTrials.gov Identifier: NCT04569435    
Other Study ID Numbers: ANX005-ALS-01
First Posted: September 29, 2020    Key Record Dates
Last Update Posted: October 20, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases