Phase 2 Study of Tanezumab in Subjects With Moderate to Severe Pain Due to Schwannomatosis

NCT04163419 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2019P003201
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine whether the administration of tanezumab, an anti-nerve growth factor (NGF) antibody, improves pain relief in schwannomatosis patients receiving background non-NSAID therapy.

Conditions

Schwannomatosis; Pain

Keywords

schwannoma; nerve growth factor; antibody; NGF

Outcome Measures

Primary Outcomes (1)

• Change in pain level

  Change in worst pain level during past week from baseline to week 8 measured by NRS-11

  8 weeks

Secondary Outcomes (2)

• Frequency of AEs

  40 weeks

• Incidence of orthostatic hypotension

  40 weeks

Study Arms (2)

Arm A (treatment)

EXPERIMENTAL

Tanezumab 10 mg SC administered on day 1 and Day 57 (± 4 days)

Drug: Tanezumab

Arm B (placebo then treatment)

PLACEBO COMPARATOR

Placebo SC (to match tanezumab SC) administered on Day 1 and tanezumab 10 mg SC on Day 57 (± 4 days)

Drug: Tanezumab; Drug: Placebo

Interventions

Tanezumab DRUG

Tanezumab 10 mg SC

Also known as: PF-04383119

Arm A (treatment); Arm B (placebo then treatment)

Placebo DRUG

Placebo 10 mg SC

Arm B (placebo then treatment)

Eligibility Criteria

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

You may qualify if:

• Patients must have a confirmed diagnosis schwannomatosis by fulfilling either clinical or molecular diagnosis.
• Age ≥ 18 years. Patients \< 18 years are excluded since the safety profile of tanezumab in this population has not been determined.
• ECOG performance status ≤2 or Karnofsky ≥60%
• Participants must have normal organ and marrow function as defined per the full protocol
• The subject's weight must be≥ 45 kg at Screening.
• The subject must be willing to avoid prohibited pain medications (including non-steroidal anti-inflammatory drugs) throughout the duration of the study except as permitted per Protocol.
• Subject must have moderate to severe pain secondary to schwannomatosis, defined as Score ≥5 on the Numeric Rating Scale-11 (NRS-11) at Screening.
• Subject must have failure, intolerance, or contraindication to at least three standard of care therapies:
• Documented history indicating that NSAID therapy has not provided adequate pain relief or subject is unable to take NSAIDs due to contraindication or inability to tolerate.
• Documented history indicating that opioid treatment has not provided adequate pain relief or subject is unwilling to take opioids, or unable to take opioids due to contraindication or inability to tolerate
• Documented history indicating that neuropathic pain medications, such as gabapentin, pregabalin, or others, have not provided adequate pain relief or subject is unable to take these treatments due to contraindication or inability to tolerate.
• Female subjects of childbearing potential and at risk for pregnancy (e.g., not abstinent) must agree to use 2 highly effective methods of contraception throughout the study and for 112 days (16 weeks) after the last dose of assigned subcutaneous study medication.

You may not qualify if:

• Subjects with any of the following criteria: evidence of bilateral vestibular schwannomas on imaging, a known germline pathogenic NF2 mutation, a first-degree relative who meets diagnostic criteria for NF2, or have schwannomas limited to a previous radiation field.
• Subjects who have had surgery, chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) for treatment of a painful schwannomatosis-related tumor prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Participation in other studies involving investigational drug(s) (Phases 1-4) within 30 days (or 90 days for biologics) before Screening and/or during study participation.
• Subjects receiving anticoagulation to treat an underlying medical condition.
• Subject has a history of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG fusion protein.
• The subject's pain is related to a non-schwannomatosis cause such as prior cancer therapy, infection, bowel obstruction/perforation, spinal cord compression, or fracture or impending fracture of weight bearing bone.
• The subject has a diagnosis of malignancy in the last 3 years (except for Gleason 6 prostate cancer, basal cell carcinoma or carcinoma in situ).
• Use of concurrent adjuvant analgesics such as serotonin norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants, anticonvulsant medication, or muscle relaxants (unless the drugs were started at least 30 days prior to Screening and are maintained at a stable dose).
• Use of concurrent analgesic non-steroidal anti-inflammatory drugs (NSAIDs, including selective COX-2 inhibitors) unless the subject is expected to be able to discontinue these medications at least 2 weeks prior to treatment. Note: Subjects who take daily low dose aspirin (≤ 325 mg as per local prescribing practice) therapy for cardiovascular prophylaxis are not excluded from participation.
• Diagnosis of osteoarthritis of the knee or hip as defined by the American College of Rheumatology (ACR) combined clinical and radiographic criteria; Radiographic criteria will be assessed by the Central Reader.
• Use of concurrent corticosteroids (except for inhaled or topical corticosteroids as needed for management of ongoing pulmonary or dermatologic conditions)
• Subjects considered unfit for surgery, defined as Grade \>3 on the American Society of Anesthesiologists (ASA) physical classification system for surgery or subjects who would not be willing to undergo joint replacement surgery if required.
• Subjects with symptoms and radiographic findings (i.e. joint space narrowing, osteophytes) consistent with osteoarthritis in the shoulder.
• History of significant trauma or surgery to a major joint (e.g. hip, knee or shoulder) within one year prior to Screening.
• A history of osteonecrosis or osteoporotic fracture (i.e., a subject with a history of osteoporosis and a minimally traumatic or atraumatic fracture).

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Pfizer: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Da JLW, Merker VL, Jordan JT, Ly KI, Muzikansky A, Parsons M, Wolters PL, Xu L, Styren S, Brown MT, Plotkin SR. Design of a randomized, placebo-controlled, phase 2 study evaluating the safety and efficacy of tanezumab for treatment of schwannomatosis-related pain. Contemp Clin Trials. 2022 Oct;121:106900. doi: 10.1016/j.cct.2022.106900. Epub 2022 Aug 26.

  PMID: 36038003 DERIVED

MeSH Terms

Conditions

Schwannomatosis; Pain; Neurilemmoma; Hereditary Sensory and Autonomic Neuropathies

Interventions

tanezumab

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Scott R Plotkin

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: November 12, 2019
• First Posted: November 14, 2019
• Study Start: April 30, 2020
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2024
• Last Updated: March 13, 2024

Record last verified: 2024-03

Locations

US (1)