A First-in-human, Single Ascending Dose Study of GZ402668 in Patients With Progressive Multiple Sclerosis

NCT02282826 | Completed Phase 1

• 3 other identifiers: TDU134752014-001591-61U1111-1155-6252
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To assess the safety and tolerability of GZ402668 after ascending single intravenous (IV) and subcutaneous (SC) doses in men and women with progressive multiple sclerosis. Secondary Objectives: To assess the following in men and women with progressive multiple sclerosis:

• The pharmacokinetic (PK) parameters of GZ402668 after ascending single IV doses.
• The pharmacodynamics (PD) of GZ402668 after ascending single IV doses.
• The PK parameters of GZ402668 after ascending single SC doses.
• The PD of GZ402668 after ascending single SC doses.

Conditions

Progressive Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment emergent adverse events

  4 weeks

Secondary Outcomes (6)

• maximum concentration (Cmax)

  4 weeks

• area under curve (AUC)

  4 weeks

• Number of participants with lymphocyte depletion

  4 weeks

• Number of participants with anti-drug antibodies

  4 weeks

• Number of participants with injection site reactions

  2 weeks

Study Arms (8)

Dose 1 IV

EXPERIMENTAL

GZ402668 dose 1 intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

Drug: GZ402668; Drug: acyclovir

Dose 2 IV

EXPERIMENTAL

GZ402668 dose 2 intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

Drug: GZ402668; Drug: acyclovir

Dose 3 IV

EXPERIMENTAL

GZ402668 dose 3 intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

Drug: GZ402668; Drug: acyclovir

Dose 3 SC

EXPERIMENTAL

GZ402668 dose 3 subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

Drug: GZ402668; Drug: acyclovir

Dose 4 SC

EXPERIMENTAL

GZ402668 dose 4 subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

Drug: GZ402668; Drug: acyclovir

Dose 5 SC

EXPERIMENTAL

GZ402668 dose 5 subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

Drug: GZ402668; Drug: acyclovir

Placebo SC

PLACEBO COMPARATOR

placebo subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

Drug: placebo; Drug: acyclovir

Placebo IV

PLACEBO COMPARATOR

placebo intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

Drug: placebo; Drug: acyclovir

Interventions

GZ402668 DRUG

Pharmaceutical form:solution Route of administration: intravenous

Dose 1 IV; Dose 2 IV; Dose 3 IV

placebo DRUG

Pharmaceutical form:solution Route of administration: intravenous

Placebo IV

acyclovir DRUG

Pharmaceutical form:tablet Route of administration: oral

Dose 1 IV; Dose 2 IV; Dose 3 IV; Dose 3 SC; Dose 4 SC; Dose 5 SC; Placebo IV; Placebo SC

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female adult with a diagnosis of progressive multiple sclerosis (MS) including primary progressive MS, secondary progressive MS, and progressive relapsing MS.
• Aged between 18 and 65 years, inclusive.
• Body weight greater than 40.0 kg.
• Female patient of child bearing potential must use 2 highly effective contraception methods.
• Male patient who has agreed not to donate sperm for 4 months after product administration.

You may not qualify if:

• Significant medical diseases or conditions, including poorly controlled hypertension, cardiovascular disease, inflammatory disorders, immunodeficiency, autoimmune disease, renal failure, liver dysfunction, cancer (except treated basal skin cell carcinoma), or active infection.
• Frequent headaches and/or migraine, recurrent nausea and/or vomiting.
• History or presence of drug or alcohol abuse.
• Smoking more than 5 cigarettes or equivalent per day.
• If female, pregnancy, lactating, or breast-feeding.
• Patients with relapsing-remitting MS.
• Lymphocyte counts below the lower limit of normal.
• Treatment with natalizumab, methotrexate, azathioprine, or cyclosporine in the past 6 months.
• Treatment with mitoxantrone, cyclophosphamide, cladribine, rituximab or any other immunosuppressant or cytotoxic therapy (other than steroids) in the last 12 months, or determined by the treating physician to have residual immune suppression from these treatments.
• Treatment with glatiramer acetate or interferon beta in the past 4 weeks.
• Treatment with fingolimod within the past 2 months.
• Treatment with dimethyl fumarate in past 4 weeks.
• Treatment with teriflunomide within the past 12 months unless patient has completed an accelerated clearance with cholestyramine.
• Previous treatment with alemtuzumab.
• Live, attenuated vaccine within 3 months prior to the randomization visit, such as varicella-zoster, oral polio, and rubella vaccines.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (1)

Investigational Site Number 276001

Berlin, 10117, Germany

Location

Related Publications (1)

• Albach FN, Geier C, Keicher C, Posch MG, Schreiber SJ, Grutz G, Akyuz L, Luo X, Le-Halpere A, Truffinet P, Wagner F. Phase 1 Trials of Gatralimab, a Next-Generation Humanized Anti-CD52 Monoclonal Antibody, in Participants with Progressive Multiple Sclerosis. Neurol Ther. 2024 Dec;13(6):1607-1625. doi: 10.1007/s40120-024-00659-w. Epub 2024 Sep 9.

  PMID: 39251561 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

Acyclovir

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2014
• First Posted: November 4, 2014
• Study Start: October 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: April 13, 2016

Record last verified: 2016-04

Locations

DE (1)