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

Brief Title

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

Official Title

A Phase 2 Randomized, Double-blind, Placebo-Controlled Study of the Analgesic Efficacy and Safety of the Subcutaneous Administration of the Anti-NGF Antibody Tanezumab in Subjects With Moderate to Severe Pain Due to Schwannomatosis

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.
    

Detailed Description

      Schwannomatosis is characterized by the predisposition to develop multiple schwannomas and,
      less commonly, meningiomas. Pain is the most frequent symptom reported by these patients,
      with 68% experiencing chronic pain.

      The investigators propose to test the efficacy and tolerability of tanezumab as a treatment
      for schwannomatosis patients with chronic pain who have had inadequate pain relief in a
      randomized, placebo-controlled trial, which could form the basis of a larger, randomized
      controlled trial in the future.

      The study is designed with a total duration of 281 days (40 weeks) and will consist of four
      periods: Pre-treatment, Double-Blind Treatment, Single Arm Treatment, and 24-Week Safety
      Follow-up. The Pre-Treatment Period lasting up to 30 days, followed by a Double-Blind
      Treatment Period lasting up to 8 weeks, followed by a Single Arm Treatment Period lasting up
      to 8 weeks, and a 24-Week Safety Follow-Up Period ending with the End of Study Visit at Week
      40.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Change in pain level

Secondary Outcome

 Frequency of AEs

Condition

Schwannomatosis

Intervention

Tanezumab

Study Arms / Comparison Groups

 Arm A (treatment)
Description:  Tanezumab 10 mg SC administered on day 1 and Day 57 (± 4 days)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

46

Start Date

April 30, 2020

Completion Date

June 2024

Primary Completion Date

June 2023

Eligibility Criteria

        Inclusion Criteria:

          1. Patients must have a confirmed diagnosis schwannomatosis by fulfilling either clinical
             or molecular diagnosis.

          2. Age ≥ 18 years. Patients < 18 years are excluded since the safety profile of tanezumab
             in this population has not been determined.

          3. ECOG performance status ≤2 or Karnofsky ≥60%

          4. Participants must have normal organ and marrow function as defined per the full
             protocol

          5. The subject's weight must be≥ 45 kg at Screening.

          6. 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.

          7. Subject must have moderate to severe pain secondary to schwannomatosis, defined as
             Score ≥5 on the Numeric Rating Scale-11 (NRS-11) at Screening.

          8. 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.

          9. 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.

        Exclusion Criteria:

          1. 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.

          2. Subjects with intracranial meningioma associated with cerebral edema on neuroimaging.
             Note: presence of intracranial meningioma itself is not an exclusion criterion.

          3. 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.

          4. 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.

          5. Subjects receiving anticoagulation to treat an underlying medical condition.

          6. Subject has a history of allergic or anaphylactic reaction to a therapeutic or
             diagnostic monoclonal antibody or IgG fusion protein.

          7. 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.

          8. 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).

          9. 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).

         10. 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.

         11. 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.

         12. Use of concurrent corticosteroids (except for inhaled or topical corticosteroids as
             needed for management of ongoing pulmonary or dermatologic conditions)

         13. 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.

         14. Subjects with symptoms and radiographic findings (i.e. joint space narrowing,
             osteophytes) consistent with osteoarthritis in the shoulder.

         15. History of significant trauma or surgery to a major joint (e.g. hip, knee or shoulder)
             within one year prior to Screening.

         16. A history of osteonecrosis or osteoporotic fracture (i.e., a subject with a history of
             osteoporosis and a minimally traumatic or atraumatic fracture).

         17. Radiographic (x-ray) evidence of any of the following conditions as determined by the
             central radiology reviewer at Screening: 1) rapidly progressive osteoarthritis, 2)
             atrophic or hypotrophic osteoarthritis, 3) subchondral insufficiency fracture, 4)
             spontaneous osteonecrosis of the knee (SPONK), 5) osteonecrosis, or 6) pathologic
             fracture.

         18. Subjects who have evidence of orthostatic hypotension based upon replicate orthostatic
             blood pressure measurements at Screening.

         19. Subjects with a total impact score of >7 on the Survey of Autonomic Symptoms (SAS) at
             Screening.

         20. Diagnosis of a transient ischemic attack in the 6 months prior to Screening or
             diagnosis of stroke with residual deficits (e.g., aphasia, substantial motor or
             sensory deficits), that would preclude completion of required study activities.

         21. History, diagnosis, or signs and symptoms of clinically significant neurological

         22. Subjects with a past history of carpal tunnel syndrome (CTS) with signs or symptoms of
             CTS in the one year prior to Screening.

         23. Subject with a history of significant alcohol, analgesic, or narcotic substance abuse
             within the six months prior to Screening.

         24. Subject who, in the judgement of the investigator, is expected to require a surgical
             procedure during the duration of the study.

         25. Previous exposure to exogenous nerve growth factor or to an anti-nerve growth factor
             antibody.

         26. Subjects who are investigational site staff members directly involved in the conduct
             of the trial and their family members, site staff members otherwise supervised by the
             Investigator, or subjects who are Pfizer employees directly involved in the conduct of
             the trial

         27. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

         28. Pregnant females; breastfeeding females; females of childbearing potential not using
             two (2) methods of highly effective contraception or not agreeing to continue two (2)
             methods of highly effective contraception for 112 days (16 weeks) after last dose of
             investigational product.

         29. Any subject who, in the judgement of the investigator, is deemed inappropriate for
             participation in the study.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Scott R Plotkin, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04163419

Organization ID

2019P003201


Responsible Party

Principal Investigator

Study Sponsor

Massachusetts General Hospital

Collaborators

 Pfizer

Study Sponsor

Scott R Plotkin, Principal Investigator, Massachusetts General Hospital


Verification Date

April 2020